Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, 33302 Taoyuan City, Taiwan.
Graduate Institute of Traditional Chinese Medicine, School of Chinese Medicine, College of Medicine, Chang Gung University, 33302 Taoyuan City, Taiwan.
Front Biosci (Landmark Ed). 2022 Aug 15;27(8):242. doi: 10.31083/j.fbl2708242.
Non-alcoholic fatty liver disease (NAFLD) has become a prevalent issue and a consequence of metabolic syndrome impact on human health. Both of anti-atherosclerosis and anti-hepatic fibrosis capabilities of herbal medicine Ger-Gen-Chyn-Lian-Tang (GGCLT) has attracted attention, but their molecular regulatory mechanisms in a NAFLD model have not been elucidated. The aim of the present study was to explore the bioactivity of mice following treatment with GGCLT.
NAFLD phenotype of mice were treated with GGCLT and lipogenesis, mitochondria dysfunction, mitophagy, macrophage polarization and adipose tissue browning were then evaluated using qRT-PCR and/or Western blot analysis, immunofluorescence, and immunohistochemistry assays, respectively.
GGCLT not only decreased serum levels of TG and free fatty acids, but glucose and insulin tolerance test in mice. In parallel, GGCLT reduced lipogenesis and hypoxia-inflammation cascades in NAFLD progression. GGCLT reduced lipid accumulation and was accompanied by the enhanced mitochondria biogenesis, M2 macrophage, and decreased M1 macrophage. The latter two events contributing to the anti-inflammation are resulting from mitochondria dynamics, and the lipotoxicity lowering effect of GGCLT of NAFLD mice is mediated by promoting mitophagy in Parkin-dependent and -independent pathways, by mitochondrial fusion over fission manner. GGCLT also inactivated lipogenesis and decreased lipid accumulation in epididymal white adipose tissue with a higher M2/M1 macrophage ratio.
Besides in the liver, modulating of mitochondrial biogenesis and adipose tissue browning were characterized by increased , , and expression by GGCLT in EWAT also contributes to the beneficial action in NAFLD.
非酒精性脂肪性肝病（NAFLD）已成为代谢综合征对人类健康影响的一个普遍问题和后果。草药葛芪连汤（GGCLT）的抗动脉粥样硬化和抗肝纤维化能力引起了人们的关注，但它们在 NAFLD 模型中的分子调节机制尚未阐明。本研究旨在探讨 GGCLT 处理后小鼠的生物活性。
用 GGCLT 处理 NAFLD 表型小鼠，然后用 qRT-PCR 和/或 Western blot 分析、免疫荧光和免疫组织化学检测分别评估脂肪生成、线粒体功能障碍、线粒体自噬、巨噬细胞极化和脂肪组织棕色化。
GGCLT 不仅降低了 小鼠血清中 TG 和游离脂肪酸的水平，还降低了血糖和胰岛素耐量试验。与此同时，GGCLT 减少了 NAFLD 进展中的脂肪生成和缺氧-炎症级联反应。GGCLT 减少了脂质积累，并伴随着线粒体生物发生、M2 巨噬细胞的增强和 M1 巨噬细胞的减少。后两个事件有助于抗炎，这是由于线粒体动力学，而 GGCLT 降低 NAFLD 小鼠的脂毒性作用是通过促进 Parkin 依赖和非依赖途径的线粒体自噬来介导的，通过线粒体融合超过分裂的方式。GGCLT 还在附睾白色脂肪组织中抑制脂肪生成并减少脂质积累，同时具有更高的 M2/M1 巨噬细胞比值。
除了在肝脏中，线粒体生物发生和脂肪组织棕色化的调节通过 GGCLT 在 EWAT 中增加 、 和 的表达也有助于 NAFLD 的有益作用。
