Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Taiwan.
J Sci Food Agric. 2011 Dec;91(15):2777-84. doi: 10.1002/jsfa.4521. Epub 2011 Jul 1.
Persistent activation of hepatic stellate cells (HSC-T6) has been known to cause liver fibrosis. In this study, our objective was to investigate the effects of chebulagic acid and chebulinic acid, two hydrolysable tannins of tropical almond (Terminalia chebula) fruits, on collagen synthesis and signal transduction in transforming growth factor-β1-stimulated HSC-T6 cells. The expression of Smad2, Smad3, Smad4, collagen I(α1)/III, and plasminogen activator inhibitor 1 (PAI-1) mRNAs was determined by reverse-transcription polymerase chain reaction and their protein levels were assessed by western blotting.
Results showed that chebulagic acid and chebulinic acid at 20 µmol L(-1) exhibited cytotoxic and anti-proliferative effects on HSC-T6 cells. They also significantly decreased the expression of Smd2, Smad3 and Smad4, and the synthesis of collagen, procollagen I (α1) and III, as well as suppressing the activation of PAI-1; these events consequently facilitated the resolution of fibrosis.
These results indicate that both chebulagic acid and chebulinic acid possess antifibrotic activity, and their mechanism of action could be through the inhibition of the Smad pathway.
已知肝星状细胞（HSC-T6）的持续激活会导致肝纤维化。在这项研究中，我们的目的是研究诃子酸和诃子酸这两种热带杏仁（Terminalia chebula）果实的可水解单宁对转化生长因子-β1 刺激的 HSC-T6 细胞胶原合成和信号转导的影响。通过逆转录聚合酶链反应测定 Smad2、Smad3、Smad4、胶原 I（α1）/III 和纤溶酶原激活物抑制剂 1（PAI-1）mRNA 的表达，并通过 Western blot 测定其蛋白水平。
结果表明，20 μmol L（-1）的诃子酸和诃子酸对 HSC-T6 细胞具有细胞毒性和抗增殖作用。它们还显著降低了 Smd2、Smad3 和 Smad4 的表达以及胶原、前胶原 I（α1）和 III 的合成，并抑制了 PAI-1 的激活；这些事件最终促进了纤维化的解决。
这些结果表明，诃子酸和诃子酸均具有抗纤维化活性，其作用机制可能是通过抑制 Smad 途径。
