* Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
† Shanghai Key Laboratory of Traditional Chinese Medicine, Shanghai 201203, China.
Am J Chin Med. 2017;45(5):1061-1074. doi: 10.1142/S0192415X17500574. Epub 2017 Jun 28.
Gypenosides (GPs), the predominant components of Gynostemma pentaphyllum, exert antifibrotic effects; however, the mechanisms underlying their ability to ameliorate liver fibrosis are unclear. Liver fibrosis was induced in C57BL/6 mice via subcutaneous injection of 10% carbon tetrachloride (CCl[Formula: see text] three times a week for two weeks. Then, CCl was administered in conjunction with intragastric GPs for another three weeks. For in vitro analyses, WB-F344, hepatatic progenitor cells (HPCs) were treated with transforming growth factor beta 1 (TGF-[Formula: see text]1) with or without GPs for 48[Formula: see text]h. The results showed that alanine aminotransferase (ALT) and aspartate transaminase (AST) activity, deposition of collagen, hydroxyproline content, and expression of alpha-smooth muscle actin ([Formula: see text]-SMA) and collagen type I (Col I) were significantly decreased after treatment with GPs ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text]). In the 5M CCl group, the expression of HPC markers, Sox9 and cytokeratin 19 (CK19), was significantly increased compared with the normal or GPs-treated group ([Formula: see text], [Formula: see text]). Immunostaining showed that the number of Sox9 and [Formula: see text]-SMA double-positive cells was higher in the 5M CCl group than in the normal group, but the addition of GPs caused this cell number to decrease. In WB-F344 cells, the expression of [Formula: see text]-SMA and Col I was significantly increased after treatment with TGF-[Formula: see text], whereas in the GPs treatment group, expression was markedly decreased ([Formula: see text]). The levels of TGF-[Formula: see text] and TGF-[Formula: see text]R1 were markedly reduced after GPs treatment both in vivo and in vitro. In conclusion, GPs ameliorated CCl-induced liver fibrosis via the inhibition of TGF-[Formula: see text] signaling, consequently inhibiting the differentiation of HPCs into myofibroblasts.
绞股蓝苷（GPs）是绞股蓝的主要成分，具有抗纤维化作用；然而，其改善肝纤维化的机制尚不清楚。通过每周皮下注射 10%四氯化碳（CCl[Formula: see text]三次，共两周，在 C57BL/6 小鼠中诱导肝纤维化。然后，在另一个三周的时间里，用 CCl 联合胃内 GPs 进行治疗。对于体外分析，用转化生长因子-β1（TGF-[Formula: see text]1）处理 WB-F344、肝祖细胞（HPCs），或与 GPs 一起处理 48[Formula: see text]h。结果表明，用 GPs 处理后，丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）活性、胶原沉积、羟脯氨酸含量以及α-平滑肌肌动蛋白（[Formula: see text]-SMA）和胶原 I（Col I）的表达显著降低（[Formula: see text]，[Formula: see text]，[Formula: see text]，[Formula: see text]）。在 5M CCl 组中，与正常组或 GPs 处理组相比，HPC 标志物 Sox9 和细胞角蛋白 19（CK19）的表达显著增加（[Formula: see text]，[Formula: see text]）。免疫染色显示，5M CCl 组 Sox9 和 [Formula: see text]-SMA 双阳性细胞的数量高于正常组，但加入 GPs 后，该细胞数量减少。在 WB-F344 细胞中，用 TGF-[Formula: see text]处理后 [Formula: see text]-SMA 和 Col I 的表达显著增加，而在 GPs 处理组中，表达明显减少（[Formula: see text]）。体内和体外 GPs 处理后，TGF-[Formula: see text]和 TGF-[Formula: see text]R1 的水平明显降低。总之，GPs 通过抑制 TGF-[Formula: see text]信号转导，抑制 HPC 向肌成纤维细胞分化，改善 CCl 诱导的肝纤维化。
