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Abstract: Ethnopharmacological relevance: Chinese prescription Fufang-Liu-Yue-Qing (FLYQ) has long been employed clinically to treat chronic hepatitis B, and we have reported its beneficial effects on liver fibrosis in vitro. The present study was investigated to verify protective effects of FLYQ on liver fibrosis in a rat model and to investigate the underlying mechanisms which have not been explored yet. Materials and methods: Liver fibrosis was established by intragastric administration of 2ml/kg CCl4 twice a week for 12 weeks. During the experiment, the model group received CCl4 only, and the normal control group received an equal volume of saline. Treatment groups received not only CCl4 for 12 weeks, but also the corresponding drugs, colchicine (1.00mg/kg/day) or FLYQ (300, 150, 75mg/kg/day) from 5 to 12 weeks. Results: Analysis experiments showed that FLYQ could significantly alleviate liver injury, as indicated by decreasing levels of ALT, AST, ALP, GGT, IL-6 and TNF-α. Moreover, FLYQ could effectively inhibit collagen deposition and reduce the pathological tissue damage. Research on mechanism showed that FLYQ was able to markedly reduce lipid peroxidation, recruit the anti-oxidative defense system, promote ECM degradation by modulating the levels of TIMP-1 and MMP-2, and induce HSC apoptosis by down-regulating bcl-2 mRNA, as well as inhibit the expressions of α-SMA and TGF-β1 proteins. Conclusions: Our results show that FLYQ is effective in attenuating hepatic injury and fibrosis in the CCl4-induced rat model, which should be developed as a new drug for treatment of liver fibrosis and even cirrhosis. [Copyright &y& Elsevier]

The root of Averrhoa carambola L. (Oxalidaceae), a traditional Chinese medicine, was mainly used in ancient times in the treatment of urinary calculi, recurrent headache and joint pain. Our aims were to explore the potential therapeutic effect of the extract of Averrhoa carambola L. (Oxalidaceae) roots (EACR) against hepatic fibrosis in CCl 4 -treated rats and to understand the underlying molecular mechanism. Six groups of male Sprague Dawley rats were treated as follows: vehicle (olive oil), CCl 4 alone, CCl 4 +colchicine, CCl 4 +EACR 1.0 g/kg, CCl 4 +EACR 0.5 g/kg and CCl 4 +EACR 0.25 g/kg. At the end of the 12th week, biomarkers of liver function, liver fibrosis, hepatic oxidative stress and antioxidant status were assayed, and histopathological and immunohistochemical evaluation of liver tissue were conducted to investigate the liver damage and fibrosis degree. Furthermore, expressions of COL-1a1, α-SMA, TGF-β1, Smad2, smad3, Smad4 and TIMP2 were examined by qPCR and/or western blot. The expressions of apoptosis-related proteins were also detected using western blot analysis. EACR treatment markedly reduced the CCl 4 -induced elevation of serum aminotransferase activities, liver fibrosis indexes, and the extent of oxidative stress. EACR treatment also significantly reduced the accumulation of collagen and the immunostaining of α-SMA, TGF-β1 and Smad2, 4 and 7 in the liver of CCl 4 treated rats. In addition, EACR treatment markedly reversed the CCl 4 -induced increase in mRNA expression of COL-1a1, α-SMA, TIMP2, TGF-β1, Smad2 and Smad4 and suppressed the expressions of α-SMA, TIMP2, TGF-β1, smad2, 3 and 4, BAX and cleaved caspase-3 proteins. Meanwhile, EACR treatment also significantly elevated the mRNA expression of Smad7 and the protein expression of Smad7 and Bcl-2. These results suggest that EACR has protective activity against liver fibrosis. The anti-fibrotic activity of EACR in vivo is associated with enhanced antioxidant, apoptosis-inhibition and increased MMP-2/TIMP-2 expression ratio, and with modulation of TGF-β1/Smad signaling pathway. [ABSTRACT FROM AUTHOR]