Department of Biomedical Sciences and Engineering, Institute of Systems Biology and Bioinformatics, National Central University, Taoyuan, Taiwan.
Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan.
J Food Drug Anal. 2019 Jan;27(1):184-194. doi: 10.1016/j.jfda.2018.09.008. Epub 2018 Oct 25.
CCM111 is an aqueous extract of Antrodia cinnamomea (AC) that has exhibited anti-liver fibrosis functions. However, the detailed mechanisms of AC action against liver fibrosis have not been elucidated yet. The present research showed that CCM111 significantly lowered the levels of the hepatic enzyme markers glutamate oxaloacetate transaminase (GOT) and glutamic pyruvic transaminase (GPT), prevented liver damage and collagen deposition, and downregulated TGF-β/Smad signaling in a dose-dependent manner compared with CCl treatment alone. CCM111 markedly inhibited TGF-β, Wnt and STAT3 signaling pathway-regulated downstream genes in the liver by next-generation sequencing. The antifibrotic mechanisms of CCM111 were further demonstrated in HSC-T6 cells. Our data demonstrated for the first time that CCM111 can protect against CCl-induced liver fibrosis by the cooperative inhibition of TGF-β-, Wnt- and STAT3-dependent proinflammatory and profibrotic mediators, suggesting that CCM111 might be a candidate for preventing and treating chronic fibrotic liver diseases.
CCM111 是一种安络小皮伞（Antrodia cinnamomea，AC）的水提物，具有抗肝纤维化功能。然而，AC 抗肝纤维化的确切作用机制尚未阐明。本研究表明，与单独 CCl 处理相比，CCM111 能显著降低肝酶标志物谷氨酸草酰乙酸转氨酶（GOT）和谷氨酸丙酮酸转氨酶（GPT）的水平，防止肝损伤和胶原沉积，并呈剂量依赖性地下调 TGF-β/Smad 信号通路。下一代测序表明，CCM111 显著抑制了 TGF-β、Wnt 和 STAT3 信号通路调控的肝内下游基因。CCM111 在 HSC-T6 细胞中的抗纤维化机制进一步得到证实。我们的数据首次表明，CCM111 可以通过协同抑制 TGF-β、Wnt 和 STAT3 依赖性促炎和促纤维化介质来预防和治疗 CCl 诱导的肝纤维化，提示 CCM111 可能是预防和治疗慢性纤维性肝病的候选药物。
