Ding Mingning, Zhou Fei, Li Yijie, Liu Chuanyang, Gu Yiqing, Wu Jianzhi, Fan Guifang, Li Yajing, Li Xiaojiaoyang
School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China.
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
Chin Herb Med. 2023 Mar 22;15(3):421-429. doi: 10.1016/j.chmed.2022.09.006. eCollection 2023 Jul.
(CS, Juemingzi in Chinese) has been used for thousands of years in ancient Chinese history for relieving constipation, improving liver function as well as preventing myopia. Here we aimed to elucidate the anti-steatosis effect and underlying mechanism of CS against non-alcoholic fatty liver disease (NAFLD).
High-performance liquid chromatography (HPLC) was used to identify the major components of CS water extract. Mice were fed with a high-fat and sugar-water (HFSW) diet to induce hepatic steatosis and then treated with CS. The anti-NAFLD effect was determined by measuring serum biomarkers and histopathology staining. Additionally, the effects of CS on cell viability and lipid metabolism in oleic acid and palmitic acid (OAPA)-treated HepG2 cells were measured. The expression of essential genes and proteins involved in lipid metabolism and autophagy signalings were measured to uncover the underlying mechanism.
Five compounds, including aurantio-obtusin, rubrofusarin gentiobioside, cassiaside C, emodin and rhein were simultaneously identified in CS extract. CS not only improved the diet-induced hepatic steatosis , as indicated by decreased number and size of lipid droplets, hepatic and serum triglycerides (TG) levels, but also markedly attenuated the OAPA-induced lipid accumulation in hepatocytes. These lipid-lowering effects induced by CS were largely dependent on the inhibition of fatty acid synthase (FASN) and the activation of autophagy-related signaling, including AMP-activated protein kinase (AMPK), light chain 3-II (LC3-II)/ LC3-1 and autophagy-related gene5 (ATG5).
Our study suggested that CS effectively protected liver steatosis via decreasing FASN-related fatty acid synthesis and activating AMPK-mediated autophagy, which might become a promising therapeutic strategy for relieving NAFLD.
决明子在中国古代历史中已被使用数千年，用于缓解便秘、改善肝功能以及预防近视。在此，我们旨在阐明决明子对非酒精性脂肪性肝病（NAFLD）的抗脂肪变性作用及其潜在机制。
采用高效液相色谱法（HPLC）鉴定决明子水提取物的主要成分。给小鼠喂食高脂高糖饮食（HFSW）以诱导肝脂肪变性，然后用决明子进行治疗。通过测量血清生物标志物和组织病理学染色来确定其抗NAFLD作用。此外，还测量了决明子对油酸和棕榈酸（OAPA）处理的HepG2细胞的细胞活力和脂质代谢的影响。测量参与脂质代谢和自噬信号传导的关键基因和蛋白质的表达，以揭示潜在机制。
在决明子提取物中同时鉴定出5种化合物，包括橙黄决明素、红镰霉素龙胆二糖苷、决明子苷C、大黄素和大黄酸。决明子不仅改善了饮食诱导的肝脂肪变性，表现为脂滴数量和大小减少、肝脏和血清甘油三酯（TG）水平降低，还显著减轻了OAPA诱导的肝细胞脂质积累。决明子诱导的这些降脂作用在很大程度上依赖于对脂肪酸合酶（FASN）的抑制以及自噬相关信号的激活，包括AMP活化蛋白激酶（AMPK）、轻链3-II（LC3-II）/LC3-I和自噬相关基因5（ATG5）。
我们的研究表明，决明子通过减少FASN相关的脂肪酸合成和激活AMPK介导的自噬，有效保护肝脏脂肪变性，这可能成为缓解NAFLD的一种有前景的治疗策略。
