Therapeutic efficacy of Traditional Chinese Medicine 319 recipe on hepatic fibrosis induced by carbon tetrachloride in rats |
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Authors: | KF Cheung DW Ye ZF Yang L Lu CH Liu XL Wang RTP Poon Y Tong P Liu YC Chen George KK Lau |
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Institution: | 1. Department of Medicine, The University of Hong Kong, HKSAR, China;2. Department of Surgery, The University of Hong Kong, HKSAR, China;3. Institute of Liver Disease, Shanghai University of Traditional Chinese Medicine, China;4. School of Chinese Medicine, The University of Hong Kong, HKSAR, China |
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Abstract: | Background/aimsHepatic fibrosis is a consequence of severe liver damage that occurs in many patients with chronic liver diseases. TCM 319 recipe is a Chinese Medicine formula which consists of six Chinese herbs. In this study, we investigated the anti-fibrotic efficacy and mechanisms of TCM 319 recipe.MethodsHepatic fibrosis in rats was induced by carbon tetrachloride (CCl4). 34 male adult SD rats were allocated into five groups (group 1—concomitant CCl4 and TCM 319 recipe for 8 weeks; group 2—CCl4 for 4 weeks and then CCl4 and TCM 319 recipe for 4 weeks; group 3—CCl4 alone for 8 weeks; group 4—TCM 319 recipe only for 8 weeks; group 5—untreated controls). After 8 weeks of treatment, serum ALT assay, liver tissue histological examination and immunostaining were carried out to examine the liver function and fibrosis degree. The expression levels of platelet derived growth factor (PDGF-B), PDGF-Rβ, and transforming growth factor-beta 1 (TGF-β1) were measured by quantitative RT-PCR and western blot.ResultsTCM 319 recipe reduced liver injury and attenuated hepatic fibrosis in group 1 compared with that in group 3. TCM 319 recipe suppressed the mRNA expression of tissue inhibitor of metalloproteinase 1 (TIMP-1). In addition, treatment with TCM 319 recipe significantly down-regulated mRNA expression of PDGF-B and PDGF-Rβ, and it also suppressed protein expression of PDGF-Rβ and TGF-β1.ConclusionsTCM 319 recipe extracts could attenuate hepatic fibrosis induced by CCl4 in rats. The anti-fibrotic effect of TCM 319 recipe is associated with the down-regulation of mRNA expression of TIMP-1, PDGF-B and PDGF-Rβ, and with the suppression of protein expression of PDGF-Rβ and TGF-β1. |
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Keywords: | TCM Traditional Chinese Medicine HSC hepatic stellate cell HCC hepatocellular carcinoma HBV hepatitis B virus HCV hepatitis C virus ECM extracellular matrix CCl4 carbon tetrachloride MMP matrix metalloproteinase TIMP tissue inhibitor of metalloproteinase ALT alanine aminotransferase AST aspartate aminotransferase α-SMA smooth muscle alpha actin β-actin beta-actin TGF-β transforming growth factor-beta PDGF platelet-derived growth factor PDGF-Rβ platelet-derived growth factor receptor beta ERK extracellular signal-regulated kinases |
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