Lin Xing, Bai Faicheng, Nie Jinlan, Lu Shengjuan, Lu Chunyuang, Zhu Xunshuai, Wei Jinbin, Lu Zhongpeng, Huang Quanfang
Guangxi Medical University, Nanning, China.
Cell Physiol Biochem. 2016;40(6):1422-1432. doi: 10.1159/000453194. Epub 2016 Dec 20.
Didymin has been reported to have anti-cancer potential. However, the effect of didymin on liver fibrosis remains illdefined.
Hepatic fibrosis was induced by CCl4 in rats. The effects of didymin on liver pathology and collagen accumulation were observed by hematoxylin-eosin and Masson's trichrome staining, respectively. Serum transaminases activities and collagen-related indicators levels were determined by commercially available kits. Moreover, the effects of didymin on hepatic stellate cell apoptosis and cell cycle were analyzed by flow cytometry. Mitochondrial membrane potential was detected by using rhodamine-123 dye. The expression of Raf kinase inhibitor protein (RKIP) and the phosphorylation of the ERK/MAPK and PI3K/Akt pathways were assessed by Western blot.
Didymin significantly ameliorated chronic liver injury and collagen deposition. It strongly inhibited hepatic stellate cells proliferation, induced apoptosis and caused cell cycle arrest in G2/M phase. Moreover, didymin notably attenuated mitochondrial membrane potential, accompanied by release of cytochrome C. Didymin significantly inhibited the ERK/MAPK and PI3K/Akt pathways. The effects of didymin on the collagen accumulation in rats and on the biological behaviors of hepatic stellate cells were largely abolished by the specific RKIP inhibitor locostatin.
Didymin alleviates hepatic fibrosis by inhibiting ERK/MAPK and PI3K/Akt pathways via regulation of RKIP expression.
据报道，二氢杨梅素具有抗癌潜力。然而，二氢杨梅素对肝纤维化的影响仍不明确。
用四氯化碳诱导大鼠肝纤维化。分别通过苏木精-伊红染色和Masson三色染色观察二氢杨梅素对肝脏病理和胶原沉积的影响。采用市售试剂盒测定血清转氨酶活性和胶原相关指标水平。此外，通过流式细胞术分析二氢杨梅素对肝星状细胞凋亡和细胞周期的影响。用罗丹明-123染料检测线粒体膜电位。通过蛋白质免疫印迹法评估Raf激酶抑制蛋白（RKIP）的表达以及ERK/MAPK和PI3K/Akt信号通路的磷酸化情况。
二氢杨梅素显著改善慢性肝损伤和胶原沉积。它强烈抑制肝星状细胞增殖，诱导凋亡并导致细胞周期停滞于G2/M期。此外，二氢杨梅素显著降低线粒体膜电位，并伴有细胞色素C的释放。二氢杨梅素显著抑制ERK/MAPK和PI3K/Akt信号通路。特异性RKIP抑制剂洛考他汀在很大程度上消除了二氢杨梅素对大鼠胶原沉积和肝星状细胞生物学行为的影响。
二氢杨梅素通过调节RKIP表达抑制ERK/MAPK和PI3K/Akt信号通路来减轻肝纤维化。
