Research - Milk Thistle / Silybum marianum
Silymarin Enriched Extract (Silybum marianum) Additive Effect on Doxorubicin-Mediated Cytotoxicity in PC-3 Prostate Cancer Cells
Katerina Gioti, Anastasia Papachristodoulou, Dimitra Benaki, Sophia Havaki, Apostolos Beloukas, Argyro Vontzalidou, Nektarios Aligiannis, Alexios-Leandros Skaltsounis, Emmanuel Mikros, Roxane Tenta
Silymarin-enriched extract (SEE) is obtained from Silybum marianum(Asteraceae). Doxorubicin (DXR) is a widely used chemotherapeutical yet with severe side effects. The goal of the present study was to assess the pharmacologic effect of SEE and its bioactive components silibinin and silychristine when administrated alone or in combination with DXR in the human prostate cancer cells (PC-3). PC-3 cells were treated with SEE, silibinin (silybins A and B), silychristine, alone, and in combination with DXR, and cell proliferation was assessed by the MTT assay. Cell cycle, apoptosis, and autophagy rate were assessed by flow cytometry. Expression levels of autophagy-related genes were quantified by qRT-PCR, ELISA and western blot while transmission electron microscopy was performed to reveal autophagic structures. Finally, NMR spectrometry was used to identify specific metabolites related to autophagy. SEE inhibited PC-3 cell proliferation in a dose-dependent manner while the co-treatment (DXR-SEE) revealed an additive cytotoxic effect. Cell cycle, apoptosis, and autophagy variations were observed in addition to altered expression levels of autophagy related genes (LC3, p62, NBR1, Beclin1, ULK1, AMBRA1), while several modifications in autophagic structures were identified after DXR-SEE co-treatment. Furthermore, treated cells showed a different metabolic profile, with significant alterations in autophagy-related metabolites such as branched-chain amino acids. In conclusion, the DXR-SEE co-treatment provokes perturbations in the autophagic mechanism of prostate cancer cells (PC-3) compared to DXR treatment alone, causing an excessive cell death. These findings propose the putative use of SEE as an adjuvant cytotoxic agent.
Source : Journal Planta Medica
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In vivo anticlastogenic effect of silymarin from milk thistle Silybum marianum L.
Sirajudheen Anwar1, Hafez R Madkor2, Nafees Ahmed3, Mohamed E Wagih4
OBJECTIVE: Silymarin, extracted from the seeds of Silybum marianum L. (Milk thistle), is traditionally used for treating various illnesses such as diabetes, cancer, inflammation, hepatitis, liver cirrhosis, and renal problems. Acute cytotoxicity and genotoxicity studies have been reported with ambiguous outcomes; however, its relevant anticlastogenic potential is not yet evaluated. This study was aimed to evaluate in vivo subacute anticlastogenic properties of silymarin to validate its use as a medicinal agent.
MATERIALS AND METHODS: Silymarin was isolated from seeds of milk thistle. Various genotoxicity bioassays of silymarin were performed using mice. First, the bone marrow cell proliferation was estimated by calculating mitotic index. Second, the chromosomal abnormalities in mice bone marrow cells were studied. Third, micronucleated polychromatic erythrocytes (MPE) test and in vivo activation of sister chromatid exchanges (SCEs) were carried out in mice bone marrow cells. Finally, primary spermatocytes were analyzed to estimate genotoxic effect of silymarin on germ cells.
RESULTS: We found that silymarin is capable of inducing a significant increase (P ≤ 0.05) in cell proliferation of bone marrow cells. There is no increase in chromosomal aberrations following silymarin treatments. Results clearly showed that it significantly (P ≤ 0.05) decreased the MPE. Likewise, it was found to be a negative inducer of SCEs. It decreased in total abnormal metaphase, SCEs, MPE, and aberrant diakinesis.
CONCLUSION: The results demonstrated that silymarin has a strong anticlastogenic activity upon mice genome in somatic and germ cells, indicating its safe use as a medicinal substance. Furthermore, it is not only safe but also has protective effect from clastogens.
Source : The Indian Journal of Pharmacology
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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*
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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Oral milk thistle extract stops colorectal cancer stem cells from growing tumors
In results presented at the American Association for Cancer Research (AACR) Annual Meeting 2015, a University of Colorado Cancer Center study shows that orally administering the chemical silibinin, purified from milk thistle, slows the ability of colorectal cancer stem cells to grow the disease. When stem cells from tumors grown in silibinin-fed conditions were re-injected into new models, the cells failed to develop equally aggressive tumors even in the absence of silibinin.
“It’s very simple: tumors from mice that were initially fed silibinin had fewer cancer stem cells, were smaller, had lower metabolisms and showed decreased growth of new blood vessels. Importantly, when these cancer stem cells from tumors in mice fed silibinin were re-injected into new mice, we found these stem cells had lost their potential to repopulate even in the absence of silibinin exposure,” says Rajesh Agarwal, PhD, co-program leader of Cancer Prevention and Control at the CU Cancer Center and professor at the Skaggs School of Pharmacy and Pharmaceutical Sciences.
Silibinin is a non-toxic, potentially chemopreventive agent derived from milk thistle seeds. Results presented by Agarwal and colleagues at last year’s AACR Annual Meeting showed that, in cell cultures, silibinin affects cell signaling associated with the formation and survival of colorectal cancer stem cells. The current study extends this promising line of research into mouse models.
Specifically, the group used sorted colorectal cancer stem cells to grow tumors in mice that were either fed or not fed with silibinin. Tumor growth was measured by visible size, MRI scan and measurement of tumor metabolism (glucose use). These tumors cells either unsorted or sorted for cancer stem cells were then re-injected in mice to measure their growth pattern in next generations in the absence of silibinin feeding.
“We have been deeply involved in this line of research that extends from silibinin to its chemopreventive properties in colorectal cancer, and the current study takes another important step: we see both a likely chemopreventive and a therapeutic mechanism and the result of this mechanism in animal models,” says Sushil Kumar, PhD, postdoctoral fellow in the Agarwal Lab.
The group continues to investigate the molecular mechanisms, cell culture, and animal model effects of silibinin toward a likely human clinical trial of silibinin in cancer preventative and/or treatment settings.
Source : University of Colorado Cancer Center
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Mechanisms of Action of Phytochemicals from Medicinal Herbs in the Treatment of Alzheimerʼs Disease
Mi Hye Kim1, Sung-Hoon Kim2, Woong Mo Yang1
- 1College of Korean Medicine and Institute of Korean Medicine, Kyung Hee University, Seoul, Korea
- 2Cancer Preventive Material Development Research Center, College of Korean Medicine, Kyung Hee University, Seoul, Korea
Alzheimerʼs disease is a chronic neurodegenerative disorder characterized by progressive dementia and deterioration of cognitive function. Although several drugs currently used for the treatment of Alzheimerʼs disease delay its onset and slow its progression, still there is no drug with profound disease-modifying effects. Studies aiming the treatment of this neurodegenerative disorder explore various disease mechanisms. Since antiquity, medicinal herbs have been used in traditional medicine. Recent studies suggest that the neurobiological effects of phytochemicals from medicinal herbs may contribute to clinical benefits in in vitro and in vivo models of Alzheimerʼs disease. This review focuses on five phytochemicals, berberine, curcumin, ginsenoside Rg1, puerarin, and silibinin, which have been mostly investigated to treat the development and progression of this neurodegenerative disorder.
....To date, evidence from recent studies suggests that commonly used medicinal herbs and their phytochemicals could potentially be used to treat AD. Although these studies focus on the efficacy of inhibiting AD development, and research on humans is limited, numerous findings demonstrate the possibilities of the use of medicinal herbs for the treatment of AD. The approach to investigate the potential treatment of AD may support drug development from herbal medicine.
Source : Planta Medica
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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
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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Silibinin found in Milk Thistle Protects Against UV Induced Skin cancer
A pair of University of Colorado Cancer Center studies published this month show that the milk thistle extract, silibinin, kills skin cells mutated by UVA radiation and protects against damage by UVB radiation - thus protecting against UV-induced skin cancer and photo-aging."When you have a cell affected by UV radiation, you either want to repair it or kill it so that it cannot go on to cause cancer. We show that silibinin does both," says Rajesh Agarwal, PhD, co-program leader of Cancer Prevention and Control at the CU Cancer Center and professor at the Skaggs School of Pharmacy and Pharmaceutical Sciences.
The first study, published in the journal Photochemistry and Photobiology worked with human skin cells subjected to UVA radiation, which makes up about 95 percent of the sun's radiation that reaches Earth. The Agarwal Lab treated these UVA-affected cells with silibinin. With silibinin, the rate at which these damaged cells died increased dramatically.
"When you take human skin cells - keratinocytes - and treat them with silibinin, nothing happens. It's not toxic. But when you damage these cells with UVA radiation, treatment with silibinin kills the cells," Agarwal says, thus removing the mutated cells that can cause skin cancer and photo-aging.
Specifically, the study shows that pretreatment with silibinin resulted in higher release of reactive oxygen species (ROS) within the UVA-exposed cells, leading to higher rates of cell death.
The second study, published this month by the same authors in the journal Molecular Carcinogenesis shows that instead of beneficially killing cells damaged by UVA radiation, treatment with silibinin protects human skill cells from damage by UVB radiation, which makes up about 5 percent of the sun's radiation reaching Earth.
Again, remember Agarwal's suggestion that the prevention of UV-induced skin cancer can happen in two ways: by protecting against DNA damage or by killing cells with damaged DNA. With UVA, silibinin kills; with UVB, it protects, in this case by increasing cells' expression of the protein interleukin-12, which works to quickly repair damaged cells.
"It has been 20 years of work with this compound, silibinin," Agarwal says. "We first noticed its effectiveness in treating both skin and solid cancers, and we now have a much more complete picture of the mechanisms that allow this compound to work."
Agarwal and colleagues continue to test the effectiveness of silibinin in cancer prevention and treatment in cell lines and mouse models, and are working toward human trials of silibinin-based therapeutics.
Source : Newswise
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Silymarin Exhibits Clinically-relevant Antiallergic and Anti-inflammatory Activities
The standardised extract of St Mary’s thistle (Silybum marianum), which is typically (and perhaps inaccurately) referred to as silymarin or silymarin
extract, is widely used to treat liver problems and damage. However, two clinical trials (one recent and the other dating from 2009) have found surprising and useful antiallergic and anti-inflammatory activities. In the more recent double blind trial conducted in Iran, 94 patients suffering the signs and symptoms of allergic rhinitis and exhibiting positive skin prick tests to common aeroallergens randomly received either silymarin extract (420 mg/day) or placebo for one month.1 Routine antihistamine treatment was allowed. Only 60 patients completed the trial, dictating a perprotocol analysis of the results. Based on the Sino-Nasal Outcome Test (SNOT-20!), a significant improvement in clinical symptom severity was
observed in both groups (9.23 ± 5.14 for the silymarin group versus 2.20 ± 2.69 for the placebo group; both p < 0.001 versus baseline), but the improvement was significantly greater in the active group (p < 0.0001). Post-treatment levels of nasal eosinophils and cytokines from stimulated blood lymphocytes were unchanged. Paradoxically, there was significant rise in serum IgE after treatment with silymarin (p < 0.003).
In the 2009-published double blind clinical trial from Iraq, 220 patients with painful knee osteoarthritis (OA) were randomised into 5 groups, receiving either silymarin (300 mg/day), piroxicam (20 mg/day), meloxicam (15 mg/day) or a combination of silymarin with each of the anti-inflammatory drugs.2 There was no placebo group in the study design and treatment was over 8 weeks. Treatment with silymarin
significantly reduced serum levels of the inflammatory cytokines interleukin (IL)-1alpha (by 56%) and IL-8 (by 58%) (p < 0.02 compared with baseline) and the complement proteins C3 (by 81%) and C4 (by 45%). Adjunct use of silymarin with the drugs gave mixed
results for these measures of inflammation (no effect with meloxicam and a significant lowering with piroxicam). The drugs on their own generally exhibited minimal or adverse effects (apart from piroxicam lowering IL-8). Unfortunately, the trial did not provide data for clinical OA symptoms. An earlier publication also demonstrated that co-administered silymarin decreased the renal and hepatic toxicities of these drugs in OA patients.3
Although these uses might seem novel for silymarin, they are consistent with several in vitro and in vivo studies demonstrating various anti-inflammatory, antiallergic and immune-modulating outcomes for the herbal extract. However, results from experimental models do not necessarily reflect on clinical outcomes for herbal treatments, so the above clinical findings do add significant credibility to the use of silymarin for
allergic rhinitis (and perhaps other allergies) and OA. More studies are needed, however, especially one assessing clinical outcomes in OA.
1 Bakhshaee M, Jabbari F, Hoseini S et al. Otolaryngol Head Neck Surg 2011; 145(6): 904-909
2 Hussain SA, Jassim NA, Numan IT et al. Saudi Med J 2009; 30(1): 98-103
3 Hussain SA, Numan IT, Khalaf BH et al. Iraqi J Pharm Sci 2007;
Source : MediHerb eMonitor
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Study Shows Possible Benefit of Milk Thistle Extract for Hepatitis C Virus
Silymarin is a polyphenolic flavonoid derived from milk thistle
Recent research, funded in part by NCCAM and published in the journal Gastroenterology, has shown that an extract of the milk thistle plant may help treat hepatitis C virus infection. Hepatitis C, a liver disease caused by a virus, is usually chronic (long-lasting), with symptoms ranging from mild (or even none) to severe.
Researchers from the University of Washington School of Medicine, the Fred Hutchinson Cancer Research Center, Harvard Medical School, and the University of North Carolina used cells from healthy volunteers and those with chronic hepatitis C infection to test the effects of silymarin, an extract of milk thistle. Specifically, they tested peripheral blood nuclear cells and T cells—immune cells that multiply and increase inflammation. Results of the study showed that silymarin was able to inhibit the production and secretion of proteins called cytokines—tumor necrosis factor‑alpha, interferon‑gamma, and interleukin‑2—that trigger inflammation and respond to infections. Other extracts of milk thistle—silybin A, silybin B, and a combination of the two called silibinin—similarly inhibited cytokine production and cell production.
These findings suggest that silymarin could potentially control the inflammation that is characteristic of chronic liver disease in humans. Researchers indicated that these findings, combined with knowledge from previous studies, could lead to clinical benefits for patients with hepatitis C virus infection, but more studies are needed.
- Morishima C, Shuhart MC, Wang CC, et al. Silymarin inhibits in vitro T-cell proliferation and cytokine production in hepatitis C virus infection. Gastroenterology. 2010;138(2):671–681.
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