title: The Salvia miltiorrhiza monomer IH764-3 induces apoptosis of hepatic             stellate cells in vivo in a bile duct ligation-induced model of liver fibrosis.
abstract: During the process of liver fibrosis, hepatic stellate cells (HSCs) play             a critical role in the excessive production of extracellular matrix (ECM). Previous             studies have indicated that the monomer IH764-3, one of the major bioactive components             of Salvia miltiorrhiza, is able to inhibit HSC proliferation and induce the apoptosis             of activated HSCs in vitro. In the current study, we used a rat model of liver             fibrosis induced by bile duct ligation (BDL) to investigate the effect of the             monomer IH764-3 on the induction of apoptosis in HSCs in vivo. The rat model of             liver fibrosis was established by BDL. Immunohistochemical staining of α-smooth             muscle actin (α-SMA) was performed to detect HSC activation and proliferation             and HSC apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick             end labeling (TUNEL) and α-SMA immunohistochemical double staining. In addition,             the protein expression levels of focal adhesion kinase (FAK), p-FAK (Tyr397),             extracellular signal-regulated kinase (ERK) and p-ERK and the mRNA expression             levels of FAK and ERK were measured by western blotting and reverse transcription-polymerase             chain reaction (RT-PCR), respectively. The monomer IH764-3 was associated with             a significant decrease in intrahepatic fibrogenesis and collagen deposition and             attenuated the liver fibrosis induced by BDL. Immunohistochemical staining revealed             that the expression of α-SMA in the IH764-3 group was significantly decreased             compared with that in the model group (12.92±2.45 vs. 22.65±2.16%, P<0.01).             TUNEL and α-SMA immunohistochemical double staining also confirmed that IH764-3             increased the apoptotic rate of the activated HSCs (34.8±4.5 vs. 4.72±0.37%, P<0.01).             Moreover, the results revealed that IH764-3 downregulated the expression levels             of FAK, p-FAK (Tyr397), ERK and p-ERK in the liver tissue of rats with liver fibrosis.             The monomer IH764-3 ameliorates experimental liver fibrosis by inhibiting HSC             proliferation and inducing HSC apoptosis, warranting its use as a potential therapeutic             agent in the treatment of liver fibrosis.
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei                     Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute                     of Gastroenterology, Hebei 050000, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Juan
authors.initials: J
authors.lastname: Wei
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Huo
authors.forename: Shuming
authors.initials: S
authors.lastname: Fang
authors.forename: Dongmei
authors.initials: D
authors.lastname: Yao
authors.forename: Junping
authors.initials: J
authors.lastname: Gao
authors.forename: Huiqing
authors.initials: H
authors.lastname: Jiang
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001652:Bile Ducts / Q000601:surgery; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D027561:Salvia miltiorrhiza / Q000378:metabolism*
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D004365:Drugs, Chinese Herbal; C079053:IH 764-3; D012333:RNA, Messenger; D003094:Collagen; D051416:Focal Adhesion Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases