Effects of Mangosteen on α-SMA Expression in HSC-T6 Cells and Liver Fibrosis in Rats

山竹素對老鼠星狀細胞生成α-SMA之抑制及其對老鼠肝纖維化之預防作用

李連滋(Lain-Tze Lee) ； 劉思秀(Szu-Hsiu Liu) ； 林孟男(Meng-Nan Lin) ； 胡乃韻(Nai-Yun Hu) ； 蔡瑩霏(Ying-Fei Tsai) ； 石英珠(Ying-Chu Shih) ； 飯沼宗和(Munekazu Iinuma)

《中醫藥雜誌》 24卷2期 (2013/12) Pp. 211-222

摘要

肝發炎及氧化之壓力常為肝纖維化之導因。文獻顯示山竹素具有抗發炎、抗氧化及自由基清除作用。本研究探討山竹萃取物主要活性成份α－山竹素在老鼠肝星狀細胞（HSC-T6）的作用，進而評估山竹提取物在四氯化碳誘發老鼠肝纖維化之作用。結果顯示，α－山竹素可以降低所有纖維化刺激因子（包括：血小板原性生長因子、腫瘤壞死因子－α、轉變增長因子－β1和脂多醣）在HSC-T6細胞的刺激所導致α-SMA的生成，尤其是LPS。在老鼠四氯化碳誘發肝纖維化動物試驗上，經口先期投與100 mg/kg山竹提取物可以明顯抑制血清ALT、AST的增加並可以顯著降低纖維化的程度。此結果看出α－山竹素可以降低發炎所引起的肝纖維化。山竹提取物降低肝纖維化的機制應該是由山竹素之抑制纖維生成過程、抗發炎和抑制HSC-T6細胞系功能之綜合結果。

關鍵字

α－山竹素 ； 肝纖維化 ； 老鼠肝星狀細胞 ； α－平滑肌肌動細胞 ； 四氯化碳

並列摘要

Liver fibrosis is always proceeded by inflammation and oxidative stress. Traditionally Mangosteen is well known for its anti-inflammatory, antioxidant and free radical scavenging effects. This study investigated the effect of α-mangostin(α-MG) in immortalized rat hepatic stellate cell line (HSC-T6) and the anti-fibrotic effects of MG on carbon tetrachloride (CCl4)-induced liver fibrosis in rats.This investigation indicates that α-MG reduced all fibrosis stimulators (PDGF, TNF-α, TGF-β1, and LPS) induced smooth muscle actin (α-SMA) secretion, especially that stimulated by LPS. In vivo study showed the prophylactic administration of 100 mg/kg MG significantly inhibited the increase in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and significantly reduced the liver fibrosis scores in Sprague-awley rats. These results reveal that the administration of α-MG effectively attenuated inflammation-induced fibrosis. The mechanism of the treatment of hepatic fibrosis by MG may involve anti-fibrotic, anti-inflammatory activity and the inhibition of the function of HSC-T6 cells.

並列關鍵字

α-Mangostin ； liver fibrosis ； rat hepatic stellate cell ； α-smooth muscle actin ； carbon tetrachloride

參考文獻

Schuppan, D,Afdhal, NH(2008).Liver cirrhosis.Lancet.371,838-851.

Latella, G,Vetuschi, A,Sferra, R,Catitti, V,D'Angelo, A,Zanninelli, G(2009).Targeted disruption of Smad 3 confers resistance to the development of dimethyl nitrosamine induced hepatic fibrosis in mice.Liver. Int..29,997-1009.

Jonathan, AF(2011).Therapeutic targets in liver fibrosis.Am. J. Physiol. Gastrointest. Liver Physiol..300,709-715.

Don, CR(2009).Current and future anti-fibrotic therapies for chronic liver disease.Clin. Liver Dis..12,939-965.

Pedraza-Chaverri, J,Cárdenas-Rodríguez, N,Orozco-Ibarra, M,Pérez-Rojas, JM(2008).Medicinal properties of mangosteen (Garcinia mangostana).Food Chem. Toxicol..46,3227-3239.