Research Liver Disease
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Long-Term Zinc Supplementation Improves Liver Function and Decreases the Risk of Developing Hepatocellular Carcinoma
Atsushi Hosui *, Eiji Kimura, Sumiko Abe, Takashi Tanimoto, Kousaku Onishi, Yukihiro Kusumoto, Yuka Sueyoshi, Kengo Matsumoto, Motohiro Hirao, Takuya Yamada and Naoki Hiramatsu
Abstract
Zinc plays a pivotal role in various zinc enzymes, which are crucial in the maintenance of liver function. Patients with chronic liver diseases (CLDs) usually have lower concentrations of zinc, which decrease further as liver fibrosis progresses. Whether long-term zinc supplementation improves liver function and reduces the risk of hepatocellular carcinoma (HCC) development remains unknown. Two hundred and sixty-seven patients with CLDs who received a zinc preparation (Zn-group; 196 patients), or who did not receive zinc (no Zn-treatment group; 71 patients), were retrospectively analyzed in this study. The Zn-group was divided into 4 groups according to their serum Zn concentrations at 6 months after the start of Zn treatment. Liver function significantly deteriorated in the no Zn-treatment group, while no notable change was observed in the Zn-group. The cumulative incidence rates of events and HCC at 3 years were observed to be lower in the Zn-group (9.5%, 7.6%) than in the no Zn-treatment group (24.9%, 19.2%) (p < 0.001). According to serum Zn concentrations, the cumulative incidence rates of events and HCC were significantly decreased in patients with Zn concentrations ≥ 70 µg/dL (p < 0.001). Zinc supplementation appears to be effective at maintaining liver function and suppressing events and HCC development, especially among patients whose Zn concentration is greater than
70 µg/dL.
Source : Journal Nutrients
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A network pharmacology-based study on the anti-hepatoma effect of Radix Salviae Miltiorrhizae
Yi Luo, Yu Feng, Lei Song, Gan-Qing He, Sha Li, Sha-Sha Bai, Yu-Jie Huang, Si-Ying Li, Mohammed M. Almutairi, Hong-Lian Shi, Qi Wang & Ming Hong
Abstract
Background
Radix Salviae Miltiorrhizae (RSM), a well-known traditional Chinese medicine, has been shown to inhibit tumorigenesis in various human cancers. However, the anticancer effects of RSM on human hepatocellular carcinoma (HCC) and the underlying mechanisms of action remain to be fully elucidated.
Methods
In this study, we aimed to elucidate the underlying molecular mechanisms of RSM in the treatment of HCC using a network pharmacology approach. In vivo and in vitro experiments were also performed to validate the therapeutic effects of RSM on HCC.
Results
In total, 62 active compounds from RSM and 72 HCC-related targets were identified through network pharmacological analysis. RSM was found to play a critical role in HCC via multiple targets and pathways, especially the EGFR and PI3K/AKT signaling pathways. In addition, RSM was found to suppress HCC cell proliferation, and impair cancer cell migration and invasion in vitro. Flow cytometry analysis revealed that RSM induced cell cycle G2/M arrest and apoptosis, and western blot analysis showed that RSM up-regulated the expression of BAX and down-regulated the expression of Bcl-2 in MHCC97-H and HepG2 cells. Furthermore, RSM administration down-regulated the expression of EGFR, PI3K, and p-AKT proteins, whereas the total AKT level was not altered. Finally, the results of our in vivo experiments confirmed the therapeutic effects of RSM on HCC in nude mice.
Conclusions
We provide an integrative network pharmacology approach, in combination with in vitro and in vivo experiments, to illustrate the underlying therapeutic mechanisms of RSM action on HCC.
Source : Journal Chinese Medicine
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Coffee prevents fatty liver disease induced by a high-fat diet by modulating pathways of the gut–liver axis
Paola Vitaglione (a1) (a2), Giovanna Mazzone (a3), Vincenzo Lembo (a3), Giuseppe D'Argenio (a3)
Abstract
Coffee consumption is inversely associated with the risk of non-alcoholic fatty liver disease (NAFLD). A gap in the literature still exists concerning the intestinal mechanisms that are involved in the protective effect of coffee consumption towards NAFLD. In this study, twenty-four C57BL/6J mice were divided into three groups each receiving a standard diet, a high-fat diet (HFD) or an HFD plus decaffeinated coffee (HFD+COFFEE) for 12 weeks. Coffee supplementation reduced HFD-induced liver macrovesicular steatosis (P < 0·01) and serum cholesterol (P < 0·001), alanine aminotransferase and glucose (P < 0·05). Accordingly, liver PPAR- α(P < 0·05) and acyl-CoA oxidase-1 (P < 0·05) as well as duodenal ATP-binding cassette (ABC) subfamily A1 (ABCA1) and subfamily G1 (ABCG1) (P < 0·05) mRNA expressions increased with coffee consumption. Compared with HFD animals, HFD+COFFEE mice had more undigested lipids in the caecal content and higher free fatty acid receptor-1 mRNA expression in the duodenum and colon. Furthermore, they showed an up-regulation of duodenal and colonic zonulin-1 (P < 0·05), duodenal claudin (P < 0·05) and duodenal peptide YY (P < 0·05) mRNA as well as a higher abundance of Alcaligenaceae in the faeces (P < 0·05). HFD+COFFEE mice had an energy intake comparable with HFD-fed mice but starting from the eighth intervention week they gained significantly less weight over time. Data altogether showed that coffee supplementation prevented HFD-induced NAFLD in mice by reducing hepatic fat deposition and metabolic derangement through modification of pathways underpinning liver fat oxidation, intestinal cholesterol efflux, energy metabolism and gut permeability. The hepatic and metabolic benefits induced by coffee were accompanied by changes in the gut microbiota.
Source : Journal of Nutritional Science
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A Compound of Chinese Herbs Protects against Alcoholic Liver Fibrosis in Rats via the TGF-β1/Smad Signaling Pathway
Xiaomeng Li,1,2 Yunjie Liu,1,2 Wuyang Yue,1,2 Yuefeng Tan,1,2 He Wang,1,2Lishi Zhang,1,2 and Jinyao Chen
Abstract
Alcoholic liver fibrosis (ALF) has become a major public health concern owing to its health impacts and the lack of effective treatment strategies for the disease. In this study, we investigated the effect of a compound composed of Chinese herbs Pueraria lobata (Willd.), Salvia miltiorrhiza, Schisandra chinensis, and Silybum marianum on ALF. An ALF model was established. Rats were fed with modified Lieber–Decarli alcohol liquid diet and injected with trace CCl4 at late stage. The rats were then treated with several doses of the compound. Biochemical and fibrosis-relevant parameters were measured from the sera obtained from the rats. Liver tissues were obtained for hematoxylin and eosin and Masson’s trichrome staining. Matrix metalloproteinase-13 and tissue inhibitor of metalloproteinase-1 were determined by immunohistochemistry assays. The mRNA and protein expression levels of transforming growth factor-β1 (TGF-β1), Smad2, Smad3, and Smad7 on the livers were also measured by quantitative polymerase chain reaction and Western blot. Results showed that the compound treatment alleviated pathological lesions in the liver, decreased the serum levels of hyaluronan, laminin, and hydroxyproline, and diminished the expression of hepatic tissue inhibitor of metalloproteinase-1. Compound treatment also increased hepatic matrix metalloproteinase-13 expression and inhibited the TGF-β1/Smad signaling pathway. In conclusion, the compound has a protective effect against ALF in rats, and an underlying mechanism is involved in the TGF-β1/Smad signaling pathway.
Source Journal Evidence Based Complementary and Alternative Medicine
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Coffee consumption and liver-related hospitalizations and deaths in the ARIC study
Emily A. Hu, Mariana Lazo, Elizabeth Selvin, James P. Hamilton, Morgan E. Grams, Lyn M. Steffen, Josef Coresh & Casey M. Rebholz
Abstract
Background/Objectives
Coffee consumption has been found to be associated with reduced risk of chronic conditions such as liver disease. However, less is known about the association between coffee and liver-related hospitalizations and deaths.
Subjects/Methods
We conducted a prospective analysis on 14,208 participants aged 45–64 years from the Atherosclerosis Risk in Communities (ARIC) study. Coffee consumption (cups/day) was assessed using food frequency questionnaires at visit 1 (1987–89) and visit 3 (1993–95). Liver-related hospitalizations were defined as a hospitalization with any International Classification of Diseases, Ninth Revision (ICD-9) code related to liver disease identified through cohort surveillance. Liver-related death was defined as any death with a liver disease ICD-9 code listed anywhere on the death certificate form.
Results
There were 833 incident cases of liver-related hospitalizations over a median follow-up of 24 years and 152 liver-related deaths over a median follow-up of 25 years. Participants who were in the highest category of coffee consumption (≥ 3 cups/day) were more likely to be men, whites, current smokers, and current alcohol drinkers. In our fully adjusted model, consuming ≥ 3 cups/day of coffee was significantly associated with a reduced risk of liver-related hospitalizations compared with never drinkers (hazard ratio: 0.79, 95% CI: 0.63–0.99). There were no significant associations between coffee consumption and liver-related deaths after adjusting for covariates.
Conclusions
Coffee drinkers may be at lower risk for liver-related hospitalizations. This supports current evidence that low and moderate levels of coffee may be protective to the liver.
Source: European Journal of Clinical Nutrition
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Curcumin attenuates hepatic fibrosis and insulin resistance induced by bile duct ligation in rats
Azam Eshaghian1 , Ameneh Khodarahmi1 , Fatemeh Safari2 , Fariba Binesh3 and Ali Moradi1 *
1 Department of Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, 8915173149, Iran
2 Department of Physiology, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, 8915173149, Iran
3 Department of Pathology, Shahid Sadoughi University of Medical Sciences, Yazd, 8915173149, Iran
Abstract
Recent studies have strongly indicated the hepatoprotective effect of curcumin; however, the precise mechanisms are not well understood. This study aimed to determine the protective effect of curcumin on hepatic damage and hepatic insulin resistance in biliary duct ligated (BDL) fibrotic rat model. To accomplish this, male Wistar rats were divided into four groups (eight for each): sham group, BDL group, sham + Cur group and BDL + Cur group. The last two groups received curcumin at a dose of 100 mg/kg daily for 4 weeks. The mRNA/protein expression levels of Ras-related C3 botulinum toxin substrate 1 (Rac1), Rac1-GTP, dinucleotide phosphate oxidase 1 (NOX1), signal transducer and activator of transcription 3 (STAT3), suppressor of cytokine signalling 3 (SOCS3), insulin receptor substrate 1 (IRS1), extracellular signalregulated kinase 1 (ERK1), specific protein 1 (Sp1) and hypoxia-inducible factor-1α (HIF-1α) were measured by real-time PCR and Western blotting, respectively. Fasting blood glucose, insulin and Leptin levels were determined and homoeostasis model assessment-estimated insulin resistance, as an index of insulin resistance, was calculated. Curcumin significantly attenuated liver injury and fibrosis, including amelioration of liver histological changes, reduction of hepatic enzymes, as well as decreased expression of liver fibrogenesis-associated variables, including Rac1, Rac1-GTP, NOX1, ERK1, HIF-1α and Sp1. Curcumin also attenuated leptin level and insulin resistance, which had increased in BDL rats (P<0·05). Furthermore, compared with the BDL group, we observed an increase in IRS1 and a decrease in SOCS3 and STAT3 expression in the curcumin-treated BDL group (P <0·05), indicating return of these parameters towards normalcy.
therapeutic option.
Source : British Journal of Nutrition via Sci-hub
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Protective effects of saffron extract and crocin supplementation on fatty liver tissue of high-fat diet-induced obese rats
Abstract
Background Saffron is the dried stigma of Crocus sativus L. flower which commonly used as a natural remedy to enhance health and even fights disease in the Middle-East and Southeast Asian countries.
Methods This study was aimed to investigate protective effect of saffron extract and crocin in fatty liver tissue of high-fat diet induced obese rats. A total of 36 healthy male Sprague Dawley rats were divided into six groups. Two groups served as controls, a normal diet (ND) and a high-fat diet (HFD). The other four groups were each supplemented with saffron extract and crocin at concentrations of 40 and 80 mg/kg body weight/day for 8 weeks. All groups except ND were fed with HFD until end of the study. At baseline, blood sample was collected for determination of levels of hepatic marker enzymes, including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatise and albumin. Liver sample was collected, weighed and stained with haematoxylin and eosin for further histopathological examination.
Results Saffron extract and crocin at concentrations of 40 and 80 mg/kg had dose-dependently alleviated levels of liver enzymes and histopathological changes in diet-induced obese rat model compared to control (HFD group).
Conclusion This study suggested that saffron extract and crocin supplements have hepatoprotective effect against non-alcoholic fatty liver disease and HFD-induced liver damage.
Source : BMC Complementary and Alternative Medicine
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The Therapeutic Effect of Berberine in the Treatment of Nonalcoholic Fatty Liver Disease: A Meta-Analysis
Xiaoyun Wei,1 Chunyan Wang,1 Shijun Hao,1 Haiyan Song,1,2 and Lili Yang1,2
1Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
2China-Canada Center of Research for Digestive Diseases (ccCRDD), Shanghai 200032, China
Abstract
Aim. To assess the efficacy of berberine in the treatment of nonalcoholic fatty liver disease through meta-analysis.
Method. We searched Embase, Pubmed, Cochrane Library, and so forth, until March 2016 for randomized controlled trials using berberine to treat NAFLD.
Result. Six randomized controlled trials involving 501 patients were included in this study. The results showed that the efficacy of reducing TC, LDL, ALT, 2hPG, and HbA1c in NAFLD patients of the berberine group were significantly higher than that of control group. The subgroup analyses on TG, AST, and FBG indicated that treatment combined with berberine decreased TG level in NAFLD patients significantly. Compared with other drugs, berberine alone decreased TG level in NAFLD patients significantly. We also conducted a descriptive analysis on insulin resistance and radiography results that berberine can improve NAFLD patients’ insulin resistance and fatty liver.
Conclusion. According to analysis result, berberine has positive efficacy on blood lipids, blood glucose, liver function, insulin resistance, and fatty liver condition of NAFLD patients. However, due to the limitation of number and quality of trials included, more clinical randomized controlled trials with high quality are needed for further verification of the efficacy of berberine on NAFLD patients.
Source : Journal Evidence Based Complementary and Alternative Medicine
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Immunomodulation and liver protection of Yinchenhao decoction against concanavalin A-induced chronic liver injury in mice
1.Shi-li Jiang (Department of Liver Cirrhosis, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China )
2.Xu-dong Hu (Department of Biology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China )
3.Ping Liu (E-institute of Shanghai Municipal Education Committee, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China )
ABSTRACT
OBJECTIVE: This study investigated the immunoregulatory and protective roles of Yinchenhao decoction, a compound of Chinese herbal medicine, in a mouse model of concanavalin A (ConA)-induced chronic liver injury.
METHODS: Female BalB/c mice were randomly divided into 4 groups: normal control, ConA model, ConA model treated with Yinchenhao decoction (400 mg/kg, orally), and ConA model treated with dexamethasone (0.5 mg/kg, orally). All treatments were given once a day for 28 d. Except of the normal control, mice received tail vein injection of ConA (10 mg/kg) on days 7, 14, 21, and 28, at 1 h after treatment with Yinchenhao decoction or dexamethasone or saline to induce chronic liver injury.
RESULTS: Repeated ConA injection induced chronic liver injury, which was evidenced by inflammatory cell infiltration and necrosis, increased serum alanine aminotranferease activities, decreased albumin levels, and an imbalanced expression of immunoregulatory genes in the liver tissues including significantly enhanced interferon-γ, interleukin-4, monocyte chemotactic protein-1, and cluster of differentiation 163 mRNA levels, and reduced tumor necrosis factor-α and interleukin-6 mRNA levels. Treatment with Yinchenhao decoction significantly reversed the ConA-induced changes in immunoregulatory gene expression in the liver tissues, reduced serum alanine aminotranferease activity, enhanced serum albumin level, and attenuated the extent of liver inflammation and necrosis. Furthermore, Yinchenhao decoction did not result in hepatocyte degeneration and spleen weight loss that were observed in mice received long-term treatment with dexamethasone.
CONCLUSION: Yinchenhao decoction treatment protected liver against the ConA-induced chronic liver damage and improved liver function, which were associated with the modulation of gene expression related to immune/inflammatory response.
Source : Journal Integrative Medicine
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Protective activity of kudzu (Pueraria thunbergiana) vine on chemically-induced hepatotoxicity: in vitro and in vivo studies
Abstract
Background
Kudzu (Pueraria thunbergiana) root has long been used in Traditional Chinese Medicine. However, the vine of the kudzu plant has been considered waste material. This study aimed to investigate the hepatoprotective properties of the kudzu vine.
Methods
We created 0 %, 30 %, 70 %, and 95 % ethanolic kudzu vine extracts. The isoflavone contents of kudzu vine extract were quantified by high-performance liquid chromatography. Tertiary-butylhydroperoxide (t-BHP) was added to human liver-derived HepG2 cells, and the production of reactive oxygen species was measured in the presence and absence of kudzu vine extract. Antioxidant activity was evaluated in all kudzu vine extracts using a hydroxyradical scavenging assay. Thirty-five male Sprague–Dawley rats were divided into seven groups (n = 5); two groups were not given any extract or drug, one group was treated with 50 mg/kg silymarin orally for 5 days, and the remaining four groups were respectively treated with 100 mg/kg of 0 %, 30 %, 70 %, or 95 % ethanolic extract of kudzu vine orally once daily for 5 days. On day 5 the treatment groups and one untreated group were fed 0.75 ml/kg carbon tetrachloride (CCl4) to induce liver damage. Blood and liver tissue samples were collected 24 h after CCl4 administration for measurement of plasma alanine aminotransferase and aspartate aminotransferase, and concentration of malondialdehyde and glutathione in liver tissue.
Results
Puerarin was the most abundant isoflavone in kudzu vine extract. Kudzu vine extract significantly reduced the cytotoxicity and production of reactive oxygen species induced by t-BHP in a dose-dependent manner. Treatment with 0 % and 30 % ethanolic extracts of kudzu vine significantly lowered the plasma levels of alanine aminotransferase and aspartate aminotransferase in a CCl4-induced hepatotoxicity rat model (P < 0.05). Glutathione was significantly elevated in the 30 % ethanolic extract-treated group (P < 0.05), while the malondialdehyde level in liver tissue was significantly decreased in the 0 % and 30 % ethanolic extract-treated groups (P < 0.05).
Conclusions
The kudzu vine is potentially highly beneficial in treating liver damage, as it scavenges reactive free radicals and boosts the endogenous antioxidant system.
Source : BMC Complementary and Alternative Medicine
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Hepatoprotective effect of licorice, the root of Glycyrrhiza uralensis Fischer, in alcohol-induced fatty liver disease
Abstract
Background
Our previous study suggested that licorice has anti-inflammatory activity in lipopolysaccharide-stimulated microglial cells and anti-oxidative activity in tert-butyl hydroperoxide–induced oxidative liver damage. In this study, we evaluated the effect of licorice on chronic alcohol-induced fatty liver injury mediated by inflammation and oxidative stress.
Methods
Raw licorice was extracted, and quantitative and qualitative analysis of its components was performed by using LC–MS/MS. Mice were fed a liquid alcohol diet with or without licorice for 4 weeks.
Results
We have standardized 70 % fermented ethanol extracted licorice and confirmed by LC-MS/MS as glycyrrhizic acid (GA), 15.77 ± 0.34 μg/mg; liquiritin (LQ), 14.55 ± 0.42 μg/mg; and liquiritigenin (LG), 1.34 ± 0.02 μg/mg, respectively. Alcohol consumption increased serum alanine aminotransferase and aspartate aminotransferase activities and the levels of triglycerides and tumor necrosis factor (TNF)-α. Lipid accumulation in the liver was also markedly induced, whereas the glutathione level was reduced. All these alcohol-induced changes were effectively inhibited by licorice treatment. In particular, the hepatic glutathione level was restored and alcohol-induced TNF-α production was significantly inhibited by licorice.
Conclusion
Taken together, our data suggests that protective effect of licorice against alcohol-induced liver injury may be attributed to its anti-inflammatory activity and enhancement of antioxidant defense.
Source : BMC Evidence Based Complementary and Alternative Medicine
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Coffee and Caffeine Intake Are Associated with Lower Risk for Advanced Hepatic Fibrosis in Patients with Hepatitis C
Khalaf N, White D, Kanwal F, et al. Coffee and caffeine are associated with decreased risk of advanced hepatic fibrosis among patients with hepatitis C. Clin Gastroenterol Hepatol. August 2015;13(8):1521-1531.e3.
One of the most popular beverages worldwide, the consumption of coffee (Coffea arabica, Rubiaceae) is associated with a number of health benefits, including protection against the development of liver injury (hepatoprotection). Also, there is an inverse association between coffee consumption and hepatocellular carcinoma with or without chronic hepatitis C virus (HCV) infection. These authors used data from a cross-sectional study among U.S. veterans with chronic HCV infection to investigate the association between caffeinated and decaffeinated coffee, tea (Camellia sinensis, Theaceae), and soda intake and the development of HCV-related advanced liver fibrosis. Their secondary objective was to determine the extent to which insulin resistance mediates the association between caffeine intake and the severity of liver fibrosis.
The study was conducted at the Michael E. DeBakey Veterans Affairs Medical Center in Houston, Texas. Participants were veterans aged 18 to 70 years with confirmed HCV viremia who were prospectively recruited from a dedicated HCV clinic at the medical center between January 5, 2009 and November 30, 2013. The participants were not receiving antiviral therapy at the time of recruitment.
At baseline and after 12 weeks, participants underwent fasting blood draws for clinical laboratory tests, had anthropometric measurements taken, and body mass index (BMI) scores calculated. They completed a detailed questionnaire about their lifetime use of alcohol, tobacco (Nicotiana tabacum, Solanaceae), injection drugs, marijuana (Cannabis sativa, Cannabaceae), and other recreational drugs, as well as the presence of comorbid conditions, such as diabetes mellitus. All participants were scored using the Model for End-Stage Liver Disease (MELD) instrument, which assesses the severity of chronic liver disease.
The participants also provided information on their intake of caffeinated and decaffeinated coffee, tea, and carbonated soda, and their use of creamers and sweeteners. Cumulative lifetime exposure to coffee was determined by their reported daily intake in each decade of life starting with the 20s. For assessing average caffeine content, the authors estimated 137 mg for each 8 oz cup of coffee, 30 mg for each 8 oz cup of tea, 46 mg for each 12 oz can of caffeinated soda, and 0 mg for decaffeinated beverages.
The exposure variables were caffeinated and decaffeinated coffee intake, tea intake, and soda intake, and caffeine intake overall and from each beverage. The main outcome variable was advanced hepatic fibrosis as scored by using the FibroSURE test, which estimates the level of liver fibrosis and inflammation.
The study included 910 veterans with chronic HCV infection. Based on FibroSURE scores, 342 (37.6%) had advanced fibrosis (AF); the remaining 568 (62.4%) with mild fibrosis served as controls for the analysis. Most of the participants were male (98%), African-American, and chronic alcohol users. Those with AF were older (average, +1.8 years), had a higher BMI, and were more likely to have type 2 diabetes mellitus, metabolic syndrome, and higher MELD scores than the controls. Among nondiabetic participants, AF cases were more likely than controls to be insulin resistant based on a baseline fasting homeostasis model assessment-insulin resistance (HOMA-IR) score of ≥ 3. They were also more likely to have received prior HCV antiviral therapy. Though none were receiving treatment at the time of the study, all participants had detectable HCV RNA levels, confirming the presence of HCV in the blood.
In terms of liver inflammation, 252 participants (27.7%) were classified as advanced inflammatory activity cases and 658 (72.3%) were classified as mild inflammatory activity controls based on FibroSURE scores. There was no association between caffeine intake and severity of inflammation.
Most participants (54.6%) reported drinking some caffeinated coffee within the year before the study, with 47.2% drinking 1 or more cups daily. The controls had a higher average daily intake of caffeinated coffee compared with the AF cases (P=0.038) and more controls than AF cases reported drinking an average of 1 or more cups daily (P=0.045).
About 70% of participants reported drinking caffeinated tea within the preceding year; 22.7% consumed 1 or more cups daily. Tea intake, both caffeinated and decaffeinated, was not significantly different between the AF cases and controls. However, among the 413 non-coffee drinkers, caffeinated tea use was more common among controls than among AF cases (P=0.03).
There was no association between any consumption of caffeinated or decaffeinated soda and AF. Although consuming ≥ 1 can of caffeinated soda daily was significantly associated with a decreased risk for hepatic fibrosis (P=0.015), this association was reduced after adjusting for age, BMI, and alcohol use, and for MELD score and the presence of metabolic syndrome (P=0.047). And it was further attenuated when adjusted for diabetes and HOMA-IR scores (P=0.063). In addition, among the subset of non-coffee drinkers, intake of ≥ 1 can of caffeinated soda was not significant.
Overall, average daily caffeine consumption from all beverages was higher in the controls (273.8 mg) than in the AF cases (218.2 mg) (P=0.013), as was the average daily intake of caffeine from coffee (P=0.028). Caffeine was consumed mostly from coffee, followed by soda and then tea. Stratified by dose, participants consuming ≥ 100 mg caffeine daily from any source had a significantly reduced risk of AF (P=0.014), as did those consuming ≥ 100 mg caffeine daily from coffee (P=0.035); however, the association was not significant among non-coffee drinkers consuming ≥ 100 mg caffeine daily. The average daily intake of coffee in prior life decades was not significant.
There were no significant associations between AF and the use of creamers/whiteners (37% of the participants) or sweeteners (23.8% of the participants).
Among the 650 nondiabetic participants, those with a HOMA-IR value ˂ 3 (in the normal range) were significantly more likely to consume more than 100 mg of caffeine daily than were the participants with HOMA-IR values of ≥ 3 (P=0.012). This association between caffeine intake and decreased risk of insulin resistance was significant after adjusting for age, BMI, and alcohol use (P=0.022); MELD score (P=0.024); and the presence of metabolic syndrome (P=0.017).
An average daily intake of 100 mg or more of caffeine from all sources was associated with a significantly decreased risk for AF (P=0.02) after adjusting for age, alcohol use, and BMI, and after adjusting for MELD scores in a second multivariate model. In a third model, adjusting for insulin resistance minimally reduced the association; however, the association between caffeine intake and decreased risk for AF remained significant after adjusting for the presence of metabolic syndrome (P=0.014).
In this study, an average daily intake of ≥ 100 mg of caffeine was associated with a lower risk for advanced hepatic fibrosis in patients with chronic HCV infection. In non-coffee drinkers, daily caffeinated tea intake (but not caffeinated soda) was also associated with decreased risk of progressive liver disease. Overall, consuming caffeinated coffee or caffeinated tea is more beneficial for patients with HCV than consuming other caffeinated beverages or decaffeinated coffee.
"If validated in other HCV-infected populations in the United States, our results suggest that a relatively low (and therefore potentially more tolerable dose) of caffeine, particularly from caffeinated coffee and possibly from tea, may convey a substantial reduction in fibrosis progression." The authors conclude that "prospective studies are warranted to determine the optimal dose and preparation of caffeinated beverage intake that could be safely and tolerably recommended for prevention of progressive liver disease in HCV patients in routine clinical practice."
--Shari Henson
Source : American Botanical Council
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Protective effects of extracts from Pomegranate peels and seeds on liver fibrosis induced by carbon tetrachloride in rats
Xiang-lan Wei12, Ru-tang Fang3, Yong-hua Yang4, Xue-yuan Bi1, Guo-xia Ren2, A-li Luo2,Ming Zhao1* and Wei-jin Zang1*
Abstract
Liver fibrosis is a feature in the majority of chronic liver diseases and oxidative stress is considered to be its main pathogenic mechanism. Antioxidants including vitamin E, are effective in preventing liver fibrogenesis. Several plant-drived antioxidants, such as silymarin, baicalin, beicalein, quercetin, apigenin, were shown to interfere with liver fibrogenesis. The antioxidans above are polyphenols, flavonoids or structurally related compounds which are the main chemical components of Pomegranate peels and seeds, and the antioxidant activity of Pomegranate peels and seeds have been verified. Here we investigated whether the extracts of pomegranate peels (EPP) and seeds (EPS) have preventive efficacy on liver fibrosis induced by carbon tetrachloride (CCl 4 ) in rats and explored its possible mechanisms.
Source : BMC Complementary and Alternative Medicine
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Buckwheat Honey Attenuates Carbon Tetrachloride-Induced Liver and DNA Damage in Mice
Ni Cheng,1,2 Liming Wu,3 Jianbin Zheng,2 and Wei Cao1,2
Abstract
Buckwheat honey, which is widely consumed in China, has a characteristic dark color. The objective of this study was to investigate the protective effects of buckwheat honey on liver and DNA damage induced by carbon tetrachloride in mice. The results revealed that buckwheat honey had high total phenolic content, and rutin, hesperetin, and p-coumaric acid were the main phenolic compounds present. Buckwheat honey possesses super DPPH radical scavenging activity and strong ferric reducing antioxidant power. Administration of buckwheat honey for 10 weeks significantly inhibited serum lipoprotein oxidation and increased serum oxygen radical absorbance capacity. Moreover, buckwheat honey significantly inhibited aspartate aminotransferase and alanine aminotransferase activities, which are enhanced by carbon tetrachloride. Hepatic malondialdehyde decreased and hepatic antioxidant enzymes (superoxide dismutase and glutathione peroxidase) increased in the presence of buckwheat honey. In a comet assay, lymphocyte DNA damage induced by carbon tetrachloride was significantly inhibited by buckwheat honey. Therefore, buckwheat honey has a hepatoprotective effect and inhibits DNA damage, activities that are primarily attributable to its high antioxidant capacity.
Source : Evidence Based Complementary and Alternative Medcine Journal
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Yiguanjian decoction and its ingredients inhibit angiogenesis in carbon tetrachloride-induced cirrhosis mice
Ya-Ning Zhou1†, Yong-Ping Mu1†, Wen-Wei Fu1, Bing-Bing Ning1, Guang-Li Du2, Jia-Mei Chen1, Ming-Yu Sun1, Hua Zhang1, Yi-Yang Hu13, Cheng-Hai Liu13, Lie-Ming Xu1 and Ping Liu13*
Abstract
Cirrhosis is associated with angiogenesis and disruption of hepatic vascular architecture. Yiguanjian (YGJ) decoction, a prescription from traditional Chinese medicine, is widely used for treating liver diseases. We studied whether YGJ or its ingredients (iYGJ) had an anti-angiogenic effect and explored possible mechanisms underlying this process.
MethodsCirrhosis was induced with carbon tetrachloride (CCl 4 ) (ip) in C57BL/6 mice for 6 weeks. From week 4 to week 6, cirrhotic mice were randomly divided into four groups: sorafenib-treated, YGJ-treated and iYGJ-treated mice and placebo. Serum biochemistries, hydroxyproline (Hyp) content and histopathological changes of hepatic tissues were measured as were α-smooth muscle actin (α-SMA), collagen I, CD31, vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR) 2 and hypoxia-inducible factor (HIF)-1α.
ResultsBoth YGJ and iYGJ improved serum biochemistries. Changes of histopathology showed that YGJ and iYGJ reduced hepatic tissue necroinflammatory and collagen fiber deposition in cirrhosis mice. Compared to the CCl 4 treated animals, Hyp, α-SMA, collagen I, CD31, VEGF, VEGFR, and HIF-1α expression decreased in YGJ and iYGJ groups.
ConclusionsYGJ and iYGJ inhibited liver angiogenesis in cirrhotic mice treated with CCl 4 by inhibiting the HIF-1α/VEGF signaling pathway, suggesting that anti-angiogenic effects of YGJ and iYGJ are associated with improving the hepatic hypoxic microenvironment.
Source : BMC Complementary and Alternative Medicine
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A double-blinded randomized controlled trial of silymarin for the prevention of antituberculosis drug-induced liver injury
Chote Luangchosiri1, Ammarin Thakkinstian2, Sermsiri Chitphuk3, Wasana Stitchantrakul3, Supanna Petraksa1 and Abhasnee Sobhonslidsuk14*
Abstract
Background Hepatitis is a common adverse effect of antituberculosis drugs. Silymarin prevented drug-induced hepatoxicity in animals with anti-oxidative mechanisms but its effect in human has been unknown. We aimed to evaluate the efficacy of silymarin for preventing antituberculosis-drug induced liver injury (antiTB-DILI) in patients with tuberculosis.
Methods A double-blind randomized placebo-controlled trial was performed. Tuberculosis patients were randomly allocated to receive placebo or silymarin. The outcomes of interests were antiTB-DILI and the maximum liver enzymes at week 4. Antioxidative enzymes (i.e., superoxide dismutase (SOD), glutathione and malondialdehyde assays) were assessed. The risks of antiTB-DILI between the two groups were compared. A number need to treat was estimated.
Results A total of 55 out of 70 expected numbers of patients were enrolled. There were 1/27 (3.7 %) and 9/28 (32.1 %) patients who developed antiTB-DILI in the silymarin and the placebo groups. Risk reduction was 0.28 (0.10, 0.47), i.e., receiving silymarin was 28 % at lower risk for antiTB-DILI than placebo. This led to prevention of 28 patients from being antiTB-DILI among 100 treated patients. Median (IQR) of ALT levels at week 4 in the placebo and the silymarin group were 35.0 (15, 415) IU/L and 31.5 (20, 184) IU/L (p = 0.455). The decline of SOD level at week 4 in the silymarin group was less than the placebo group (p < 0.027).
Conclusions Silymarin reduced the incidence of antiTB-DILI. The benefit of silymarin may be explained from superoxide dismutase restoration. Larger clinical trials are required to confirm the result of our small study
Source : BMC Complementary and Alternative Medicine
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Hepatoprotective effect of mulberry (Morus nigra) leaves extract against methotrexate induced hepatotoxicity in male albino rat
Hend M. Tag
Abstract
Drug-induced liver injury is a major health problem that challenges not only health care professionals but also the pharmaceutical industry and drug regulatory agencies. The possible hepatoprotective effect of the administration of mulberry ethanolic extract (MUL) leaves against hepatotoxic effect of the anti-rheumatic drug, methotrexate (MTX) was evaluated in this study both vivo (using animal models) and in vitro (human hepatoma HepG2 cells).
Methods
In the in-vivo study, 20 male albino rats were equally assigned into four groups; control group received distilled water orally; MUL treated-group received 500 mg/kg/day of MUL extract; MTX treated-group was injected with a single dose of 20 mg/kg MTX intraperitoneally on the 4th day; MUL-MTX treated-group received the previously mentioned doses of MUL and MTX (both control and MUL treated groups were administered a single dose of a physiological saline i.p.). At the end of the experimental period (14 days) activities of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) as well as total serum protein (TP) and albumin (ALB) levels were evaluated to assess liver function.
Results
A marked reduction in the viability of HepG2 cells was observed after 48 h with IC 50 equal to 14.5 μg/mL of MUL administration. Treating the animals with MUL in combination with MTX mitigated liver injury, causing a significant reduction in activities of AST, ALT, ALP and LDH as compared to the MTX-group. The liver architecture revealed more or less normal appearance with the combined treatment when compared with MTX treatment alone.
Conclusions
This study recommends that the co-administration of MUL with MTX that may have therapeutic benefits against MTX-hepato-cytotoxicity.
Source BMC Complementary and Alternative Medicine
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Genistein Attenuates Nonalcoholic Steatohepatitis and Increases Hepatic PPARγ in a Rat Mode
lWarinda Susutlertpanya,1 Duangporn Werawatganon,1 Prasong Siriviriyakul,1 and Naruemon Klaikeaw2
1Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
2Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
Abstract
Nonalcoholic steatohepatitis (NASH) has become a global chronic liver disease, but no effective medicine has been proven to cure it. This study investigated the protective effects of genistein, a phytoestrogen, on NASH and examined whether it has any effect on hepatic PPARγ. Male Sprague-Dawley rats were divided into four groups: control group fed ad libitum with standard rat diet, NASH group fed ad libitum with high-fat diet to induce NASH and NASH + Gen8 group and NASH + Gen16 group fed with high-fat diet plus intragastric administration of 8 or 16 mg/kg genistein once daily. After 6 weeks, liver samples were collected to determine MDA, TNF-α, PPARγ, and histopathology. The findings were that levels of hepatic MDA and TNF-αincreased in NASH group, but 16 mg/kg genistein reduced these levels significantly. Downregulation of hepatic PPARγ was observed in NASH group, but genistein significantly upregulated the expression of PPARγin both NASH + Gen groups. The histological appearance of liver in NASH group presented pathological features of steatohepatitis which were diminished in both NASH + Gen groups. The results suggest that genistein attenuates the liver histopathology of NASH with upregulation of hepatic PPARγ, reduction of oxidative stress, and inhibition of inflammatory cytokine.
Source : Evidence Based Complementary and Alternative Medicine
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Antioxidant effects of pineapple vinegar in reversing of paracetamol-induced liver damage in mice
Nurul Elyani Mohamad1, Swee Keong Yeap2, Kian Lam Lim3, Hamidah Mohd Yusof1, Boon Kee Beh3, Sheau Wei Tan2, Wan Yong Ho4, Shaiful Adzni Sharifuddin5, Anisah Jamaluddin5, Kamariah Long5, Nik Mohd Afizan Nik Abd Rahman1 and Noorjahan Banu Alitheen1*
Abstract
Background
Pineapple (Ananas comosus) was demonstrated to be hepatoprotective. This study aims to investigate the reversing effects of pineapple vinegar on paracetamol-induced liver damage in murine model.
Methods
Pineapple juice was fermented via anaerobic and aerobic fermentation to produce pineapple vinegar. Male BALB/c mice (n = 70) were separated into 7 treatment groups (n = 10). Pineapple vinegar (0.08 and 2 mL/kg BW) and synthetic vinegar were used to treat paracetamol-induced liver damage in mice. The hepatoprotective effects were determined by serum biochemistry profiles (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and triglyceride (TG)), liver antioxidant levels (ferric-reducing ability plasma (FRAP), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), and reduced glutathione assays (GSH)) and histopathological examination with hematoxylin and eosin (H&E) staining. The effects were further evaluated by the expression levels of iNOS, NF-κB, and cytochrome P450 2E1 by quantitative real-time PCR and Western blot analyses. Vinegar samples were also tested for in vitro antioxidant (FRAP, 2,2-diphenyl-2-picrylhydrazyl (DPPH), and total phenolic content (TPC)). Soluble phenolic acid contents in the samples were identified by HPLC.
Results
Pineapple vinegar contained 169.67 ± 0.05 μg GAE/mL of TPC, with 862.61 ± 4.38 μg/mL gallic acid as the main component. Oral administration of pineapple vinegar at 2 mL/kg BW reduced serum enzyme biomarker levels, including AST (P = 0.008), ALT (P = 0.006), ALP (P= 0.002), and TG (P = 0.006) after 7 days of paracetamol treatment. Liver antioxidant levels such as hepatic glutathione (P = 0.003), SOD (P < 0.001), lipid peroxidation (P = 0.002) and FRAP (P <0.001) were restored after the treatment. Pineapple vinegar reduced the expressions of iNOS (P = 0.003) and NF-kB (P = 0.003) and the level of NO (P = 0.003) significantly. Pineapple vinegar also downregulated liver cytochrome P450 protein expression.
Conclusions
Oral administration of pineapple vinegar at 0.08 and 2 mL/kg BW reduced serum enzyme biomarker levels, restored liver antioxidant levels, reduced inflammatory factor expressions, and down regulated liver cytochrome P450 protein expression in paracetamol-induced liver damage in mice.
Source : Journal Chinese Medicine
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Anti-fatty liver effects of oils from Zingiber officinale and Curcuma longa on ethanol-induced fatty liver in rats
1. Sarah Onyenibe Nwozo (Nutritional and Industrial Research Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan 200002, Nigeria E-mail: [email protected])
2. Damilola Adeola Osunmadewa (Nutritional and Industrial Research Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan 200002, Nigeria )
3. Babatunji Emmanuel Oyinloye (Nutritional and Industrial Research Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan 200002, Nigeria )
ABSTRACT
OBJECTIVE: The present study is aimed at evaluating the protective effects of oils from Zingiber officinale (ginger) and Curcuma longa (turmeric) on acute ethanol-induced fatty liver in male Wistar rats.
METHODS: Ferric reducing antioxidant power activity and oxygen radical absorbance capacity of the oils were evaluated ex vivo. Rats were pretreated for 28 d with standard drug (Livolin Forte) and oils from Z. officinale and C. longa before they were exposed to 45% ethanol (4.8 g/kg) to induce acute fatty liver. Histological changes were observed and the degree of protection was measured by using biochemical parameters such as alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities. Serum triglyceride (TG) level, total cholesterol (TC) level and the effects of both oils on reduced gluthatione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD) and hepatic malondialdehyde (MDA) levels were estimated.
RESULTS: Oils from Z. officinale and C. longa at a dose of 200 mg/kg showed hepatoprotection by decreasing the activities of serum enzymes, serum TG, serum TC and hepatic MDA, while they significantly restored the level of GSH as well as GST and SOD activities. Histological examination of rats tissues was related to the obtained results.
CONCLUSION: From the results it may be concluded that oils from Z. officinale and C. longa (200 mg/kg) exhibited hepatoprotective activity in acute ethanol-induced fatty liver and Z. officinale oil was identified to have better effects than C. longa oil.
Source : Journal Chinese Integrative Medicine
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Hepatoprotective effect of cryptotanshinone from Salvia miltiorrhiza in D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure.
Introduction
Fulminant hepatic failure (FHF) is a life-threatening clinical syndrome and characterized by coagulopathy, jaundice and multisystem organ failure and a very high mortality, even though there is still no available therapy except liver transplantation limited by the chronic shortage of donor livers (Van Thiel et al. 2002).
D-Galactosamine (GalN) and lipopolysaccharide (LPS)-induced hepatitis in mice is a commonly used test model with endotoxemic shock and fulminant hepatic failure, which is similar to fulminant hepatic failure in clinic (Hishinuma et al. 1990). In the GalN/LPS model, LPS, as the bacterial cell wall component is used to initiate the inflammatory response. Because rodents are less sensitive to LPS exposure than humans, LPS is combined with the amino sugar GalN to sensitize the animals. In response to the infection in mammals LPS is detected by immune cells such as monocytes, macrophages and hepatic Kupffer cells (Liaskou et al. 2012). The combined exposure to GalN/LPS activates Kupffer cells to produce tumor necrosis factor (TNF)-[ALPHA], consequently results in hepatocyte apoptosis, in the early stages of the LPS-induced liver injury in GalN-sensitized mice (Jaeschke et al. 1998). Then in the later stages of liver injury neutrophils transmigrate and attack hepatocytes, and eventually cause massive hepatocyte necrosis and multiorgan failure (Ramaiah and Jaeschke 2007).
Mitogen-activated protein kinases (MAPKs) family including p38 kinase, c-Jun N-terminal kinase (JNK) and extracellular signal regulated kinase (ERK) serve to regulate diverse cellular responses to extracellular stimuli, and modulate various cellular activities including gene expression, mitosis, differentiation and cell survival/apoptosis. With regard to the regulation of MAPKs, it is well known that nuclear factor (NF)-[kappa]B is an important transcriptional factor involved in the expression of TNF-[alpha] and interleukin (IL)-1 (Aggarwal 2004). In unstimulated cells, NF-[KAPPA]B is sequestered in an inactive form in the cytoplasm bound to inhibitory I[kappa]B protein. Stimulation leads to the rapid phosphorylation, ubiquitination, and degradation of I[KAPPA]B, which frees NF-[kappa]B to translocate to the nucleus and activate the transcription of proinflammatory genes (Karin and Ben-Neriah 2000). Therefore, an insight into the regulation of signaling pathways by MAPKs and NF-[kappa]B is indispensable for developing a treatment based on their inhibition.
Despite an increasing need for agents to protect the liver from damage, much less modern medicine is reliable regarding how to protect liver from diverse risks. Therefore, intense attention has been devoted to natural sources for the prevention and treatment of various liver diseases. Components from natural products used in folk herbs are expected to be therapeutically effective and have much lower toxicity when clinically used. Recently, we screened a numbers of natural substances, which are used traditionally for liver diseases (Lian et al. 2010b; Nan et al. 2004; Wan et al. 2010). Especially, we have reported that, in murine macrophage 264.7, cryptotanshinone (CTN) effectively inhibited LPS-triggered TLR4 signaling and NF-[kappa]B downstream pathways (Li et al. 2011). Cryptotanshinone is a major active Iipid-soluble constituent of Salvia miltiorrhiza Bunge (reputed "Danshen") (Zhong et al. 2009), which is commonly used in the Traditional Chinese Medicine system. It was reported that Salvia m. ameliorates cirrhosis and portal hypertension, and also protects against doxorubicin-induced hepatic toxicity (Wagner and Ulrich-Merzenich 2013 and references therein). Cryptotanshinone possesses anti-cancer, antiinflammatory and anti-oxidative activities (Lee et al. 2009; Li et al. 2011; Tang et al. 2011). In previous research, we also found that CTN significantly increased the survival rate against LPS challenge in GalN-sensitized mice. Additionally Park et al. (2009) have reported that cryptotanshinone-containing purified extract of Salvia m. protects hepatocytes from GalN-induced liver toxicity in vitro. Those together with previous in vitro results (Li et al. 2011) intrigued us to further investigate whether cryptotanshinone could attenuate GalN/LPS-induced fulminant liver failure in mice.
Source : International Journal of Phytotherapy and Phytopharmacology
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Ginsenosides Rg1 from Panax ginseng: A Potential Therapy for Acute Liver Failure Patients?
Jinqiu Zhao, Zhengyu Shi, Shu Liu, Jiajun Li, and Wenxiang Huang
Department of Infectious Diseases, The First Affiliated Hospital, Chongqing Medical University, Yuzhong District, Chongqing 400016, China
Abstract
Acute liver failure (ALF) is a rapidly progressing critical illness with a high mortality rate. Circulating inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), play a significant role in the pathophysiology of ALF through promoting hepatocellular apoptosis. Ginsenoside Rg1, the primary active ingredient in Panax ginseng (also termed Asian or Korean ginseng), has been reported to inhibit TNF-αproduction and has been shown to significantly attenuate liver fibrosis development. Here, we assessed ginsenoside Rg1’s potential as a therapy for ALF by investigating the effect of ginsenoside Rg1 treatment on circulating inflammatory markers, hepatocellular apoptosis, and relevant apoptotic signaling pathways in a well-established murine ALF model. We found that ginsenoside Rg1 significantly reduces liver damage in a murine ALF model through inhibiting TNF-α-induced, caspase-dependent hepatocellular apoptosis. These results support the further investigation of ginsenoside Rg1 as a therapeutic candidate for ALF.
Source : Journal Evidence Based Complementary and Alternative Medicine
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Hepatoprotective Effects of Silybum marianum (Silymarin) and Glycyrrhiza glabra (Glycyrrhizin) in Combination: A Possible Synergy
Mahmood Rasool,1 Javed Iqbal,2 Arif Malik,3 Hafiza Sobia Ramzan,3 Muhammad Saeed Qureshi,3 Muhammad Asif,4 Mahmood Husain Qazi,5 Mohammad Amjad Kamal,6 Adeel Gulzar Ahmed Chaudhary,1 Mohammed Hussain Al-Qahtani,1 Siew Hua Gan,7 and Sajjad Karim1
1Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Post Box No. 80216, Jeddah 21589, Saudi Arabia
2Department of Pharmacy, University of Lahore, Pakistan
3The Institute of Molecular Biology and Biotechnology, University of Lahore, Pakistan
4Department of Biotechnology and Informatics, BUITEMS, Quetta, Pakistan
5Center for Research in Molecular Medicine, University of Lahore, Pakistan
6King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
7Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia
Abstract
Oxidative stress, lipid peroxidation, and transaminase reactions are some of the mechanisms that can lead to liver dysfunction. A time-dependent study was designed to evaluate the ability of silymarin (SLN) and glycyrrhizin (GLN) in different dosage regimens to lessen oxidative stress in the rats with hepatic injury caused by the hepatotoxin carbon tetrachloride. Wistar male albino rats ( = 60) were randomly assigned to six groups. Group A served as a positive control while groups B, C, D, E, and F received a dose of CCl4 (50% solution of CCl4 in liquid paraffin, 2 mL/kg, intraperitoneally) twice a week to induce hepatic injury. Additionally, the animals received SLN and GLN in different doses for a period of six weeks. CCl4 was found to induce hepatic injury by significantly increasing serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and thiobarbituric acid reactive substances while decreasing total protein and the activities of reduced glutathione, superoxide dismutase, and catalase. Treatment with various doses of SLN and GLN significantly reduced ALT, AST, ALP, and TBARS levels and increased GSH, SOD, and CAT levels. Our findings indicated that SLN and GLN have hepatoprotective effects against oxidative stress of the liver.
Source : Evidence Based Complementary and Alternative Medicine
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Current evidence for the hepatoprotective activities of the medicinal mushroom Antrodia cinnamomea
Patrick Ying-Kit Yue1*, Yi-Yi Wong1, Kay Yuen-Ki Wong1, Yeuk-Ki Tsoi2 and Kelvin Sze-Yin Leung2*
1 Department of Biology, Faculty of Science, Hong Kong Baptist University, Hong Kong, SAR, China
2 Department of Chemistry, Faculty of Science, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China
Abstract
Antrodia cinnamomea (AC) is an endemic mushroom species of Taiwan, and has been demonstrated to possess diverse biological and pharmacological activities, such as anti-hypertension, anti-hyperlipidemia, anti-inflammation, anti-oxidation, anti-tumor, and immunomodulation. This review focuses on the inhibitory effects of AC on hepatitis, hepatocarcinoma, and alcohol-induced liver diseases (e.g., fatty liver, fibrosis). The relevant biochemical and molecular mechanisms are addressed. Overall, this review summarizes the hepatoprotective activities in vitro and in vivo. However, there is no doubt that human and clinical trials are still limited, and further studies are required for the development of AC-related products.
Source : Journal Chinese Medicine
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Coffee and Tea May Contribute to a Healthy Liver
Your morning cup of tea or coffee may be doing more than just perking you up before work.
An international team of researchers led by Duke-NUS Graduate Medical School (Duke-NUS) and the Duke University School of Medicine suggest that increased caffeine intake may reduce fatty liver in people with non-alcoholic fatty liver disease (NAFLD).
Worldwide, 70 percent of people diagnosed with diabetes and obesity have NAFLD, the major cause of fatty liver not due to excessive alcohol consumption. It is estimated that 30 percent of adults in the United States have this condition, and its prevalence is rising in Singapore. There are no effective treatments for NAFLD except diet and exercise.
Using cell culture and mouse models, the study authors -- led by Paul Yen, M.D., associate professor and research fellow, and Rohit Sinha, Ph.D of the Duke-NUS Graduate Medical School's Cardiovascular and Metabolic Disorders Program in Singapore -- observed that caffeine stimulates the metabolization of lipids stored in liver cells and decreased the fatty liver of mice that were fed a high-fat diet. These findings suggest that consuming the equivalent caffeine intake of four cups of coffee or tea a day may be beneficial in preventing and protecting against the progression of NAFLD in humans.
The findings will be published in the September issue of the journal Hepatology.
"This is the first detailed study of the mechanism for caffeine action on lipids in liver and the results are very interesting," Yen said. "Coffee and tea are so commonly consumed and the notion that they may be therapeutic, especially since they have a reputation for being "bad" for health, is especially enlightening."
The team said this research could lead to the development of caffeine-like drugs that do not have the usual side effects related to caffeine, but retain its therapeutic effects on the liver. It could serve as a starting point for studies on the full benefits of caffeine and related therapeutics in humans.
Source : Newswise
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Antioxidant Properties of Taraxacum officinale Leaf Extract Are Involved in the Protective Effect Against Hepatoxicity Induced by Acetaminophen in Mice
Dirleise Colle,1Leticia Priscilla Arantes,1Priscila Gubert,1Sonia Cristina Almeida da Luz,2 Margareth Linde Athayde ,3Joa ̃o Batista Teixeira Rocha,1and Felix Alexandre Antunes Soares1
1Department of Chemistry, Natural and Exact Sciences Center; Departments of 2Pathology and 3Industrial Pharmacy ,Health Sciences Center; Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, Brazil
.ABSTRACT
Acetaminophen (APAP) hepatotoxicity has been related to several cases of hepatitis, cirrhosis, and hepatic transplant. As APAP hepatotoxicity is related to reactive oxygen species (ROS) formation and excessive oxidative stress, natural antioxidant compounds have been tested as an alternative therapy to diminish the hepatic dysfunction induced by APAP. Taraxacum officinale Weber (Family Asteraceae), commonly known as dandelion, is used for medicinal purposes because of its choleretic, diuretic, antioxidant, anti-inflammatory, and hepatoprotective properties. This study evaluated the hepatoprotective activity of T. officinale leaf extract against APAP-induced hepatotoxicity.T. officinale was able to decrease thiobarbituric acid–reactive substance levels induced by 200 mg/kg APAP (p.o.), as well as prevent the decrease in sulfhydryl levels caused by APAP treatment. Furthermore, histopathological alterations, as well as the increased levels of serum aspartate and alanine aminotransferases caused by APAP, were prevented by T. officinale(0.1 and 0.5 mg/mL). In addition, T. officinale extract also demonstrated antioxidant activity in vitro, as well as scavenger activity against 2,2-diphenyl-1-picrylhydrazyl and nitric oxide radicals. Our results clearly demonstrate the hepatoprotective effect of T. officinale against the toxicity induced by APAP. The possible mechanisms involved include its scavenger activities against ROS and reactive nitrogen species, which are attributed to the content of phenolic compounds in the extract.
Source : Journal of Medicinal Food
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Hepatoprotective effect of water extract from Chrysanthemum indicum L. flower
Sang Chul Jeong, Sang Min Kim, Yong Tae Jeong and Chi Hyun Song
Abstract
Chrysanthemum indicum L. flower (CIF) has been widely used as tea in Korea. This study aims to investigate the hepatoprotective effect of the hot water extract of CIF (HCIF) in in vitro and in vivo systems.
Methods Hepatoprotective activities were evaluated at 250 to 1000 mug/ml concentrations by an in vitro assay using normal human hepatocytes (Chang cell) and hepatocellular carcinoma cells (HepG2) against CCl4-induced cytotoxicity. Cytochrome P450 2E1, which is a key indicator of hepatic injury, was detected by western blot analysis using rabbit polyclonal anti-human CYP2E1 antibody. An in vivo hepatoprotective activity assay was performed at 1000 to 4000 mug/ml concentrations on CCl4-induced acute toxicity in rats, and the serum levels of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were determined by standard enzyme assays.
Results The hepatoprotective effects of HCIF significantly reduced the levels of GOT (60.1%, P = 0.000) and GPT (64.5%, P = 0.000) compared with the vehicle control group (CCl4 alone). The survival rates of HepG2 and Chang cells were significantly improved compared with the control group [82.1% (P = 0.034) and 62.3% (P = 0.002), respectively]. HCIF [50 mg/kg body weight (BW)] treatment significantly reduced the serum levels of GOT (49.5%, P = 0.00), GPT (55.5%, P = 0.00), ALP (30.8%, P = 0.000) and LDH (45.6%, P = 0.000) compared with the control group in this in vivo study. The expression level of cytochrome P450 2E1 (CYP2E1) protein was also significantly decreased at the same concentration (50 mg/kg BW; P = 0.018).
Conclusion HCIF inhibited bioactivation of CCl4-induced hepatotoxicity and downregulates CYP2E1 expression in vitro and in vivo.
Source : Chinese Medicine
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Haematological and Hepatotoxic Potential of Onion (Allium cepa) and Garlic (Allium sativum) Extracts in Rats
Enitan Seyi Samson1*, Ajeigbe Kazeem Olasunkanmi1, Josiah Sunday Joel2 and Ehiaghe Friday Alfred3
1Department of Physiology, School of Basic Medical Sciences, College of Health Sciences, Igbinedion University Okada, P.M.B. 0006, Edo state, Nigeria.
2Department of Biochemistry, School of Basic Medical Sciences, College of Health
Sciences, Igbinedion University Okada, P.M.B. 0006, Edo state, Nigeria.
3Department of Haematology, School of Clinical Medicine, College of Health Sciences, Igbinedion University Okada, P.M.B. 0006, Edo state, Nigeria.
Abstract
Aims: To evaluate and compare the effects of single and combined oral administration of fresh aqueous onion (Allium cepa) and garlic (Allium sativum) extracts at different concentrations (200mg/kg/d, 400mg/kg/d and 600mg/kg/d) on some haematological and
hepatotoxicity indicator parameters in treated rats.
Study Design: Cross-sectional nonclinical study in animal model.
Place and Duration of Study: The study was carried out at the Department of Physiology, Department of Biochemistry and Department of Haematology, College of Health Sciences, Igbinedion University Okada, Edo state, Nigeria between the month of
July and August, 2011.
Methodology: Following 30 days post-oral administration of extracts in 36 treated male albino rats as well as 4 controls, haematological parameters were determined using the Sysmex® Automated Haematology Analyzer, while serum levels of liver enzymes were evaluated using the Reflotron® Plus Auto-Analyzer and liver weight was determined using electronic sensitive weighing balance.
Results: Red blood cell count (RBC), Packed cell volume (PCV), Haemoglobin concentration (HGB), Total White blood cell count (TWBC), Absolute Count of Neutrophil (NEUT#), Absolute Count of Lymphocyte (LYM#), Absolute Count of the summation of
Monocyte, Eosinophil and Basophil (MXD#) and Platelet count (PLT) were significantly increased (P<0.05) to varied extent, except Mean cell volume (MCV), Mean cell haemoglobin (MCH) and Mean cell haemoglobin concentration (MCHC) while Alanine
aminotransferase (ALAT) and Aspartate aminotransferase (ASAT) serum levels were significantly decreased (P<0.001) and liver weight (LW) was non-significantly (P>0.05) reduced in a dose-dependent manner when compared to the control. Synergistic effect
was not observed in the haematological parameters when the two extracts were combined.
Conclusion: The results of this study reveal the haematological potential of onion and garlic extracts with no potential risk of hepatotoxicity (at the concentrations tested) as earlier anticipated. It also further confirms the higher efficacy of garlic over
that of onion, but the molecular mechanism behind their combined effect would require further investigation.
Source European Journal of Medicinal Plants, 2(4): 290-307, 2012
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Long-Term Zinc Supplementation Improves Liver Function and Decreases the Risk of Developing Hepatocellular Carcinoma
Atsushi Hosui *, Eiji Kimura, Sumiko Abe, Takashi Tanimoto, Kousaku Onishi, Yukihiro Kusumoto, Yuka Sueyoshi, Kengo Matsumoto, Motohiro Hirao, Takuya Yamada and Naoki Hiramatsu
Abstract
Zinc plays a pivotal role in various zinc enzymes, which are crucial in the maintenance of liver function. Patients with chronic liver diseases (CLDs) usually have lower concentrations of zinc, which decrease further as liver fibrosis progresses. Whether long-term zinc supplementation improves liver function and reduces the risk of hepatocellular carcinoma (HCC) development remains unknown. Two hundred and sixty-seven patients with CLDs who received a zinc preparation (Zn-group; 196 patients), or who did not receive zinc (no Zn-treatment group; 71 patients), were retrospectively analyzed in this study. The Zn-group was divided into 4 groups according to their serum Zn concentrations at 6 months after the start of Zn treatment. Liver function significantly deteriorated in the no Zn-treatment group, while no notable change was observed in the Zn-group. The cumulative incidence rates of events and HCC at 3 years were observed to be lower in the Zn-group (9.5%, 7.6%) than in the no Zn-treatment group (24.9%, 19.2%) (p < 0.001). According to serum Zn concentrations, the cumulative incidence rates of events and HCC were significantly decreased in patients with Zn concentrations ≥ 70 µg/dL (p < 0.001). Zinc supplementation appears to be effective at maintaining liver function and suppressing events and HCC development, especially among patients whose Zn concentration is greater than
70 µg/dL.
Source : Journal Nutrients
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A network pharmacology-based study on the anti-hepatoma effect of Radix Salviae Miltiorrhizae
Yi Luo, Yu Feng, Lei Song, Gan-Qing He, Sha Li, Sha-Sha Bai, Yu-Jie Huang, Si-Ying Li, Mohammed M. Almutairi, Hong-Lian Shi, Qi Wang & Ming Hong
Abstract
Background
Radix Salviae Miltiorrhizae (RSM), a well-known traditional Chinese medicine, has been shown to inhibit tumorigenesis in various human cancers. However, the anticancer effects of RSM on human hepatocellular carcinoma (HCC) and the underlying mechanisms of action remain to be fully elucidated.
Methods
In this study, we aimed to elucidate the underlying molecular mechanisms of RSM in the treatment of HCC using a network pharmacology approach. In vivo and in vitro experiments were also performed to validate the therapeutic effects of RSM on HCC.
Results
In total, 62 active compounds from RSM and 72 HCC-related targets were identified through network pharmacological analysis. RSM was found to play a critical role in HCC via multiple targets and pathways, especially the EGFR and PI3K/AKT signaling pathways. In addition, RSM was found to suppress HCC cell proliferation, and impair cancer cell migration and invasion in vitro. Flow cytometry analysis revealed that RSM induced cell cycle G2/M arrest and apoptosis, and western blot analysis showed that RSM up-regulated the expression of BAX and down-regulated the expression of Bcl-2 in MHCC97-H and HepG2 cells. Furthermore, RSM administration down-regulated the expression of EGFR, PI3K, and p-AKT proteins, whereas the total AKT level was not altered. Finally, the results of our in vivo experiments confirmed the therapeutic effects of RSM on HCC in nude mice.
Conclusions
We provide an integrative network pharmacology approach, in combination with in vitro and in vivo experiments, to illustrate the underlying therapeutic mechanisms of RSM action on HCC.
Source : Journal Chinese Medicine
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Coffee prevents fatty liver disease induced by a high-fat diet by modulating pathways of the gut–liver axis
Paola Vitaglione (a1) (a2), Giovanna Mazzone (a3), Vincenzo Lembo (a3), Giuseppe D'Argenio (a3)
Abstract
Coffee consumption is inversely associated with the risk of non-alcoholic fatty liver disease (NAFLD). A gap in the literature still exists concerning the intestinal mechanisms that are involved in the protective effect of coffee consumption towards NAFLD. In this study, twenty-four C57BL/6J mice were divided into three groups each receiving a standard diet, a high-fat diet (HFD) or an HFD plus decaffeinated coffee (HFD+COFFEE) for 12 weeks. Coffee supplementation reduced HFD-induced liver macrovesicular steatosis (P < 0·01) and serum cholesterol (P < 0·001), alanine aminotransferase and glucose (P < 0·05). Accordingly, liver PPAR- α(P < 0·05) and acyl-CoA oxidase-1 (P < 0·05) as well as duodenal ATP-binding cassette (ABC) subfamily A1 (ABCA1) and subfamily G1 (ABCG1) (P < 0·05) mRNA expressions increased with coffee consumption. Compared with HFD animals, HFD+COFFEE mice had more undigested lipids in the caecal content and higher free fatty acid receptor-1 mRNA expression in the duodenum and colon. Furthermore, they showed an up-regulation of duodenal and colonic zonulin-1 (P < 0·05), duodenal claudin (P < 0·05) and duodenal peptide YY (P < 0·05) mRNA as well as a higher abundance of Alcaligenaceae in the faeces (P < 0·05). HFD+COFFEE mice had an energy intake comparable with HFD-fed mice but starting from the eighth intervention week they gained significantly less weight over time. Data altogether showed that coffee supplementation prevented HFD-induced NAFLD in mice by reducing hepatic fat deposition and metabolic derangement through modification of pathways underpinning liver fat oxidation, intestinal cholesterol efflux, energy metabolism and gut permeability. The hepatic and metabolic benefits induced by coffee were accompanied by changes in the gut microbiota.
Source : Journal of Nutritional Science
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A Compound of Chinese Herbs Protects against Alcoholic Liver Fibrosis in Rats via the TGF-β1/Smad Signaling Pathway
Xiaomeng Li,1,2 Yunjie Liu,1,2 Wuyang Yue,1,2 Yuefeng Tan,1,2 He Wang,1,2Lishi Zhang,1,2 and Jinyao Chen
Abstract
Alcoholic liver fibrosis (ALF) has become a major public health concern owing to its health impacts and the lack of effective treatment strategies for the disease. In this study, we investigated the effect of a compound composed of Chinese herbs Pueraria lobata (Willd.), Salvia miltiorrhiza, Schisandra chinensis, and Silybum marianum on ALF. An ALF model was established. Rats were fed with modified Lieber–Decarli alcohol liquid diet and injected with trace CCl4 at late stage. The rats were then treated with several doses of the compound. Biochemical and fibrosis-relevant parameters were measured from the sera obtained from the rats. Liver tissues were obtained for hematoxylin and eosin and Masson’s trichrome staining. Matrix metalloproteinase-13 and tissue inhibitor of metalloproteinase-1 were determined by immunohistochemistry assays. The mRNA and protein expression levels of transforming growth factor-β1 (TGF-β1), Smad2, Smad3, and Smad7 on the livers were also measured by quantitative polymerase chain reaction and Western blot. Results showed that the compound treatment alleviated pathological lesions in the liver, decreased the serum levels of hyaluronan, laminin, and hydroxyproline, and diminished the expression of hepatic tissue inhibitor of metalloproteinase-1. Compound treatment also increased hepatic matrix metalloproteinase-13 expression and inhibited the TGF-β1/Smad signaling pathway. In conclusion, the compound has a protective effect against ALF in rats, and an underlying mechanism is involved in the TGF-β1/Smad signaling pathway.
Source Journal Evidence Based Complementary and Alternative Medicine
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Coffee consumption and liver-related hospitalizations and deaths in the ARIC study
Emily A. Hu, Mariana Lazo, Elizabeth Selvin, James P. Hamilton, Morgan E. Grams, Lyn M. Steffen, Josef Coresh & Casey M. Rebholz
Abstract
Background/Objectives
Coffee consumption has been found to be associated with reduced risk of chronic conditions such as liver disease. However, less is known about the association between coffee and liver-related hospitalizations and deaths.
Subjects/Methods
We conducted a prospective analysis on 14,208 participants aged 45–64 years from the Atherosclerosis Risk in Communities (ARIC) study. Coffee consumption (cups/day) was assessed using food frequency questionnaires at visit 1 (1987–89) and visit 3 (1993–95). Liver-related hospitalizations were defined as a hospitalization with any International Classification of Diseases, Ninth Revision (ICD-9) code related to liver disease identified through cohort surveillance. Liver-related death was defined as any death with a liver disease ICD-9 code listed anywhere on the death certificate form.
Results
There were 833 incident cases of liver-related hospitalizations over a median follow-up of 24 years and 152 liver-related deaths over a median follow-up of 25 years. Participants who were in the highest category of coffee consumption (≥ 3 cups/day) were more likely to be men, whites, current smokers, and current alcohol drinkers. In our fully adjusted model, consuming ≥ 3 cups/day of coffee was significantly associated with a reduced risk of liver-related hospitalizations compared with never drinkers (hazard ratio: 0.79, 95% CI: 0.63–0.99). There were no significant associations between coffee consumption and liver-related deaths after adjusting for covariates.
Conclusions
Coffee drinkers may be at lower risk for liver-related hospitalizations. This supports current evidence that low and moderate levels of coffee may be protective to the liver.
Source: European Journal of Clinical Nutrition
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Curcumin attenuates hepatic fibrosis and insulin resistance induced by bile duct ligation in rats
Azam Eshaghian1 , Ameneh Khodarahmi1 , Fatemeh Safari2 , Fariba Binesh3 and Ali Moradi1 *
1 Department of Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, 8915173149, Iran
2 Department of Physiology, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, 8915173149, Iran
3 Department of Pathology, Shahid Sadoughi University of Medical Sciences, Yazd, 8915173149, Iran
Abstract
Recent studies have strongly indicated the hepatoprotective effect of curcumin; however, the precise mechanisms are not well understood. This study aimed to determine the protective effect of curcumin on hepatic damage and hepatic insulin resistance in biliary duct ligated (BDL) fibrotic rat model. To accomplish this, male Wistar rats were divided into four groups (eight for each): sham group, BDL group, sham + Cur group and BDL + Cur group. The last two groups received curcumin at a dose of 100 mg/kg daily for 4 weeks. The mRNA/protein expression levels of Ras-related C3 botulinum toxin substrate 1 (Rac1), Rac1-GTP, dinucleotide phosphate oxidase 1 (NOX1), signal transducer and activator of transcription 3 (STAT3), suppressor of cytokine signalling 3 (SOCS3), insulin receptor substrate 1 (IRS1), extracellular signalregulated kinase 1 (ERK1), specific protein 1 (Sp1) and hypoxia-inducible factor-1α (HIF-1α) were measured by real-time PCR and Western blotting, respectively. Fasting blood glucose, insulin and Leptin levels were determined and homoeostasis model assessment-estimated insulin resistance, as an index of insulin resistance, was calculated. Curcumin significantly attenuated liver injury and fibrosis, including amelioration of liver histological changes, reduction of hepatic enzymes, as well as decreased expression of liver fibrogenesis-associated variables, including Rac1, Rac1-GTP, NOX1, ERK1, HIF-1α and Sp1. Curcumin also attenuated leptin level and insulin resistance, which had increased in BDL rats (P<0·05). Furthermore, compared with the BDL group, we observed an increase in IRS1 and a decrease in SOCS3 and STAT3 expression in the curcumin-treated BDL group (P <0·05), indicating return of these parameters towards normalcy.
therapeutic option.
Source : British Journal of Nutrition via Sci-hub
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Protective effects of saffron extract and crocin supplementation on fatty liver tissue of high-fat diet-induced obese rats
- Maryam Mashmoul,
- Azrina AzlanEmail author,
- Norhafizah Mohtarrudin,
- Barakatun Nisak Mohd Yusof,
- Huzwah Khaza’ai,
- Hock Eng Khoo,
- Mehdi Farzadnia and
- Mohammad Taher Boroushaki
Abstract
Background Saffron is the dried stigma of Crocus sativus L. flower which commonly used as a natural remedy to enhance health and even fights disease in the Middle-East and Southeast Asian countries.
Methods This study was aimed to investigate protective effect of saffron extract and crocin in fatty liver tissue of high-fat diet induced obese rats. A total of 36 healthy male Sprague Dawley rats were divided into six groups. Two groups served as controls, a normal diet (ND) and a high-fat diet (HFD). The other four groups were each supplemented with saffron extract and crocin at concentrations of 40 and 80 mg/kg body weight/day for 8 weeks. All groups except ND were fed with HFD until end of the study. At baseline, blood sample was collected for determination of levels of hepatic marker enzymes, including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatise and albumin. Liver sample was collected, weighed and stained with haematoxylin and eosin for further histopathological examination.
Results Saffron extract and crocin at concentrations of 40 and 80 mg/kg had dose-dependently alleviated levels of liver enzymes and histopathological changes in diet-induced obese rat model compared to control (HFD group).
Conclusion This study suggested that saffron extract and crocin supplements have hepatoprotective effect against non-alcoholic fatty liver disease and HFD-induced liver damage.
Source : BMC Complementary and Alternative Medicine
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The Therapeutic Effect of Berberine in the Treatment of Nonalcoholic Fatty Liver Disease: A Meta-Analysis
Xiaoyun Wei,1 Chunyan Wang,1 Shijun Hao,1 Haiyan Song,1,2 and Lili Yang1,2
1Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
2China-Canada Center of Research for Digestive Diseases (ccCRDD), Shanghai 200032, China
Abstract
Aim. To assess the efficacy of berberine in the treatment of nonalcoholic fatty liver disease through meta-analysis.
Method. We searched Embase, Pubmed, Cochrane Library, and so forth, until March 2016 for randomized controlled trials using berberine to treat NAFLD.
Result. Six randomized controlled trials involving 501 patients were included in this study. The results showed that the efficacy of reducing TC, LDL, ALT, 2hPG, and HbA1c in NAFLD patients of the berberine group were significantly higher than that of control group. The subgroup analyses on TG, AST, and FBG indicated that treatment combined with berberine decreased TG level in NAFLD patients significantly. Compared with other drugs, berberine alone decreased TG level in NAFLD patients significantly. We also conducted a descriptive analysis on insulin resistance and radiography results that berberine can improve NAFLD patients’ insulin resistance and fatty liver.
Conclusion. According to analysis result, berberine has positive efficacy on blood lipids, blood glucose, liver function, insulin resistance, and fatty liver condition of NAFLD patients. However, due to the limitation of number and quality of trials included, more clinical randomized controlled trials with high quality are needed for further verification of the efficacy of berberine on NAFLD patients.
Source : Journal Evidence Based Complementary and Alternative Medicine
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Immunomodulation and liver protection of Yinchenhao decoction against concanavalin A-induced chronic liver injury in mice
1.Shi-li Jiang (Department of Liver Cirrhosis, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China )
2.Xu-dong Hu (Department of Biology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China )
3.Ping Liu (E-institute of Shanghai Municipal Education Committee, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China )
ABSTRACT
OBJECTIVE: This study investigated the immunoregulatory and protective roles of Yinchenhao decoction, a compound of Chinese herbal medicine, in a mouse model of concanavalin A (ConA)-induced chronic liver injury.
METHODS: Female BalB/c mice were randomly divided into 4 groups: normal control, ConA model, ConA model treated with Yinchenhao decoction (400 mg/kg, orally), and ConA model treated with dexamethasone (0.5 mg/kg, orally). All treatments were given once a day for 28 d. Except of the normal control, mice received tail vein injection of ConA (10 mg/kg) on days 7, 14, 21, and 28, at 1 h after treatment with Yinchenhao decoction or dexamethasone or saline to induce chronic liver injury.
RESULTS: Repeated ConA injection induced chronic liver injury, which was evidenced by inflammatory cell infiltration and necrosis, increased serum alanine aminotranferease activities, decreased albumin levels, and an imbalanced expression of immunoregulatory genes in the liver tissues including significantly enhanced interferon-γ, interleukin-4, monocyte chemotactic protein-1, and cluster of differentiation 163 mRNA levels, and reduced tumor necrosis factor-α and interleukin-6 mRNA levels. Treatment with Yinchenhao decoction significantly reversed the ConA-induced changes in immunoregulatory gene expression in the liver tissues, reduced serum alanine aminotranferease activity, enhanced serum albumin level, and attenuated the extent of liver inflammation and necrosis. Furthermore, Yinchenhao decoction did not result in hepatocyte degeneration and spleen weight loss that were observed in mice received long-term treatment with dexamethasone.
CONCLUSION: Yinchenhao decoction treatment protected liver against the ConA-induced chronic liver damage and improved liver function, which were associated with the modulation of gene expression related to immune/inflammatory response.
Source : Journal Integrative Medicine
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Protective activity of kudzu (Pueraria thunbergiana) vine on chemically-induced hepatotoxicity: in vitro and in vivo studies
- Bo Yoon Chang,
- Dong-Sung Lee,
- Jun-Kyoung Lee,
- Youn-Chul Kim,
- Hyoung-Kwon Cho and
- Sung Yeon Kim
Abstract
Background
Kudzu (Pueraria thunbergiana) root has long been used in Traditional Chinese Medicine. However, the vine of the kudzu plant has been considered waste material. This study aimed to investigate the hepatoprotective properties of the kudzu vine.
Methods
We created 0 %, 30 %, 70 %, and 95 % ethanolic kudzu vine extracts. The isoflavone contents of kudzu vine extract were quantified by high-performance liquid chromatography. Tertiary-butylhydroperoxide (t-BHP) was added to human liver-derived HepG2 cells, and the production of reactive oxygen species was measured in the presence and absence of kudzu vine extract. Antioxidant activity was evaluated in all kudzu vine extracts using a hydroxyradical scavenging assay. Thirty-five male Sprague–Dawley rats were divided into seven groups (n = 5); two groups were not given any extract or drug, one group was treated with 50 mg/kg silymarin orally for 5 days, and the remaining four groups were respectively treated with 100 mg/kg of 0 %, 30 %, 70 %, or 95 % ethanolic extract of kudzu vine orally once daily for 5 days. On day 5 the treatment groups and one untreated group were fed 0.75 ml/kg carbon tetrachloride (CCl4) to induce liver damage. Blood and liver tissue samples were collected 24 h after CCl4 administration for measurement of plasma alanine aminotransferase and aspartate aminotransferase, and concentration of malondialdehyde and glutathione in liver tissue.
Results
Puerarin was the most abundant isoflavone in kudzu vine extract. Kudzu vine extract significantly reduced the cytotoxicity and production of reactive oxygen species induced by t-BHP in a dose-dependent manner. Treatment with 0 % and 30 % ethanolic extracts of kudzu vine significantly lowered the plasma levels of alanine aminotransferase and aspartate aminotransferase in a CCl4-induced hepatotoxicity rat model (P < 0.05). Glutathione was significantly elevated in the 30 % ethanolic extract-treated group (P < 0.05), while the malondialdehyde level in liver tissue was significantly decreased in the 0 % and 30 % ethanolic extract-treated groups (P < 0.05).
Conclusions
The kudzu vine is potentially highly beneficial in treating liver damage, as it scavenges reactive free radicals and boosts the endogenous antioxidant system.
Source : BMC Complementary and Alternative Medicine
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Hepatoprotective effect of licorice, the root of Glycyrrhiza uralensis Fischer, in alcohol-induced fatty liver disease
- Jae-Chul Jung†,
- Yun-Hee Lee†,
- Sou Hyun Kim,
- Keuk-Jun Kim,
- Kyung-Mi Kim,
- Seikwan Oh and
- Young-Suk Jung
Abstract
Background
Our previous study suggested that licorice has anti-inflammatory activity in lipopolysaccharide-stimulated microglial cells and anti-oxidative activity in tert-butyl hydroperoxide–induced oxidative liver damage. In this study, we evaluated the effect of licorice on chronic alcohol-induced fatty liver injury mediated by inflammation and oxidative stress.
Methods
Raw licorice was extracted, and quantitative and qualitative analysis of its components was performed by using LC–MS/MS. Mice were fed a liquid alcohol diet with or without licorice for 4 weeks.
Results
We have standardized 70 % fermented ethanol extracted licorice and confirmed by LC-MS/MS as glycyrrhizic acid (GA), 15.77 ± 0.34 μg/mg; liquiritin (LQ), 14.55 ± 0.42 μg/mg; and liquiritigenin (LG), 1.34 ± 0.02 μg/mg, respectively. Alcohol consumption increased serum alanine aminotransferase and aspartate aminotransferase activities and the levels of triglycerides and tumor necrosis factor (TNF)-α. Lipid accumulation in the liver was also markedly induced, whereas the glutathione level was reduced. All these alcohol-induced changes were effectively inhibited by licorice treatment. In particular, the hepatic glutathione level was restored and alcohol-induced TNF-α production was significantly inhibited by licorice.
Conclusion
Taken together, our data suggests that protective effect of licorice against alcohol-induced liver injury may be attributed to its anti-inflammatory activity and enhancement of antioxidant defense.
Source : BMC Evidence Based Complementary and Alternative Medicine
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Coffee and Caffeine Intake Are Associated with Lower Risk for Advanced Hepatic Fibrosis in Patients with Hepatitis C
Khalaf N, White D, Kanwal F, et al. Coffee and caffeine are associated with decreased risk of advanced hepatic fibrosis among patients with hepatitis C. Clin Gastroenterol Hepatol. August 2015;13(8):1521-1531.e3.
One of the most popular beverages worldwide, the consumption of coffee (Coffea arabica, Rubiaceae) is associated with a number of health benefits, including protection against the development of liver injury (hepatoprotection). Also, there is an inverse association between coffee consumption and hepatocellular carcinoma with or without chronic hepatitis C virus (HCV) infection. These authors used data from a cross-sectional study among U.S. veterans with chronic HCV infection to investigate the association between caffeinated and decaffeinated coffee, tea (Camellia sinensis, Theaceae), and soda intake and the development of HCV-related advanced liver fibrosis. Their secondary objective was to determine the extent to which insulin resistance mediates the association between caffeine intake and the severity of liver fibrosis.
The study was conducted at the Michael E. DeBakey Veterans Affairs Medical Center in Houston, Texas. Participants were veterans aged 18 to 70 years with confirmed HCV viremia who were prospectively recruited from a dedicated HCV clinic at the medical center between January 5, 2009 and November 30, 2013. The participants were not receiving antiviral therapy at the time of recruitment.
At baseline and after 12 weeks, participants underwent fasting blood draws for clinical laboratory tests, had anthropometric measurements taken, and body mass index (BMI) scores calculated. They completed a detailed questionnaire about their lifetime use of alcohol, tobacco (Nicotiana tabacum, Solanaceae), injection drugs, marijuana (Cannabis sativa, Cannabaceae), and other recreational drugs, as well as the presence of comorbid conditions, such as diabetes mellitus. All participants were scored using the Model for End-Stage Liver Disease (MELD) instrument, which assesses the severity of chronic liver disease.
The participants also provided information on their intake of caffeinated and decaffeinated coffee, tea, and carbonated soda, and their use of creamers and sweeteners. Cumulative lifetime exposure to coffee was determined by their reported daily intake in each decade of life starting with the 20s. For assessing average caffeine content, the authors estimated 137 mg for each 8 oz cup of coffee, 30 mg for each 8 oz cup of tea, 46 mg for each 12 oz can of caffeinated soda, and 0 mg for decaffeinated beverages.
The exposure variables were caffeinated and decaffeinated coffee intake, tea intake, and soda intake, and caffeine intake overall and from each beverage. The main outcome variable was advanced hepatic fibrosis as scored by using the FibroSURE test, which estimates the level of liver fibrosis and inflammation.
The study included 910 veterans with chronic HCV infection. Based on FibroSURE scores, 342 (37.6%) had advanced fibrosis (AF); the remaining 568 (62.4%) with mild fibrosis served as controls for the analysis. Most of the participants were male (98%), African-American, and chronic alcohol users. Those with AF were older (average, +1.8 years), had a higher BMI, and were more likely to have type 2 diabetes mellitus, metabolic syndrome, and higher MELD scores than the controls. Among nondiabetic participants, AF cases were more likely than controls to be insulin resistant based on a baseline fasting homeostasis model assessment-insulin resistance (HOMA-IR) score of ≥ 3. They were also more likely to have received prior HCV antiviral therapy. Though none were receiving treatment at the time of the study, all participants had detectable HCV RNA levels, confirming the presence of HCV in the blood.
In terms of liver inflammation, 252 participants (27.7%) were classified as advanced inflammatory activity cases and 658 (72.3%) were classified as mild inflammatory activity controls based on FibroSURE scores. There was no association between caffeine intake and severity of inflammation.
Most participants (54.6%) reported drinking some caffeinated coffee within the year before the study, with 47.2% drinking 1 or more cups daily. The controls had a higher average daily intake of caffeinated coffee compared with the AF cases (P=0.038) and more controls than AF cases reported drinking an average of 1 or more cups daily (P=0.045).
About 70% of participants reported drinking caffeinated tea within the preceding year; 22.7% consumed 1 or more cups daily. Tea intake, both caffeinated and decaffeinated, was not significantly different between the AF cases and controls. However, among the 413 non-coffee drinkers, caffeinated tea use was more common among controls than among AF cases (P=0.03).
There was no association between any consumption of caffeinated or decaffeinated soda and AF. Although consuming ≥ 1 can of caffeinated soda daily was significantly associated with a decreased risk for hepatic fibrosis (P=0.015), this association was reduced after adjusting for age, BMI, and alcohol use, and for MELD score and the presence of metabolic syndrome (P=0.047). And it was further attenuated when adjusted for diabetes and HOMA-IR scores (P=0.063). In addition, among the subset of non-coffee drinkers, intake of ≥ 1 can of caffeinated soda was not significant.
Overall, average daily caffeine consumption from all beverages was higher in the controls (273.8 mg) than in the AF cases (218.2 mg) (P=0.013), as was the average daily intake of caffeine from coffee (P=0.028). Caffeine was consumed mostly from coffee, followed by soda and then tea. Stratified by dose, participants consuming ≥ 100 mg caffeine daily from any source had a significantly reduced risk of AF (P=0.014), as did those consuming ≥ 100 mg caffeine daily from coffee (P=0.035); however, the association was not significant among non-coffee drinkers consuming ≥ 100 mg caffeine daily. The average daily intake of coffee in prior life decades was not significant.
There were no significant associations between AF and the use of creamers/whiteners (37% of the participants) or sweeteners (23.8% of the participants).
Among the 650 nondiabetic participants, those with a HOMA-IR value ˂ 3 (in the normal range) were significantly more likely to consume more than 100 mg of caffeine daily than were the participants with HOMA-IR values of ≥ 3 (P=0.012). This association between caffeine intake and decreased risk of insulin resistance was significant after adjusting for age, BMI, and alcohol use (P=0.022); MELD score (P=0.024); and the presence of metabolic syndrome (P=0.017).
An average daily intake of 100 mg or more of caffeine from all sources was associated with a significantly decreased risk for AF (P=0.02) after adjusting for age, alcohol use, and BMI, and after adjusting for MELD scores in a second multivariate model. In a third model, adjusting for insulin resistance minimally reduced the association; however, the association between caffeine intake and decreased risk for AF remained significant after adjusting for the presence of metabolic syndrome (P=0.014).
In this study, an average daily intake of ≥ 100 mg of caffeine was associated with a lower risk for advanced hepatic fibrosis in patients with chronic HCV infection. In non-coffee drinkers, daily caffeinated tea intake (but not caffeinated soda) was also associated with decreased risk of progressive liver disease. Overall, consuming caffeinated coffee or caffeinated tea is more beneficial for patients with HCV than consuming other caffeinated beverages or decaffeinated coffee.
"If validated in other HCV-infected populations in the United States, our results suggest that a relatively low (and therefore potentially more tolerable dose) of caffeine, particularly from caffeinated coffee and possibly from tea, may convey a substantial reduction in fibrosis progression." The authors conclude that "prospective studies are warranted to determine the optimal dose and preparation of caffeinated beverage intake that could be safely and tolerably recommended for prevention of progressive liver disease in HCV patients in routine clinical practice."
--Shari Henson
Source : American Botanical Council
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Protective effects of extracts from Pomegranate peels and seeds on liver fibrosis induced by carbon tetrachloride in rats
Xiang-lan Wei12, Ru-tang Fang3, Yong-hua Yang4, Xue-yuan Bi1, Guo-xia Ren2, A-li Luo2,Ming Zhao1* and Wei-jin Zang1*
Abstract
Liver fibrosis is a feature in the majority of chronic liver diseases and oxidative stress is considered to be its main pathogenic mechanism. Antioxidants including vitamin E, are effective in preventing liver fibrogenesis. Several plant-drived antioxidants, such as silymarin, baicalin, beicalein, quercetin, apigenin, were shown to interfere with liver fibrogenesis. The antioxidans above are polyphenols, flavonoids or structurally related compounds which are the main chemical components of Pomegranate peels and seeds, and the antioxidant activity of Pomegranate peels and seeds have been verified. Here we investigated whether the extracts of pomegranate peels (EPP) and seeds (EPS) have preventive efficacy on liver fibrosis induced by carbon tetrachloride (CCl 4 ) in rats and explored its possible mechanisms.
Source : BMC Complementary and Alternative Medicine
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Buckwheat Honey Attenuates Carbon Tetrachloride-Induced Liver and DNA Damage in Mice
Ni Cheng,1,2 Liming Wu,3 Jianbin Zheng,2 and Wei Cao1,2
Abstract
Buckwheat honey, which is widely consumed in China, has a characteristic dark color. The objective of this study was to investigate the protective effects of buckwheat honey on liver and DNA damage induced by carbon tetrachloride in mice. The results revealed that buckwheat honey had high total phenolic content, and rutin, hesperetin, and p-coumaric acid were the main phenolic compounds present. Buckwheat honey possesses super DPPH radical scavenging activity and strong ferric reducing antioxidant power. Administration of buckwheat honey for 10 weeks significantly inhibited serum lipoprotein oxidation and increased serum oxygen radical absorbance capacity. Moreover, buckwheat honey significantly inhibited aspartate aminotransferase and alanine aminotransferase activities, which are enhanced by carbon tetrachloride. Hepatic malondialdehyde decreased and hepatic antioxidant enzymes (superoxide dismutase and glutathione peroxidase) increased in the presence of buckwheat honey. In a comet assay, lymphocyte DNA damage induced by carbon tetrachloride was significantly inhibited by buckwheat honey. Therefore, buckwheat honey has a hepatoprotective effect and inhibits DNA damage, activities that are primarily attributable to its high antioxidant capacity.
Source : Evidence Based Complementary and Alternative Medcine Journal
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Yiguanjian decoction and its ingredients inhibit angiogenesis in carbon tetrachloride-induced cirrhosis mice
Ya-Ning Zhou1†, Yong-Ping Mu1†, Wen-Wei Fu1, Bing-Bing Ning1, Guang-Li Du2, Jia-Mei Chen1, Ming-Yu Sun1, Hua Zhang1, Yi-Yang Hu13, Cheng-Hai Liu13, Lie-Ming Xu1 and Ping Liu13*
Abstract
Cirrhosis is associated with angiogenesis and disruption of hepatic vascular architecture. Yiguanjian (YGJ) decoction, a prescription from traditional Chinese medicine, is widely used for treating liver diseases. We studied whether YGJ or its ingredients (iYGJ) had an anti-angiogenic effect and explored possible mechanisms underlying this process.
MethodsCirrhosis was induced with carbon tetrachloride (CCl 4 ) (ip) in C57BL/6 mice for 6 weeks. From week 4 to week 6, cirrhotic mice were randomly divided into four groups: sorafenib-treated, YGJ-treated and iYGJ-treated mice and placebo. Serum biochemistries, hydroxyproline (Hyp) content and histopathological changes of hepatic tissues were measured as were α-smooth muscle actin (α-SMA), collagen I, CD31, vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR) 2 and hypoxia-inducible factor (HIF)-1α.
ResultsBoth YGJ and iYGJ improved serum biochemistries. Changes of histopathology showed that YGJ and iYGJ reduced hepatic tissue necroinflammatory and collagen fiber deposition in cirrhosis mice. Compared to the CCl 4 treated animals, Hyp, α-SMA, collagen I, CD31, VEGF, VEGFR, and HIF-1α expression decreased in YGJ and iYGJ groups.
ConclusionsYGJ and iYGJ inhibited liver angiogenesis in cirrhotic mice treated with CCl 4 by inhibiting the HIF-1α/VEGF signaling pathway, suggesting that anti-angiogenic effects of YGJ and iYGJ are associated with improving the hepatic hypoxic microenvironment.
Source : BMC Complementary and Alternative Medicine
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A double-blinded randomized controlled trial of silymarin for the prevention of antituberculosis drug-induced liver injury
Chote Luangchosiri1, Ammarin Thakkinstian2, Sermsiri Chitphuk3, Wasana Stitchantrakul3, Supanna Petraksa1 and Abhasnee Sobhonslidsuk14*
Abstract
Background Hepatitis is a common adverse effect of antituberculosis drugs. Silymarin prevented drug-induced hepatoxicity in animals with anti-oxidative mechanisms but its effect in human has been unknown. We aimed to evaluate the efficacy of silymarin for preventing antituberculosis-drug induced liver injury (antiTB-DILI) in patients with tuberculosis.
Methods A double-blind randomized placebo-controlled trial was performed. Tuberculosis patients were randomly allocated to receive placebo or silymarin. The outcomes of interests were antiTB-DILI and the maximum liver enzymes at week 4. Antioxidative enzymes (i.e., superoxide dismutase (SOD), glutathione and malondialdehyde assays) were assessed. The risks of antiTB-DILI between the two groups were compared. A number need to treat was estimated.
Results A total of 55 out of 70 expected numbers of patients were enrolled. There were 1/27 (3.7 %) and 9/28 (32.1 %) patients who developed antiTB-DILI in the silymarin and the placebo groups. Risk reduction was 0.28 (0.10, 0.47), i.e., receiving silymarin was 28 % at lower risk for antiTB-DILI than placebo. This led to prevention of 28 patients from being antiTB-DILI among 100 treated patients. Median (IQR) of ALT levels at week 4 in the placebo and the silymarin group were 35.0 (15, 415) IU/L and 31.5 (20, 184) IU/L (p = 0.455). The decline of SOD level at week 4 in the silymarin group was less than the placebo group (p < 0.027).
Conclusions Silymarin reduced the incidence of antiTB-DILI. The benefit of silymarin may be explained from superoxide dismutase restoration. Larger clinical trials are required to confirm the result of our small study
Source : BMC Complementary and Alternative Medicine
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Hepatoprotective effect of mulberry (Morus nigra) leaves extract against methotrexate induced hepatotoxicity in male albino rat
Hend M. Tag
Abstract
Drug-induced liver injury is a major health problem that challenges not only health care professionals but also the pharmaceutical industry and drug regulatory agencies. The possible hepatoprotective effect of the administration of mulberry ethanolic extract (MUL) leaves against hepatotoxic effect of the anti-rheumatic drug, methotrexate (MTX) was evaluated in this study both vivo (using animal models) and in vitro (human hepatoma HepG2 cells).
Methods
In the in-vivo study, 20 male albino rats were equally assigned into four groups; control group received distilled water orally; MUL treated-group received 500 mg/kg/day of MUL extract; MTX treated-group was injected with a single dose of 20 mg/kg MTX intraperitoneally on the 4th day; MUL-MTX treated-group received the previously mentioned doses of MUL and MTX (both control and MUL treated groups were administered a single dose of a physiological saline i.p.). At the end of the experimental period (14 days) activities of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) as well as total serum protein (TP) and albumin (ALB) levels were evaluated to assess liver function.
Results
A marked reduction in the viability of HepG2 cells was observed after 48 h with IC 50 equal to 14.5 μg/mL of MUL administration. Treating the animals with MUL in combination with MTX mitigated liver injury, causing a significant reduction in activities of AST, ALT, ALP and LDH as compared to the MTX-group. The liver architecture revealed more or less normal appearance with the combined treatment when compared with MTX treatment alone.
Conclusions
This study recommends that the co-administration of MUL with MTX that may have therapeutic benefits against MTX-hepato-cytotoxicity.
Source BMC Complementary and Alternative Medicine
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Genistein Attenuates Nonalcoholic Steatohepatitis and Increases Hepatic PPARγ in a Rat Mode
lWarinda Susutlertpanya,1 Duangporn Werawatganon,1 Prasong Siriviriyakul,1 and Naruemon Klaikeaw2
1Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
2Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
Abstract
Nonalcoholic steatohepatitis (NASH) has become a global chronic liver disease, but no effective medicine has been proven to cure it. This study investigated the protective effects of genistein, a phytoestrogen, on NASH and examined whether it has any effect on hepatic PPARγ. Male Sprague-Dawley rats were divided into four groups: control group fed ad libitum with standard rat diet, NASH group fed ad libitum with high-fat diet to induce NASH and NASH + Gen8 group and NASH + Gen16 group fed with high-fat diet plus intragastric administration of 8 or 16 mg/kg genistein once daily. After 6 weeks, liver samples were collected to determine MDA, TNF-α, PPARγ, and histopathology. The findings were that levels of hepatic MDA and TNF-αincreased in NASH group, but 16 mg/kg genistein reduced these levels significantly. Downregulation of hepatic PPARγ was observed in NASH group, but genistein significantly upregulated the expression of PPARγin both NASH + Gen groups. The histological appearance of liver in NASH group presented pathological features of steatohepatitis which were diminished in both NASH + Gen groups. The results suggest that genistein attenuates the liver histopathology of NASH with upregulation of hepatic PPARγ, reduction of oxidative stress, and inhibition of inflammatory cytokine.
Source : Evidence Based Complementary and Alternative Medicine
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Antioxidant effects of pineapple vinegar in reversing of paracetamol-induced liver damage in mice
Nurul Elyani Mohamad1, Swee Keong Yeap2, Kian Lam Lim3, Hamidah Mohd Yusof1, Boon Kee Beh3, Sheau Wei Tan2, Wan Yong Ho4, Shaiful Adzni Sharifuddin5, Anisah Jamaluddin5, Kamariah Long5, Nik Mohd Afizan Nik Abd Rahman1 and Noorjahan Banu Alitheen1*
Abstract
Background
Pineapple (Ananas comosus) was demonstrated to be hepatoprotective. This study aims to investigate the reversing effects of pineapple vinegar on paracetamol-induced liver damage in murine model.
Methods
Pineapple juice was fermented via anaerobic and aerobic fermentation to produce pineapple vinegar. Male BALB/c mice (n = 70) were separated into 7 treatment groups (n = 10). Pineapple vinegar (0.08 and 2 mL/kg BW) and synthetic vinegar were used to treat paracetamol-induced liver damage in mice. The hepatoprotective effects were determined by serum biochemistry profiles (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and triglyceride (TG)), liver antioxidant levels (ferric-reducing ability plasma (FRAP), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), and reduced glutathione assays (GSH)) and histopathological examination with hematoxylin and eosin (H&E) staining. The effects were further evaluated by the expression levels of iNOS, NF-κB, and cytochrome P450 2E1 by quantitative real-time PCR and Western blot analyses. Vinegar samples were also tested for in vitro antioxidant (FRAP, 2,2-diphenyl-2-picrylhydrazyl (DPPH), and total phenolic content (TPC)). Soluble phenolic acid contents in the samples were identified by HPLC.
Results
Pineapple vinegar contained 169.67 ± 0.05 μg GAE/mL of TPC, with 862.61 ± 4.38 μg/mL gallic acid as the main component. Oral administration of pineapple vinegar at 2 mL/kg BW reduced serum enzyme biomarker levels, including AST (P = 0.008), ALT (P = 0.006), ALP (P= 0.002), and TG (P = 0.006) after 7 days of paracetamol treatment. Liver antioxidant levels such as hepatic glutathione (P = 0.003), SOD (P < 0.001), lipid peroxidation (P = 0.002) and FRAP (P <0.001) were restored after the treatment. Pineapple vinegar reduced the expressions of iNOS (P = 0.003) and NF-kB (P = 0.003) and the level of NO (P = 0.003) significantly. Pineapple vinegar also downregulated liver cytochrome P450 protein expression.
Conclusions
Oral administration of pineapple vinegar at 0.08 and 2 mL/kg BW reduced serum enzyme biomarker levels, restored liver antioxidant levels, reduced inflammatory factor expressions, and down regulated liver cytochrome P450 protein expression in paracetamol-induced liver damage in mice.
Source : Journal Chinese Medicine
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Anti-fatty liver effects of oils from Zingiber officinale and Curcuma longa on ethanol-induced fatty liver in rats
1. Sarah Onyenibe Nwozo (Nutritional and Industrial Research Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan 200002, Nigeria E-mail: [email protected])
2. Damilola Adeola Osunmadewa (Nutritional and Industrial Research Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan 200002, Nigeria )
3. Babatunji Emmanuel Oyinloye (Nutritional and Industrial Research Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan 200002, Nigeria )
ABSTRACT
OBJECTIVE: The present study is aimed at evaluating the protective effects of oils from Zingiber officinale (ginger) and Curcuma longa (turmeric) on acute ethanol-induced fatty liver in male Wistar rats.
METHODS: Ferric reducing antioxidant power activity and oxygen radical absorbance capacity of the oils were evaluated ex vivo. Rats were pretreated for 28 d with standard drug (Livolin Forte) and oils from Z. officinale and C. longa before they were exposed to 45% ethanol (4.8 g/kg) to induce acute fatty liver. Histological changes were observed and the degree of protection was measured by using biochemical parameters such as alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities. Serum triglyceride (TG) level, total cholesterol (TC) level and the effects of both oils on reduced gluthatione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD) and hepatic malondialdehyde (MDA) levels were estimated.
RESULTS: Oils from Z. officinale and C. longa at a dose of 200 mg/kg showed hepatoprotection by decreasing the activities of serum enzymes, serum TG, serum TC and hepatic MDA, while they significantly restored the level of GSH as well as GST and SOD activities. Histological examination of rats tissues was related to the obtained results.
CONCLUSION: From the results it may be concluded that oils from Z. officinale and C. longa (200 mg/kg) exhibited hepatoprotective activity in acute ethanol-induced fatty liver and Z. officinale oil was identified to have better effects than C. longa oil.
Source : Journal Chinese Integrative Medicine
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Hepatoprotective effect of cryptotanshinone from Salvia miltiorrhiza in D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure.
Introduction
Fulminant hepatic failure (FHF) is a life-threatening clinical syndrome and characterized by coagulopathy, jaundice and multisystem organ failure and a very high mortality, even though there is still no available therapy except liver transplantation limited by the chronic shortage of donor livers (Van Thiel et al. 2002).
D-Galactosamine (GalN) and lipopolysaccharide (LPS)-induced hepatitis in mice is a commonly used test model with endotoxemic shock and fulminant hepatic failure, which is similar to fulminant hepatic failure in clinic (Hishinuma et al. 1990). In the GalN/LPS model, LPS, as the bacterial cell wall component is used to initiate the inflammatory response. Because rodents are less sensitive to LPS exposure than humans, LPS is combined with the amino sugar GalN to sensitize the animals. In response to the infection in mammals LPS is detected by immune cells such as monocytes, macrophages and hepatic Kupffer cells (Liaskou et al. 2012). The combined exposure to GalN/LPS activates Kupffer cells to produce tumor necrosis factor (TNF)-[ALPHA], consequently results in hepatocyte apoptosis, in the early stages of the LPS-induced liver injury in GalN-sensitized mice (Jaeschke et al. 1998). Then in the later stages of liver injury neutrophils transmigrate and attack hepatocytes, and eventually cause massive hepatocyte necrosis and multiorgan failure (Ramaiah and Jaeschke 2007).
Mitogen-activated protein kinases (MAPKs) family including p38 kinase, c-Jun N-terminal kinase (JNK) and extracellular signal regulated kinase (ERK) serve to regulate diverse cellular responses to extracellular stimuli, and modulate various cellular activities including gene expression, mitosis, differentiation and cell survival/apoptosis. With regard to the regulation of MAPKs, it is well known that nuclear factor (NF)-[kappa]B is an important transcriptional factor involved in the expression of TNF-[alpha] and interleukin (IL)-1 (Aggarwal 2004). In unstimulated cells, NF-[KAPPA]B is sequestered in an inactive form in the cytoplasm bound to inhibitory I[kappa]B protein. Stimulation leads to the rapid phosphorylation, ubiquitination, and degradation of I[KAPPA]B, which frees NF-[kappa]B to translocate to the nucleus and activate the transcription of proinflammatory genes (Karin and Ben-Neriah 2000). Therefore, an insight into the regulation of signaling pathways by MAPKs and NF-[kappa]B is indispensable for developing a treatment based on their inhibition.
Despite an increasing need for agents to protect the liver from damage, much less modern medicine is reliable regarding how to protect liver from diverse risks. Therefore, intense attention has been devoted to natural sources for the prevention and treatment of various liver diseases. Components from natural products used in folk herbs are expected to be therapeutically effective and have much lower toxicity when clinically used. Recently, we screened a numbers of natural substances, which are used traditionally for liver diseases (Lian et al. 2010b; Nan et al. 2004; Wan et al. 2010). Especially, we have reported that, in murine macrophage 264.7, cryptotanshinone (CTN) effectively inhibited LPS-triggered TLR4 signaling and NF-[kappa]B downstream pathways (Li et al. 2011). Cryptotanshinone is a major active Iipid-soluble constituent of Salvia miltiorrhiza Bunge (reputed "Danshen") (Zhong et al. 2009), which is commonly used in the Traditional Chinese Medicine system. It was reported that Salvia m. ameliorates cirrhosis and portal hypertension, and also protects against doxorubicin-induced hepatic toxicity (Wagner and Ulrich-Merzenich 2013 and references therein). Cryptotanshinone possesses anti-cancer, antiinflammatory and anti-oxidative activities (Lee et al. 2009; Li et al. 2011; Tang et al. 2011). In previous research, we also found that CTN significantly increased the survival rate against LPS challenge in GalN-sensitized mice. Additionally Park et al. (2009) have reported that cryptotanshinone-containing purified extract of Salvia m. protects hepatocytes from GalN-induced liver toxicity in vitro. Those together with previous in vitro results (Li et al. 2011) intrigued us to further investigate whether cryptotanshinone could attenuate GalN/LPS-induced fulminant liver failure in mice.
Source : International Journal of Phytotherapy and Phytopharmacology
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Ginsenosides Rg1 from Panax ginseng: A Potential Therapy for Acute Liver Failure Patients?
Jinqiu Zhao, Zhengyu Shi, Shu Liu, Jiajun Li, and Wenxiang Huang
Department of Infectious Diseases, The First Affiliated Hospital, Chongqing Medical University, Yuzhong District, Chongqing 400016, China
Abstract
Acute liver failure (ALF) is a rapidly progressing critical illness with a high mortality rate. Circulating inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), play a significant role in the pathophysiology of ALF through promoting hepatocellular apoptosis. Ginsenoside Rg1, the primary active ingredient in Panax ginseng (also termed Asian or Korean ginseng), has been reported to inhibit TNF-αproduction and has been shown to significantly attenuate liver fibrosis development. Here, we assessed ginsenoside Rg1’s potential as a therapy for ALF by investigating the effect of ginsenoside Rg1 treatment on circulating inflammatory markers, hepatocellular apoptosis, and relevant apoptotic signaling pathways in a well-established murine ALF model. We found that ginsenoside Rg1 significantly reduces liver damage in a murine ALF model through inhibiting TNF-α-induced, caspase-dependent hepatocellular apoptosis. These results support the further investigation of ginsenoside Rg1 as a therapeutic candidate for ALF.
Source : Journal Evidence Based Complementary and Alternative Medicine
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Hepatoprotective Effects of Silybum marianum (Silymarin) and Glycyrrhiza glabra (Glycyrrhizin) in Combination: A Possible Synergy
Mahmood Rasool,1 Javed Iqbal,2 Arif Malik,3 Hafiza Sobia Ramzan,3 Muhammad Saeed Qureshi,3 Muhammad Asif,4 Mahmood Husain Qazi,5 Mohammad Amjad Kamal,6 Adeel Gulzar Ahmed Chaudhary,1 Mohammed Hussain Al-Qahtani,1 Siew Hua Gan,7 and Sajjad Karim1
1Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Post Box No. 80216, Jeddah 21589, Saudi Arabia
2Department of Pharmacy, University of Lahore, Pakistan
3The Institute of Molecular Biology and Biotechnology, University of Lahore, Pakistan
4Department of Biotechnology and Informatics, BUITEMS, Quetta, Pakistan
5Center for Research in Molecular Medicine, University of Lahore, Pakistan
6King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
7Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia
Abstract
Oxidative stress, lipid peroxidation, and transaminase reactions are some of the mechanisms that can lead to liver dysfunction. A time-dependent study was designed to evaluate the ability of silymarin (SLN) and glycyrrhizin (GLN) in different dosage regimens to lessen oxidative stress in the rats with hepatic injury caused by the hepatotoxin carbon tetrachloride. Wistar male albino rats ( = 60) were randomly assigned to six groups. Group A served as a positive control while groups B, C, D, E, and F received a dose of CCl4 (50% solution of CCl4 in liquid paraffin, 2 mL/kg, intraperitoneally) twice a week to induce hepatic injury. Additionally, the animals received SLN and GLN in different doses for a period of six weeks. CCl4 was found to induce hepatic injury by significantly increasing serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and thiobarbituric acid reactive substances while decreasing total protein and the activities of reduced glutathione, superoxide dismutase, and catalase. Treatment with various doses of SLN and GLN significantly reduced ALT, AST, ALP, and TBARS levels and increased GSH, SOD, and CAT levels. Our findings indicated that SLN and GLN have hepatoprotective effects against oxidative stress of the liver.
Source : Evidence Based Complementary and Alternative Medicine
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Current evidence for the hepatoprotective activities of the medicinal mushroom Antrodia cinnamomea
Patrick Ying-Kit Yue1*, Yi-Yi Wong1, Kay Yuen-Ki Wong1, Yeuk-Ki Tsoi2 and Kelvin Sze-Yin Leung2*
1 Department of Biology, Faculty of Science, Hong Kong Baptist University, Hong Kong, SAR, China
2 Department of Chemistry, Faculty of Science, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China
Abstract
Antrodia cinnamomea (AC) is an endemic mushroom species of Taiwan, and has been demonstrated to possess diverse biological and pharmacological activities, such as anti-hypertension, anti-hyperlipidemia, anti-inflammation, anti-oxidation, anti-tumor, and immunomodulation. This review focuses on the inhibitory effects of AC on hepatitis, hepatocarcinoma, and alcohol-induced liver diseases (e.g., fatty liver, fibrosis). The relevant biochemical and molecular mechanisms are addressed. Overall, this review summarizes the hepatoprotective activities in vitro and in vivo. However, there is no doubt that human and clinical trials are still limited, and further studies are required for the development of AC-related products.
Source : Journal Chinese Medicine
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Coffee and Tea May Contribute to a Healthy Liver
Your morning cup of tea or coffee may be doing more than just perking you up before work.
An international team of researchers led by Duke-NUS Graduate Medical School (Duke-NUS) and the Duke University School of Medicine suggest that increased caffeine intake may reduce fatty liver in people with non-alcoholic fatty liver disease (NAFLD).
Worldwide, 70 percent of people diagnosed with diabetes and obesity have NAFLD, the major cause of fatty liver not due to excessive alcohol consumption. It is estimated that 30 percent of adults in the United States have this condition, and its prevalence is rising in Singapore. There are no effective treatments for NAFLD except diet and exercise.
Using cell culture and mouse models, the study authors -- led by Paul Yen, M.D., associate professor and research fellow, and Rohit Sinha, Ph.D of the Duke-NUS Graduate Medical School's Cardiovascular and Metabolic Disorders Program in Singapore -- observed that caffeine stimulates the metabolization of lipids stored in liver cells and decreased the fatty liver of mice that were fed a high-fat diet. These findings suggest that consuming the equivalent caffeine intake of four cups of coffee or tea a day may be beneficial in preventing and protecting against the progression of NAFLD in humans.
The findings will be published in the September issue of the journal Hepatology.
"This is the first detailed study of the mechanism for caffeine action on lipids in liver and the results are very interesting," Yen said. "Coffee and tea are so commonly consumed and the notion that they may be therapeutic, especially since they have a reputation for being "bad" for health, is especially enlightening."
The team said this research could lead to the development of caffeine-like drugs that do not have the usual side effects related to caffeine, but retain its therapeutic effects on the liver. It could serve as a starting point for studies on the full benefits of caffeine and related therapeutics in humans.
Source : Newswise
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Antioxidant Properties of Taraxacum officinale Leaf Extract Are Involved in the Protective Effect Against Hepatoxicity Induced by Acetaminophen in Mice
Dirleise Colle,1Leticia Priscilla Arantes,1Priscila Gubert,1Sonia Cristina Almeida da Luz,2 Margareth Linde Athayde ,3Joa ̃o Batista Teixeira Rocha,1and Felix Alexandre Antunes Soares1
1Department of Chemistry, Natural and Exact Sciences Center; Departments of 2Pathology and 3Industrial Pharmacy ,Health Sciences Center; Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, Brazil
.ABSTRACT
Acetaminophen (APAP) hepatotoxicity has been related to several cases of hepatitis, cirrhosis, and hepatic transplant. As APAP hepatotoxicity is related to reactive oxygen species (ROS) formation and excessive oxidative stress, natural antioxidant compounds have been tested as an alternative therapy to diminish the hepatic dysfunction induced by APAP. Taraxacum officinale Weber (Family Asteraceae), commonly known as dandelion, is used for medicinal purposes because of its choleretic, diuretic, antioxidant, anti-inflammatory, and hepatoprotective properties. This study evaluated the hepatoprotective activity of T. officinale leaf extract against APAP-induced hepatotoxicity.T. officinale was able to decrease thiobarbituric acid–reactive substance levels induced by 200 mg/kg APAP (p.o.), as well as prevent the decrease in sulfhydryl levels caused by APAP treatment. Furthermore, histopathological alterations, as well as the increased levels of serum aspartate and alanine aminotransferases caused by APAP, were prevented by T. officinale(0.1 and 0.5 mg/mL). In addition, T. officinale extract also demonstrated antioxidant activity in vitro, as well as scavenger activity against 2,2-diphenyl-1-picrylhydrazyl and nitric oxide radicals. Our results clearly demonstrate the hepatoprotective effect of T. officinale against the toxicity induced by APAP. The possible mechanisms involved include its scavenger activities against ROS and reactive nitrogen species, which are attributed to the content of phenolic compounds in the extract.
Source : Journal of Medicinal Food
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Hepatoprotective effect of water extract from Chrysanthemum indicum L. flower
Sang Chul Jeong, Sang Min Kim, Yong Tae Jeong and Chi Hyun Song
Abstract
Chrysanthemum indicum L. flower (CIF) has been widely used as tea in Korea. This study aims to investigate the hepatoprotective effect of the hot water extract of CIF (HCIF) in in vitro and in vivo systems.
Methods Hepatoprotective activities were evaluated at 250 to 1000 mug/ml concentrations by an in vitro assay using normal human hepatocytes (Chang cell) and hepatocellular carcinoma cells (HepG2) against CCl4-induced cytotoxicity. Cytochrome P450 2E1, which is a key indicator of hepatic injury, was detected by western blot analysis using rabbit polyclonal anti-human CYP2E1 antibody. An in vivo hepatoprotective activity assay was performed at 1000 to 4000 mug/ml concentrations on CCl4-induced acute toxicity in rats, and the serum levels of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were determined by standard enzyme assays.
Results The hepatoprotective effects of HCIF significantly reduced the levels of GOT (60.1%, P = 0.000) and GPT (64.5%, P = 0.000) compared with the vehicle control group (CCl4 alone). The survival rates of HepG2 and Chang cells were significantly improved compared with the control group [82.1% (P = 0.034) and 62.3% (P = 0.002), respectively]. HCIF [50 mg/kg body weight (BW)] treatment significantly reduced the serum levels of GOT (49.5%, P = 0.00), GPT (55.5%, P = 0.00), ALP (30.8%, P = 0.000) and LDH (45.6%, P = 0.000) compared with the control group in this in vivo study. The expression level of cytochrome P450 2E1 (CYP2E1) protein was also significantly decreased at the same concentration (50 mg/kg BW; P = 0.018).
Conclusion HCIF inhibited bioactivation of CCl4-induced hepatotoxicity and downregulates CYP2E1 expression in vitro and in vivo.
Source : Chinese Medicine
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Haematological and Hepatotoxic Potential of Onion (Allium cepa) and Garlic (Allium sativum) Extracts in Rats
Enitan Seyi Samson1*, Ajeigbe Kazeem Olasunkanmi1, Josiah Sunday Joel2 and Ehiaghe Friday Alfred3
1Department of Physiology, School of Basic Medical Sciences, College of Health Sciences, Igbinedion University Okada, P.M.B. 0006, Edo state, Nigeria.
2Department of Biochemistry, School of Basic Medical Sciences, College of Health
Sciences, Igbinedion University Okada, P.M.B. 0006, Edo state, Nigeria.
3Department of Haematology, School of Clinical Medicine, College of Health Sciences, Igbinedion University Okada, P.M.B. 0006, Edo state, Nigeria.
Abstract
Aims: To evaluate and compare the effects of single and combined oral administration of fresh aqueous onion (Allium cepa) and garlic (Allium sativum) extracts at different concentrations (200mg/kg/d, 400mg/kg/d and 600mg/kg/d) on some haematological and
hepatotoxicity indicator parameters in treated rats.
Study Design: Cross-sectional nonclinical study in animal model.
Place and Duration of Study: The study was carried out at the Department of Physiology, Department of Biochemistry and Department of Haematology, College of Health Sciences, Igbinedion University Okada, Edo state, Nigeria between the month of
July and August, 2011.
Methodology: Following 30 days post-oral administration of extracts in 36 treated male albino rats as well as 4 controls, haematological parameters were determined using the Sysmex® Automated Haematology Analyzer, while serum levels of liver enzymes were evaluated using the Reflotron® Plus Auto-Analyzer and liver weight was determined using electronic sensitive weighing balance.
Results: Red blood cell count (RBC), Packed cell volume (PCV), Haemoglobin concentration (HGB), Total White blood cell count (TWBC), Absolute Count of Neutrophil (NEUT#), Absolute Count of Lymphocyte (LYM#), Absolute Count of the summation of
Monocyte, Eosinophil and Basophil (MXD#) and Platelet count (PLT) were significantly increased (P<0.05) to varied extent, except Mean cell volume (MCV), Mean cell haemoglobin (MCH) and Mean cell haemoglobin concentration (MCHC) while Alanine
aminotransferase (ALAT) and Aspartate aminotransferase (ASAT) serum levels were significantly decreased (P<0.001) and liver weight (LW) was non-significantly (P>0.05) reduced in a dose-dependent manner when compared to the control. Synergistic effect
was not observed in the haematological parameters when the two extracts were combined.
Conclusion: The results of this study reveal the haematological potential of onion and garlic extracts with no potential risk of hepatotoxicity (at the concentrations tested) as earlier anticipated. It also further confirms the higher efficacy of garlic over
that of onion, but the molecular mechanism behind their combined effect would require further investigation.
Source European Journal of Medicinal Plants, 2(4): 290-307, 2012
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