Protective effects of kaerophyllin against liver fibrogenesis in rats

作者：Lee Ting Fang; Lin Yun Lian; Huang Yi Tsau^*

来源：European Journal of Clinical Investigation, 2012, 42(6): 607-616.

DOI：10.1111/j.1365-2362.2011.02625.x

• Bupleurum scorzonerifolium
• hepatic stellate cells
• inflammation
• kaerophyllin
• liver fibrosis
• PPAR-

Eur J Clin Invest 2012; 42 (6): 607616 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 alpha (TNF-alpha) in vitro. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) expression was knocked down in rat HSCs using PPAR-gamma 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-alpha, interleukin-1 beta (IL-1 beta) and monocyte chemoattractant protein-1 (MCP-1) genes. In HSCs, kaerophyllin elevated PPAR-gamma activity and reduced TNF-alpha-stimulated mRNA levels of intracellular adhesion molecule-1 (ICAM-1), MCP-1 and IL-1 beta genes, which were reversed by small interfering RNA knockdown of PPAR-gamma 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-gamma expression.

• 出版日期2012-6