College of Pharmacy, Kyungsung University, Busan 48434, Korea.
School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
Nutrients. 2021 Dec 27;14(1):98. doi: 10.3390/nu14010098.
Hepatic fibrosis results from chronic liver damage and is characterized by excessive accumulation of extracellular matrix (ECM). In this study, we showed that dendropanoxide (DPX), isolated from , had anti-fibrotic effects on hepatic fibrosis by inhibiting hepatic stellate cell (HSC) activation. DPX suppressed mRNA and protein expression of α-SMA, fibronectin, and collagen in activated HSCs. Moreover, DPX (40 mg/kg) treatment significantly lowered levels of liver injury markers (aspartate aminotransferase and alanine transaminase), expression of fibrotic markers, and deposition of ECM in a carbon tetrachloride-induced mouse model. Anti-fibrotic effects of DPX were comparable to those of silymarin in a hepatic fibrosis mouse model. As a possible mechanism of anti-fibrotic effects, we showed that DPX inhibited autophagosome formation (LC3B-II) and degradation of p62, which have important roles in HSC activation. These findings suggest that DPX inhibits HSC activation by inhibiting autophagy and can be utilized in hepatic fibrosis therapy.
肝纤维化是由慢性肝损伤引起的，其特征是细胞外基质（ECM）的过度积累。在这项研究中，我们表明，从 中分离得到的 dendropanoxide (DPX) 通过抑制肝星状细胞 (HSC) 的激活对肝纤维化具有抗纤维化作用。DPX 抑制了活化的 HSCs 中 α-SMA、纤连蛋白和胶原的 mRNA 和蛋白表达。此外，DPX（40mg/kg）治疗可显著降低四氯化碳诱导的小鼠模型中的肝损伤标志物（天冬氨酸氨基转移酶和丙氨酸转氨酶）、纤维化标志物的表达和 ECM 的沉积。在肝纤维化小鼠模型中，DPX 的抗纤维化作用可与水飞蓟素相媲美。作为抗纤维化作用的可能机制，我们表明 DPX 抑制自噬体形成（LC3B-II）和 p62 的降解，这在 HSC 激活中具有重要作用。这些发现表明 DPX 通过抑制自噬来抑制 HSC 的激活，可用于肝纤维化的治疗。
