Sho-saiko-to prevents liver fibrosis induced by bile duct ligation in rats.
Hepatic fibrosis is an over-accumulation of extracellular matrix (ECM). It is a result of an imbalance between collagen synthesis and degradation. Matrix metalloproteinase (MMP) has degradative activity against collagen, but tissue inhibitors of metalloproteinase (TIMP) control the active forms of MMP by blocking the active site of MMP. In our study, we established the bile duct ligated model (BDL) in rats to evaluate anti-fibrotic potential of Chinese medicine sho-saiko-to (TJ-9). We assessed the drug's potential in inhibiting collagen accumulation, suppressing procollagen alpha1 types (I) and (III), and TIMP-1 mRNA expression. After administration of TJ-9, hyperbilirubinemia reduced approximately four-fold when compared with BDL-untreated group. TJ-9 also significantly reduced the collagen content and fibrogenic score, as well as downregulated elevated procollagen alpha1 types (I) and (III) and TIMP-1 mRNA level. Finally, we concluded that (1) TJ-9 significantly reduced cholestasis in rats with BDL, (2) TJ-9 markedly reduced the collagen content by 50%, and (3) TJ-9 exerted its antifibrogenic effect by downregulation of the mRNA expression of procollagen alpha1 types (I) and (III), and TIMP-1 in liver tissue.
Research Institute of Chinese Medicine, a China Medical University, Taichung, Taiwan.
Ming-Ho
MH
Chen
Jung-Chou
JC
Chen
Chin-Chuan
CC
Tsai
Wen-Chuang
WC
Wang
De-Ching
DC
Chang
Chun-Ching
CC
Lin
Hsiao-Yen
HY
Hsieh
D000818:Animals; D001652:Bile Ducts / Q000601:surgery; D003094:Collagen / Q000493:pharmacokinetics*; D024042:Collagen Type I / Q000096:biosynthesis*; D024061:Collagen Type III / Q000096:biosynthesis*; D004195:Disease Models, Animal; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D008026:Ligation; D008103:Liver Cirrhosis / Q000517:prevention & control* / Q000662:veterinary; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis
D024042:Collagen Type I; D024061:Collagen Type III; D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; C461320:shosaiko-to; D003094:Collagen