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Protective effects of kaerophyllin against liver fibrogenesis in rats
Author(s) -
Lee TingFang,
Lin YunLian,
Huang YiTsau
Publication year - 2012
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2011.02625.x
Subject(s) - thioacetamide , liver injury , hepatic stellate cell , curcumin , pharmacology , aspartate transaminase , alanine transaminase , intraperitoneal injection , in vivo , chemistry , hepatic fibrosis , inflammation , tumor necrosis factor alpha , fibrosis , medicine , endocrinology , immunology , biology , biochemistry , alkaline phosphatase , microbiology and biotechnology , enzyme
Eur J Clin Invest 2012; 42 (6): 607–616 Abstract Background We previously demonstrated that kaerophyllin, a lignan, isolated from a widely used traditional Chinese herb, Bupleurum scorzonerifolium , leading to the inhibition of hepatic stellate cells (HSCs) activation in vitro . This current study evaluated the in vivo role of kaerophyllin in protecting the liver against injury and fibrogenesis caused by thioacetamide (TAA) in rats and further explored the underlying mechanisms. Materials and methods Liver fibrosis in Sprague‐Dawley rats was induced by intraperitoneal injection of TAA (200 mg/kg) twice per week for 6 weeks. Animals were divided into five groups: vehicle control, TAA control, TAA + low dose kaerophyllin, TAA + high dose kaerophyllin and TAA + curcumin groups. Kaerophyllin (10 or 30 mg/kg) or curcumin (150 mg/mL) was given by gavage twice per day consecutively for 4 weeks starting 2 weeks after TAA injection. Rat HSCs were used to investigate the anti‐inflammatory role of kaerophyllin against tumour necrosis factor α (TNF‐α) in vitro . Peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) expression was knocked down in rat HSCs using PPAR‐γ small interfering RNAs. Results Kaerophyllin significantly protected liver from injury by reducing serum aspartate transaminase and alanine transaminase levels and by improving the histological architecture and fibrosis score. In addition, kaerophyllin suppressed inflammation by reducing the mRNA of TNF‐α, interleukin‐1β ( IL‐1β ) and monocyte chemoattractant protein‐1 ( MCP‐1 ) genes. In HSCs, kaerophyllin elevated PPAR‐γ activity and reduced TNF‐α‐stimulated mRNA levels of intracellular adhesion molecule‐1 ( ICAM‐1 ), MCP‐1 and IL‐1β genes, which were reversed by small interfering RNA knockdown of PPAR‐γ gene. Conclusions Our results demonstrated that kaerophyllin protected the rat liver from TAA‐caused injury and fibrogenesis by suppressing hepatic inflammation and inhibiting HSC activation, possibly through upregulation of PPAR‐γ expression.