title: Anti-hepatic fibrosis effects of a novel turtle shell decoction by inhibiting hepatic stellate cell proliferation and blocking TGF-β1/Smad signaling pathway in rats.
abstract: Hepatic fibrosis (HF), a wound-healing response to a variety of chronic stimuli, is characterized by the excessive synthesis of extracellular matrix (ECM) proteins by hepatic stellate cells (HSC) and eventually the development of hepatic cirrhosis. Turtle shell pill (TSP) is a common traditional Chinese medicine used for preventing and treating HF and early hepatic cirrhosis, but its side-effects and the shortage of ingredients limit its clinical application. In addition, its mechanism of action is not clear. In the present study, we first improved the original formula of TSP to produce a novel turtle shell decoction (NTSD) with less toxicity and easier accessible materials. In a carbon tetrachloride (CCl4)-induced HF rat model, we observed that NTSD and TSP had similar effects on the improvement of liver functions in rats, including a decrease in serum alanine amino transferase (ALT) and aspartate amino transferase (AST) serum concentrations and increased albumin content in addition to a marked attenuation of CCl4-induced liver damage and fibrosis. NTSD containing rat serum inhibited rat liver stellate cell line HSC-T6 cell proliferation and induced cell apoptosis in vitro. Moreover, the NTSD treatment significantly decreased the transforming growth factor beta 1 (TGF-β1) and Smad3 gene expression and increased inhibitory Smad7 gene expression in liver tissues of HF rats, suggesting that NTSD inhibited the ECM expression of HSC by downregulating the TGF-β1/Smad signaling pathway. The results of our rat model study revealed that NTSD showed good in vitro and in vivo anti-HF effects via proliferation inhibition and the induction of apoptosis of HSCs and blocked the TGF-β1/Smad signaling pathway.
authors.affiliation: Department of Integrated Chinese and Western Medicine, Southwest Hospital, The Third Military Medical University, Chongqing 400038, P.R. China.
authors.forename: Ganping
authors.initials: G
authors.lastname: Bai
authors.affiliation: Institute of Combined Injuries, The State Key Laboratory of Trauma, Burns and Combined Injury, College of Preventive Medicine, The Third Military Medical University, Chongqing 400038, P.R. China.
authors.forename: Guohe
authors.initials: G
authors.lastname: Yan
authors.affiliation: Department of Integrated Chinese and Western Medicine, Southwest Hospital, The Third Military Medical University, Chongqing 400038, P.R. China.
authors.forename: Guojian
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Integrated Chinese and Western Medicine, Southwest Hospital, The Third Military Medical University, Chongqing 400038, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wan
authors.affiliation: Department of Integrated Chinese and Western Medicine, Southwest Hospital, The Third Military Medical University, Chongqing 400038, P.R. China.
authors.forename: Ronghua
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000187:drug effects; D006801:Humans; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D008516:Medicine, Chinese Traditional / Q000009:adverse effects*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D051900:Smad3 Protein / Q000096:biosynthesis*; D051906:Smad7 Protein / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis*; D014426:Turtles
chemical_list: D051900:Smad3 Protein; C497787:Smad3 protein, rat; D051906:Smad7 Protein; C497808:Smad7 protein, rat; D053773:Transforming Growth Factor beta1; D002251:Carbon Tetrachloride