title: Herbal medicine Gan‑fu‑kang downregulates Wnt/Ca2+ signaling to attenuate liver fibrogenesis in vitro and in vivo.
abstract: The present study was designed to verify the effect of the Chinese prescription Gan‑fu‑kang (GFK) on the treatment of liver fibrosis, and to investigate its underlying mechanisms. Liver fibrosis was established in rats by the subcutaneous administration of 0.5 mg/kg carbon tetrachloride (CCl4) twice a week for 8 weeks. Subsequently, the rats were divided into four CCl4 groups, which were treated daily with vehicle and GFK (31.25, 312.5 and 3,125 mg/kg/day) orally between weeks 9 and 20. The inhibitory action of GFK‑medicated serum on platelet‑derived growth factor (PDGF)‑stimulated HSC‑T6 cells was also investigated. Biochemical parameters, hydroxyproline (Hyp) content and histological changes to the liver were measured. Reverse transcription‑quantitative polymerase chain reaction, western blotting and immunohistochemistry were used to examine the expression of α‑smooth muscle actin (α‑SMA), PDGF‑BB, PDGF receptor β, collagen type I and II, and the Wnt/Ca2+ signaling pathway. The results showed that GFK significantly alleviated the histological changes, decreased the content of Hyp in the liver and improved liver function in rats. In addition, GFK and GFK‑medicated serum effectively inhibited collagen deposition, reduced the expression of α‑SMA and downregulated the Wnt/Ca2+ signaling pathway in vivo and in vitro, respectively, as well as cell viability (P<0.05). These results indicated that GFK was effective in attenuating liver injury and fibrosis through downregulation of the Wnt/Ca2+ signaling pathway.
authors.affiliation: Department of Pathophysiology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Hematology, PLA General Hospital, Beijing 100853, P.R. China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Pathophysiology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Pathophysiology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Hanshu
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Pathophysiology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Miaona
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Department of Pathophysiology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Caihua
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Cong
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects*; D002251:Carbon Tetrachloride; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005260:Female; D024022:Fibrillar Collagens / Q000032:analysis / Q000378:metabolism; D029001:Herbal Medicine; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: D004365:Drugs, Chinese Herbal; D024022:Fibrillar Collagens; C550090:gan-fu-kang; D002251:Carbon Tetrachloride