Zhang Junli, Zhang Haiming, Deng Xiaoling, Zhang Ning, Liu Beibei, Xin Shengliang, Li Guixin, Xu Keshu
Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Department of Integrated Traditional Chinese and Western Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China.
Life Sci. 2018 Jan 1;192:46-54. doi: 10.1016/j.lfs.2017.11.027. Epub 2017 Nov 20.
Baicalin (BA), an active flavonoid compound originating from the herb of Scutellaria baicalensis Georgi, has been previously shown to exert anti-inflammation and anti-oxidant effects in liver diseases. However, the potential role of BA in the regulation of non-alcoholic steatohepatitis (NASH) remains elusive. In this study, we newly explored the hepatoprotective effects of BA in MCD diet-induced NASH by ameliorating hepatic steatosis, inflammation, fibrosis and apoptosis.
NASH was induced in mice fed a methionine and choline-deficient (MCD) diet for 4weeks. The mice were simultaneously treated with or without BA for 4weeks. Serum liver functional markers and inflammatory indicators were assessed by biochemical and ELISA methods, respectively. The livers were histologically examined using H&E, Oil Red O and Masson's trichrome staining methods. The qRT-PCR, IHC and Western blotting assays were applied to analyze mechanisms underlying BA protection.
BA treatment significantly attenuated MCD diet-induced hepatic lipid accumulation partly through regulating the expression of SREBP-1c, FASN, PPARα and CPT1a. BA treatment dramatically suppressed MCD diet-induced hepatic inflammation, which was associated with decrease in serum TNF-α, IL-1β and MCP-1 production, macrophage influx and suppression of nuclear factor-κB activation. Additionally, BA was proved to prevent liver fibrosis, which appears to be mediated by inhibition of α-SMA, TGF-β1 and Col1A1. Furthermore, BA markedly inhibited hepatocyte apoptosis and cleaved caspase-3 protein expression in MCD diet-induced mice.
These results provide a possible basis of the underlying mechanism for the application of BA in the treatment of NASH.
黄芩苷（BA）是一种源自黄芩的活性黄酮类化合物，先前已证明其在肝脏疾病中具有抗炎和抗氧化作用。然而，BA在非酒精性脂肪性肝炎（NASH）调控中的潜在作用仍不清楚。在本研究中，我们首次探讨了BA通过改善肝脏脂肪变性、炎症、纤维化和细胞凋亡对蛋氨酸和胆碱缺乏（MCD）饮食诱导的NASH的肝脏保护作用。
给小鼠喂食MCD饮食4周以诱导NASH。小鼠同时接受或不接受BA治疗4周。分别通过生化和ELISA方法评估血清肝功能标志物和炎症指标。使用苏木精-伊红（H&E）、油红O和Masson三色染色方法对肝脏进行组织学检查。应用qRT-PCR、免疫组化（IHC）和蛋白质印迹法分析BA保护作用的潜在机制。
BA治疗部分通过调节固醇调节元件结合蛋白1c（SREBP-1c）、脂肪酸合酶（FASN）、过氧化物酶体增殖物激活受体α（PPARα）和肉碱/有机阳离子转运体1（CPT1a）的表达，显著减轻了MCD饮食诱导的肝脏脂质积累。BA治疗显著抑制了MCD饮食诱导的肝脏炎症，这与血清肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和单核细胞趋化蛋白-1（MCP-1）生成减少、巨噬细胞浸润以及核因子-κB（NF-κB）激活受到抑制有关。此外，BA被证明可预防肝纤维化，这似乎是通过抑制α-平滑肌肌动蛋白（α-SMA）、转化生长因子-β1（TGF-β1）和I型胶原蛋白α1（Col1A1）介导的。此外，BA显著抑制了MCD饮食诱导的小鼠肝细胞凋亡和半胱天冬酶-3（caspase-3）蛋白的裂解表达。
这些结果为BA应用于治疗NASH的潜在机制提供了可能的依据。
