Researches      [Oxymatrine (from a Chinese herb-Ku Shen) in the treatment of chronic hepatitis B for one year: a multicenter random double-blind placebo-controlled trial]      [Article in Chinese]      Lu LG, Zeng MD, Mao YM, Wan MB, Li CZ, Chen CW, Fu QC, Wang JY, She WM, Cai X, Ye J, Zhou XQ, Wang H, Wu SM, Tang MF, Zhu JS, Chen WX.      Shanghai Institute of Digestive Diseases, Renji Hospital, Shanghai Second Medical University, Shanghai 200001 China.      OBJECTIVE: To evaluate the efficacy and safety of oxymatrine in the treatment of chronic hepatitis B. METHODS: A multicenter randomized double-blind placebo-controlled trial was conducted. A total of 144 patients with chronic hepatitis B entered the study for 52 weeks; of them 72 received oxymatrine, and 72 received a placebo. Before and after the treatment, clinical symptoms, liver function, serum hepatitis B virus markers, and adverse drug reactions were observed. RESULTS: In 144 patients, 14 were dropped and excluded due to inconsistencies in the included standard. Therefore, the efficacy and safety of 130 patients were analyzed. After being treated for 52 weeks, 70.77% of the patients in the study group had a normal ALT level, and in 43.08% and 33.33% their HBV DNA and HBeAg became negative. In the placebo group, 39.68% had normal ALT level, and 12.31% and 3.33% had their HBV DNA and HBeAg become negative. The rates of complete response and partial response in the oxymatrine group were 23.08% and 58.46%, and in the placebo group they were 3.08% and 44.62%. They were significantly higher in the oxymatrine group than in the placebo group. In the oxymatrine treated patients, 12 weeks after its withdrawal, 60.00% had a normal ALT level, 41.54% and 23.33% had both HBV DNA and HBeAg negative. In the placebo group, 31.75% had a normal ALT level, 3.08% and 1.67% had both HBV DNA and HBeAg negative. The rates of complete response and partial response in the oxymatrine group were 21.54% and 47.69%, and in the placebo group they were 0 and 41.54%. They were significantly higher in the study group than in the placebo group. The adverse reaction rates of oxymatrine in the study and the placebo group were 7.69% and 6.15%, respectively, but there was no statistical significant difference between them. CONCLUSION: Oxymatrine is an effective and safe agent for the treatment of chronic hepatitis B.      PMID: 15504289 [PubMed - in process]      Oxymatrine therapy for chronic hepatitis B: a randomized double-blind and placebo- controlled multi-center trial.      Lu LG, Zeng MD, Mao YM, Li JQ, Wan MB, Li CZ, Chen CW, Fu QC, Wang JY, She WM, Cai X, Ye J, Zhou XQ, Wang H, Wu SM, Tang MF, Zhu JS, Chen WX, Zhang HQ.      Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai Second Medical University, Shanghai 200001, China. lulungen@online.sh.cn      AIM: To evaluate the efficacy and safety of capsule oxymatrine in the treatment of chronic hepatitis B. METHODS: A randomised double-blind and placebo-controlled multicenter trial was conducted. Injection of oxymatrine was used as positive-control drug. A total of 216 patients with chronic hepatitis B entered the study for 24 weeks, of them 108 received capsule oxymatrine, 36 received injection of oxymatrine, and 72 received placebo. After and before the treatment, clinical symptoms, liver function, serum hepatitis B virus markers, and adverse drug reaction were observed. RESULTS: Among the 216 patients, six were dropped off, and 11 inconsistent with the standard were excluded. Therefore, the efficacy and safety of oxymatrine in patients were analysed. In the capsule treated patients, 76.47% became normal in ALT level, 38.61% and 31.91% became negative both in HBV DNA and in HBeAg. In the injection treated patients, 83.33% became normal in ALT level, 43.33% and 39.29% became negative both in HBV DNA and in HBeAg. In the placebo treated patients, 40.00% became normal in ALT level, 7.46% and 6.45% became negative both in HBV DNA and in HBeAg. The rates of complete response and partial response were 24.51% and 57.84% in the capsule treated patients, and 33.33% and 50.00% in the injection treated patients, and 2.99% and 41.79% in the placebo treated patients, respectively. There was no significance between the two groups of patients, but both were significantly higher than the placebo. The adverse drug reaction rates of the capsule, injection and placebo were 7.77%, 6.67% and 8.82%, respectively. There was no statistically significant difference among them. CONCLUSION: Oxymatrine is an effective and safe agent for the treatment of chronic hepatitis B.      Publication Types:      •  Clinical Trial      •  Multicenter Study      •  Randomized Controlled Trial      PMID: 14606080 [PubMed - indexed for MEDLINE]      Effects of oxymatrine on the serum levels of T helper cell 1 and 2 cytokines and the expression of the S gene in hepatitis B virus S gene transgenic mice: a study on the anti- hepatitis B virus mechanism of oxymatrine.      Dong Y, Xi H, Yu Y, Wang Q, Jiang K, Li L.      Department of Infectious Disease, Peking University First Hospital, Beijing, China. dongyuhong@hotmail.com       Oxymatrine has been shown to have a remarkable inhibitory activity to hepatitis B virus (HBV) infection with a hepatitis B virus e antigen (HBeAg) serum conversion rate of approximately 45%. In order to explore the anti-HBV mechanism of oxymatrine, the effects of oxymatrine on serum levels of T helper (h)1 cytokines (interferon (IFN)-gamma and interleukin (IL)-2) and Th2 cytokines (IL-4 and IL-10), and the expression of S gene in HBV S gene transgenic mice were studied. METHODS: Each transgenic mouse was either injected with oxymatrine or saline intraperitoneally once a day for 30 days. Serum levels of IFN- gamma, IL-2, IL-4 and IL-10 were quantitated and compared to the data before the treatment. The expression of HBV S gene in transgenic mice was analyzed at the DNA, mRNA and protein levels. RESULTS: The serum levels of IFN-gamma in transgenic mice before or after oxymatrine treatment were 3.108 +/- 3.172 and 11.059 +/- 6.971 pg/mL, respectively. In contrast, serum levels before and after oxymatrine treatment for IL-4 were 29.045 +/- 13.235 and 13.024 +/- 9.002 pg/mL, respectively (P < 0.001). The serum levels of IL-2 in the control (saline injection) and oxymatrine-treated mice were 1.070 +/- 0.447 and 5.537 +/- 2.887 pg/mL, respectively (P < 0.0001); and that of IL-10 were 97.226 +/- 73.306 and 33.607 +/- 23.154 pg/mL, respectively (P < 0.01). No significant differences were observed in the expression of HBV S gene in the transgenic mice at the DNA, mRNA and protein levels before or after oxymatrine treatment. CONCLUSIONS: The fact that Th1 cytokines are increased while Th2 cytokines are decreased suggests that oxymatrine treatment triggers the change of immune response to hepatitis B infection in transgenic mice, which leads to improved HBV inhibitory activities. The study can help us better understand the mechanisms of the anti-HBV drug, oxymatrine, and how it has potential as an application in clinical chronic hepatitis B treatment. Copyright 2002 Blackwell Publishing Asia Pty Ltd      PMID: 12423275 [PubMed - indexed for MEDLINE]      [Preliminary study on therapeutic effect of oxymatrine in treating patients with chronic hepatitis C]      Li J, Li C, Zeng M.      Renji Hospital of Shanghai, Second Medical University, Shanghai 200001.      OBJECTIVE: To evaluate the efficacy of oxymatrine in treating chronic hepatitis C and its mechanism. METHODS: Forty-three patient were divided randomly into the treated group (20 cases) and the control group (23 cases). The treated group was given oxymatrine 600 mg per day intramuscularly, and the control group was given the general liver protective agents such as vitamins. The therapeutic course of both groups was 3 months. RESULTS: HCVRNA of 8 in 17 cases (47.1%) of the treated group converted to negative, while in 18 cases of the control group, the negative conversion only took place in 1 patient (5.6%), the negative conversion rate was significantly higher in the treated group than that in the control group (P < 0.05). The normalization rates of serum alanine transaminase (ALT) of the treated group after 1 month and 2 months treatment was higher than that of the control group, but after 3 months treatment, the normalization rates of the two groups were not different significantly. Plasma level of soluble interleukin-2 receptor and serum level of collagen type IV in the treated group were lowered significantly after treatment, but in the control group, there were no significant change, the difference between the two groups was significant (P < 0.01, P < 0.05). CONCLUSION: Oxymatrine is effective in inhibiting proliferation of HCV, antagonisting liver fibrosis and regulating immune reaction of the host, so it could be a safe, effective drug in treating chronic hepatitis C.      Publication Types:      •  Clinical Trial      •  Randomized Controlled Trial      PMID: 11475748 [PubMed - indexed for MEDLINE]      [The inhibitory effect of oxymatrine on hepatitis C virus in vitro]      Chen Y, Li J, Zeng M, Lu L, Qu D, Mao Y, Fan Z, Hua J.      Shanghai Institute of Digestive Diseases, Renji Hospital, Shanghai Second Medical University, Shanghai 200001, China.      OBJECTIVE: To study the inhibitory effect of oxymatrine on HCV in vitro. METHODS: SMMC-7721 cells transfected with pBK-HCV using lipofectin transfection protocal were treated with oxymatrine. bDNA signal amplification assay and MTT colorimetric assay were used for intracellular HCV RNA and cytotoxicity. RESULTS: The stable HCV expression cell model established here could be used as a tool for medicine screen. Oxymatrine at the concentration of 100~1000 mug/ml could significantly decrease the level of intracellular HCV RNA. No cytotoxicity was shown in such concentrations. CONCLUSIONS: Oxymatrine has an anti-HCV potential activity in vitro.      PMID: 11509127 [PubMed - indexed for MEDLINE]      Capsule oxymatrine in treatment of hepatic fibrosis due to chronic viral hepatitis: a randomized, double blind, placebo-controlled, multicenter clinical study.      Mao YM, Zeng MD, Lu LG, Wan MB, Li CZ, Chen CW, Fu QC, Wang JY, She WM, Cai X, Ye J, Zhou XQ, Wang H, Wu SM, Tang MF, Zhu JS, Chen WX, Zhang HQ.      Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai Second Medical University, Shanghai 200001, China. maoyimin1@sina.com      AIM: To evaluate the efficacy and safety of oxymatrine capsule in treatment of hepatic fibrosis in patients with chronic viral hepatitis. METHODS: It was a randomized, double blind, placebo-controlled, multicenter clinical study. One hundred and forty-four patients were divided into oxymatrine capsule group(group A) and placebo group (group B).The course was 52 wk. Patients were visited once every 12 wk and the last visit was at 12 wk after cessation of the treatment. All patients had liver biopsy before treatment. part of them had a second biopsy at the end of therapy. Clinical symptoms, liver function test, serum markers of hepatic fibrosis were tested. Ultrasound evaluation was performed before, during and at the end of therapy. RESULTS: One hundred and forty-four patients enrolled in the study. Of them 132 patients completed the study according to the protocol,49 patients had liver biopsy twice (25 patients in group A and 24 in group B). At the end of therapy, significant improvements in hepatic fibrosis and inflammatory activity based on Semi-quantitative scoring system (SSS) were achieved in group A. The total effective rate of the treatment was 48.00%, much higher than that of 4.17% in group B (P<0.05). Significant improvement in serum markers of hepatic fibrosis such as hyaluronic acid (HA) and type III procollagenic peptide (P III P) in group A was seen (P<0.05). The total effective rate of serum markers at the end of therapy in group A was 68.19%, much higher than that of 34.85% in group B (P<0. 05). The total effective rate of noninvasive markers at the end of therapy in group A was 66.67%, much higher than that of 30.30% in group B (P<0.05). The rate of adverse events was similar in two groups. CONCLUSION: Oxymatrine capsule is effective and safe in treatment of hepatic fibrosis due to chronic viral hepatitis.      Publication Types:      •  Clinical Trial      •  Multicenter Study      •  Randomized Controlled Trial      PMID: 15484298 [PubMed - indexed for MEDLINE]      [Prophylactic and therapeutic effect of oxymatrine on D-galactosamine-induced rat liver fibrosis]      Yang W, Zeng M, Fan Z, Mao Y, Song Y, Jia Y, Lu L, Chen CW, Peng YS, Zhu HY.      Shanghai Digestive Disease Institute, Renji Hospital, Shanghai 200001, China.      OBJECTIVE: To investigate the prophylactic and therapeutic effect of oxymatrine on experimental liver fibrosis and to reveal its mechanism. METHODS: By establishing D- galactosamine-induced rat liver fibrosis model, we observed the effect of oxymatrine on serum and tissue biochemical indexes, content of liver hydroxyline, expression of TGF?1 mRNA and changes of tissue pathology. RESULTS: There was a decline of liver hydroxyline and serum AST and ALT in oxymatrine group compared to those of the D-GalN group. The hydroxyline content in oxymatrine pretreatment group was (0.50 0.11)mug/mg compared with (0.99 0.14)mug/mg in D-GalN group (t=8.366, P<0.01). The content in oxymatrine treatment group was (0.44 0.04)mug/mg compared with 0.70 0.06 in D-GalN group (t=9.839, P<0.01). The SOD activity was (149.81 15.28) NU/mg in oxymatrine pretreatment group and (95.22 16.33) NU/mg in the model group (t=7.309, P<0.01); (157.68 19.54) NU/mg in the treatment group compared with (119.88 14.94) NU/mg in the model group (t=4.348, P<0.01). MDA in the pretreatment group was (2.06 0.17) nmol/mg, lower than (4.57 0.37) nmol/mg in the model group (t=17.529, P<0.01). In the treatment group, it was (1.76 0.24)nmol/mg, lower than (3.10 0.17) nmol/mg in the model group (t=12.697, P<0.01). TGF?1 mRNA reduced in the pretreatment and treatment groups as compared with that in the model group (0.21 0.01 vs 0.50 0.01, t=48.665, P<0.01; 0.18 0.02 vs 0.38 0.01, t=22.464, P<0.01). Electron microscopy showed that oxymatrine group had milder hepatocyte degeneration and less fibrosis accumulation than did the model group. Microscopy revealed wide septa expansion from the portal area to the central venous, piecemeal and confluent necrosis and pseudo- nodular formation in part of the lobular in the model group. While in oxymatrine group these lesions were much improved. CONCLUSIONS: Oxymatrine shows prophylactic and therapeutic effect in D-galactosamine induced rat liver fibrosis. This is partly by protecting hepatocyte and suppressing fibrosis accumulation through anti-lipoperoxidation.      PMID: 12113677 [PubMed - indexed for MEDLINE]

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