title: Anti-fibrotic effects of puerarin on CCl4-induced hepatic fibrosis in rats possibly through the regulation of PPAR-γ expression and inhibition of PI3K/Akt pathway.
abstract: Hepatic fibrosis (HF) is a chronic disease, which primarily leads to liver unregulated metabolism. In this study, we aimed to investigate the therapeutic effects of puerarin (PR), an active ingredient from kudzu root, on CCl4-induced HF rats. PR effectively ameliorated the liver metabolic function, resulting in reduced serum enzymatic activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total-bilirubin (T-bilirubin), extracellular matrix (ECM) contents and increased levels of albumin, total-protein (T-protein) in HF rats. Similarly, pathological examination showed that the CCl4-lesioned liver was mitigated by PR treatments. Meanwhile, we also detected significantly reduced levels of hydroxyproline (Hyp), type III precollagen (PCIII) and collagen I (Col I) in the liver tissue of HF rats, whereas the peroxisome proliferator-activated receptor-gamma (PPAR-γ) expression was effectively increased. Moreover, the expression of tissue inhibitor of metal protease-1 (TIMP-1) was decreased, while the expression of matrix metalloproteinase-2 (MMP-2) was increased. In addition, the expression of p-PI3K and p-Akt was significantly down-regulated by PR treatments. Taken together, PR could attenuate the CCl4-induced toxicity in the hepatocytes of HF rats. It played a protective role in the liver tissue probably through regulating the PPAR-γ expression and blocking the PI3K/Akt pathway to inhibit the excessive deposition of collagen.
authors.affiliation: Guigang City People's Hospital, The Eighth Affiliated Hospital of Guangxi Medical University, Guigang, Guangxi 537100, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Guo
authors.forename: Lingyuan
authors.initials: L
authors.lastname: Xu
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: He
authors.forename: Tao
authors.initials: T
authors.lastname: Liang
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Duan
authors.forename: Rong
authors.initials: R
authors.lastname: Li
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002251:Carbon Tetrachloride / Q000009:adverse effects*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006909:Hydroxyproline / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D029908:Pueraria; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D001663:Bilirubin; D002251:Carbon Tetrachloride; D024042:Collagen Type I; D024061:Collagen Type III; D006909:Hydroxyproline; D007529:Isoflavones; D020778:Matrix Metalloproteinase 2; D047495:PPAR gamma; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D012709:Serum Albumin; D019715:Tissue Inhibitor of Metalloproteinase-1; D014665:Vasodilator Agents; C576839:TIMP1 protein, rat; C522363:Mmp2 protein, rat; C033607:puerarin