Department of Pharmacy, The Second Affiliated Hospital Of Bengbu Medical College, Hongye Road, Bengbu 233000, China.
Institute for Liver Diseases, Anhui Medical University, Meishan Road No.81, Hefei 230032, China.
Int Immunopharmacol. 2019 Jul;72:330-338. doi: 10.1016/j.intimp.2019.04.016. Epub 2019 Apr 18.
Liver fibrosis is a continuous wound-healing process, which is due to excessive deposition of extracellular matrix (ECM) caused by activated Hepatic Stellate Cells (HSCs). Geniposide (GP) is a naturally occurring iridoid glucoside and is extracted from Gardenia jasminoides Ellis. GP has long been speculated to play a vital role in the treatment of hyperlipidemia and fatty liver. Emerging evidence has demonstrated that GP may be importantly associated with the pathophysiology of liver fibrosis. Nevertheless, the fundamental mechanism is yet uncertain. This studywas designed to explore the possible mechanism for the inhibitory effect of GP on CCl-induced mice liver fibrosis. In line with several clinical reports, GP significantly reduced the levels of hyaluronic acid (HA), laminin (LN), hydroxyproline (HYP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Meanwhile, liver fibrosis was significantly alleviated by GP as indicated by decreased α-smooth muscle actin (α-SMA) expression and type I collagen alpha-1 (Col I α1) deposition. In addition, GP could reduce the cell viability (IC50 = 77.11 and 42.88 μM at 24 and 48 h respectively) and cause G2/M cell arrest of the activated HSC-T6 cells. Noteworthy, GP prominently suppressed the Sonic hedgehog (Shh) signaling pathway and it might inhibit the activation and proliferation of HSC-T6 cells through Shh signaling pathway. Taken together, the current research indicate that GP has a promising antifibrotic effect which could be partially attributed to its suppression of Shh signaling pathway. Hence GP could be employed as a promising therapeutic strategy for the treatment of clinical hepatic injury.
肝纤维化是一种连续的伤口愈合过程，是由活化的肝星状细胞（HSCs）引起的细胞外基质（ECM）过度沉积所致。京尼平苷（GP）是一种天然的环烯醚萜苷，从栀子（Gardenia jasminoides Ellis）中提取。长期以来，GP 一直被推测在治疗高脂血症和脂肪肝方面发挥着重要作用。新出现的证据表明，GP 可能与肝纤维化的病理生理学密切相关。然而，其根本机制尚不清楚。本研究旨在探讨 GP 抑制 CCl 诱导的小鼠肝纤维化的可能机制。与几项临床报告一致，GP 显著降低了透明质酸（HA）、层粘连蛋白（LN）、羟脯氨酸（HYP）、天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）的水平。同时，GP 明显减轻了肝纤维化，表现为α-平滑肌肌动蛋白（α-SMA）表达和 I 型胶原α-1（Col I α1）沉积减少。此外，GP 可降低细胞活力（IC50 值分别为 24 和 48 h 时的 77.11 和 42.88 μM）并导致活化的 HSC-T6 细胞 G2/M 期细胞阻滞。值得注意的是，GP 显著抑制了 Sonic hedgehog（Shh）信号通路，它可能通过 Shh 信号通路抑制 HSC-T6 细胞的激活和增殖。综上所述，本研究表明 GP 具有有前途的抗纤维化作用，部分归因于其对 Shh 信号通路的抑制。因此，GP 可作为治疗临床肝损伤的有前途的治疗策略。
