Research - Ulcerative colitis
Regulatory effects of glycyrrhizae radix extract on DSS-induced ulcerative colitis
- Yong-Deok Jeon,
- Keuk-Soo Bang,
- Min-Kyoung Shin,
- Jong-Hyun Lee,
- Young-Nam Chang and
- Jong-Sik Jin
Background Glycyrrhizae Radix (GR) is a Korean traditional herb medicine that is widely-used in clinical health care. The clinical functions of GR include relief of toxicity, anti-cancer, regulating blood cholesterol and anti-inflammation. This study investigated the role of GR on ulcerative colitis in a dextran sulfate sodium (DSS)-induced mouse model of colitis.
Method Western blot analysis and enzyme-linked immunosorbent assay (ELISA) analyses were done on male BALB/c mice administered 5 % DSS during the experimental period. Ethanol extracts of GR were orally administered at same time daily to control mice. The severity of colitis was measured by body weight change and colon length.
ResultDSS-treated mice displayed weight loss and shortened colon length compared with control mice. Mice were administered GR showed less weight loss and longer colon length than the DSS-treated group. Inflammatory cytokines were decreased by GR treatment. Treatment also reduced DSS-induced microscopic damage to colon tissue. GR regulated the phosphorylation of transcription factors such as NF-κB p65 and IκB α.
ConclusionsGR has beneficial effects in a colitis model. GR might be a useful herb medicine in the treatment of ulcerative colitis.
Source : BMC Complementary and Alternative Medicine
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Qing-dai powder promotes recovery of colitis by inhibiting inflammatory responses of colonic macrophages in dextran sulfate sodium-treated mice
Hai-Tao Xiao12, Jiao Peng3, Dong-Dong Hu14, Cheng-Yuan Lin1, Bin Du1, Siu-Wai Tsang1,Ze-si Lin15, Xiao-Jun Zhang16, Feng-Ping Lueng1, Quan-Bin Han1 and Zhao-Xiang Bian1*
Qing-dai powder (QDP), comprising Indigo naturalis (Qing-dai) and dried alum (Ku-fan), was used in Chinese medicine to treat the conditions associated with mucosal hemorrhage, such as ulcerative colitis (UC). This study aims to investigate the effects and potential mechanism of QDP on dextran sulfate sodium (DSS)-induced acute colitis in mice and to examine the regulatory effects of QDP on macrophages.
Seven- to eight-week-old male C57BL/6 mice were challenged with 2.0 % DSS in drinking water for 5 days and then the colitic mice were arbitrarily allocated into five groups (n = 10 for each group). QDP (0.77, 1.54 and 3.08 g/kg) and sulfasalazine (SASP) (0.20 g/kg) were orally administered for 7 days. The disease activity index was determined by scores of body weight loss, diarrhea and rectal bleeding; histological signs of damage was analyzed by H&E staining; myeloperoxidase activity was measured by colorimetric method, levels of proinflammatory cytokines were determined by ELISA; changes in macrophages in the colon were analyzed by immunohistochemistry (IHC) and flow cytometry. Lipopolysaccharide (LPS)-induced RAW264.7 cells were treated with or without QDP, then the production of TNF-α and IL-6 were measured by ELISA; and protein molecules such as COX-2, iNOS, IкB-α were determined by Western blot.
Oral administration of QDP at dosages of 1.54 and 3.08 g/kg significantly reduced disease activity index on day 12 (P < 0.001 for 1.54 g/kg and P < 0.0008 for 3.08 g/kg), colon shortening (P = 0.012 for 1.54 g/kg, P = 0.001 for 3.08 g/kg), histological damage (P < 0.001 for 1.54 g/kg,P < 0.001 for 3.08 g/kg) and colonic myeloperoxidase activity (P = 0.002 for 1.54 g/kg, P < 0.001 for 3.08 g/kg) of DSS-treated mice. Moreover, QDP treatment (1.54 and 3.08 g/kg) significantly decreased DSS-induced infiltration of macrophages, and production of TNF-α (P = 0.005 for 1.54 g/kg, P = 0.002 for 3.08 g/kg), IL-1β (P = 0.008 for 1.54 g/kg, P = 0.002 for 3.08 g/kg) and IL-6 (P = 0.011 for 1.54 g/kg, P = 0.004 for 3.08 g/kg) in colonic tissues, and also reduced serum MCP-1 levels (P = 0.001 for 1.54 g/kg, P < 0.001 for 3.08 g/kg). In RAW264.7 cells, QDP significantly suppressed LPS-induced production of TNF-α and IL-6 (Both P < 0.001 for 1.0 μg/mL QDP treatment) and expression levels of COX-2 (P = 0.002 and P = 0.001 for 1 and 3 μg/mL QDP treatment, respectively) and iNOS (P < 0.001 for 3 μg/mL QDP treatment) by inhibiting IкB-α degradation (P = 0.007 and P = 0.004 for 1 and 3 μg/mL QDP treatment, respectively) and NF-кB p65 nuclear translocation.
QDP suppressed the inflammatory responses of colonic macrophages in DSS-induced UC in mice and LPS-induced RAW264.7 cells.
Source : Journal Chinese Medicine
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Amaranthus roxburghianus root extract in combination with piperine as a potential treatment of ulcerative colitis in mice
1. Sunil A. Nirmal (Department of Pharmacognosy, Pravara Rural College of Pharmacy, Loni 413736, Maharashtra, India )
2. Jayashri M. Ingale (Department of Pharmacognosy, Pravara Rural College of Pharmacy, Loni 413736, Maharashtra, India )
3. Shashikant R. Pattan (Department of Pharmaceutical Chemistry, Pravara Rural College of Pharmacy, Loni 413736, Maharashtra, India )
4. Sanjay B. Bhawar (Department of Pharmacology, Pravara Rural College of Pharmacy, Loni 413736, Maharashtra, India )
The present work was undertaken to determine the effects of Amaranthus roxburghianus Nevski. (Amaranthaceae) root alone and in combination with piperine in treating ulcerative colitis (UC) in mice.
Swiss albino mice were divided into seven groups (n = 6). Standard group received prednisolone (5 mg/kg, intraperitoneally). Treatment groups received hydroalcoholic extract of roots of A. roxburghianus (50 and 100 mg/kg, per oral) and a combination of hydroalcoholic extract of roots of A. roxburghianus (50 and 100 mg/kg, per oral) and piperine (5 mg/kg, per oral). Ulcer index, colitis severity, myeloperoxidase (MPO), malondialdehyde and glutathione were estimated from blood and tissue. Column chromatography of the extract was done and purified fractions were analyzed by gas chromatography-mass spectroscopy (GC-MS).
Treatment with the combination of hydroalcoholic extract of A. roxburghianus and piperine showed minimal ulceration, hemorrhage, necrosis and leucocyte infiltration by histopathological observation. Acetic acid increased MPO levels in blood and colon tissue to 355 U/mL and 385 U/mg, respectively. The combination of hydroalcoholic extract of A. roxburghianus (100 mg/kg) and piperine (5 mg/kg) significantly decreased MPO in blood and tissue to 182 U/mL and 193 U/mg, respectively (P < 0.05). Similarly, this combination significantly reduced malondialdehyde levels and increased glutathione levels in blood and tissue. Various phytoconstituents were detected by GC-MS.
The combination of hydroalcoholic extract of A. roxburghianus and piperine is effective in the treatment of UC and the effects are comparable with the standard drug prednisolone. 4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl, eugenol and benzene, and 1-(1,5-dimethyl-4-hexenyl)-4-methyl are reported having analgesic, anti-inflammatory, and antioxidant properties; they may play a role in the biological activity of A. roxburghianus root.
Source : Journal of Chinese Integrative Medicine
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Andrographis Extract HMPL-004 Improves Colitis Symptoms
TangT, Targan SR, Li Z-S, Xu C, Byers VS, Sandborn WJ. Randomised clinical trial:herbal extract HMPL-004 in active ulcerative colitis – a double-blindcomparison with sustained release mesalazine. Aliment Pharmacol Ther. 2011;33(2):194-202.
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. About 50% ofpatients with UC are treated with drugs that contain 5-aminosalicylic acid,including oral and rectal mesalazine, sulfasalazine, balsalazide, andolsalazine. Those for whom these drugs do not work are treated with steroids,azathioprine, or the anti-tumor necrosis factor-alpha (anti-TNF-α) agentinfliximab. Risks for infection and malignancy have been associated with thesetherapies. Andrographis (Andrographispaniculata;AP) is widely used inAsian countries to treat various inflammatory and infectious diseases. Theauthors sought to determine if HMPL-004 (Hutchison Medipharma Ltd.; Shanghai,China), an aqueous ethanolic extract of AP, could significantly decrease theactivity of UC and produce significant mucosal healing.
The8-week study, which included 120 patients, was conducted at 5 sites in Shanghai, China,between November 2005 and November 2006. Eligible patients were aged 18 to 65years, with a diagnosis of mildly to moderately active UC confirmed bycolonoscopy within 1 week of the beginning of the study.
Baselineevaluation included disease history, physical examination, complete blood count(CBC), serum chemistry, urinalysis, and C-reactive protein (CRP) test forinflammation. CBC was repeated at 4 and 8 weeks; routine laboratory assessmentsand physical examination, at 8 weeks. Clinical symptoms were assessed atbaseline and every 2 weeks by using the Chinese GastroenterologicalAssociation's (CGA's) 2001 Standard for Diagnosis of UC Symptom Score Paradigm.Mucosal healing was evaluated by colonoscopy, and histopathology was evaluatedby biopsy at baseline and at 8 weeks.
Sixtypatients were randomized to receive HMPL-004, 400 mg 3 times daily; the other60 patients received mesalazine SR granules (Etiasa®; Ethypharm Industries; France), 1500 mg 3 timesdaily. The 2 HMPL-004 lots used in this study contained 8-10% andrographolide (AG)by weight.
Allanalyses were conducted in the intention-to-treat (ITT) population—thosepatients who took 1 or more doses of study medication (53 in the HMPL-004 groupand 55 in the mesalazine group). Consequently, patients with no treatmentoutcome due to discontinuation of the study were considered to have shown noefficacy.
Althoughno other UC medications were allowed during the study, about 50% of patients ineach group had been on mesalazine at some time before the study. About half ofthose had failed to respond satisfactorily to it on at least one occasion. Apost hoc analysis revealed that 70% of patients who responded to treatment(with remission and partial remission) in both groups had not receivedmesalazine previously.
Regardingsafety, the authors report that 7 (13%) patients in the HMPL-004 group and 15(27%) patients in the mesalazine group had at least 1 adverse event. Most ofthose events were mild to moderate and probably not related to the studymedication, according to the authors.
Atweek 8, 11 (21%) patients treated with HMPL-004 and 9 (16%) patients treatedwith mesalazine were in remission. An additional cohort of 36% in both groupswas classified as being in partial remission. Overall efficacy (remission,partial remission, or improvement) was reported in 40 (76%) patients in theHMPL-004 group and 45 (82%) patients in the mesalazine group (P<0.001).
Also,at week 8, results of the colonoscopy evaluation revealed 28% remission and 74%response rates in patients treated with HMPL-004, and 24% remission and 71%response rates in those treated with mesalazine.
Ofthe patients with available biopsies at week 8, 53% in the HMPL-004 group and40% in the mesalazine group had decreased inflammation of at least 25%. Ofthose patients with CRP concentrations above the upper limit of normal atbaseline, 80% in the HMPL-004 group and 66% in the mesalazine group had CRPconcentrations within normal limits at week 8.
Theauthors conclude that both drugs significantly improved the clinical severityof UC and eliminated inflammation assessed by colonoscopy in about 25% ofpatients. The distribution between the percentage of patients who experiencedremission, partial remission, or improvement was not different between the twogroups. The limited sample size, however, did not power the study todemonstrate non-inferiority. Nevertheless, these results suggest that HMPL-004could be used as a substitute for induction therapy with mesalazine or be usedas induction therapy in patients who have a suboptimal response to mesalazine.
Source : Herbalclip (American Botanical Council)
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