Sun Chunbin, Zhang Jin, Hou Jiong, Hui Menglin, Qi Hualong, Lei Tong, Zhang Xiaoshuang, Zhao Luxi, Du Hongwu
School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, China.
Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
Biomed Pharmacother. 2023 Jan;157:114005. doi: 10.1016/j.biopha.2022.114005. Epub 2022 Nov 13.
Non-alcoholic fatty liver disease (NAFLD) is the most common among lipid metabolism disorders. Autophagy plays an important role in lipid metabolism in NAFLD. Pueraria flavonoids, the main active ingredients of Pueraria lobata, exert antioxidant and anti-inflammatory effects. Herein, we report the potential lipid-lowering and anti-inflammatory effects of Pueraria flavonoids on NAFLD induced by a high-fat diet. In vivo and in vitro experiments showed that Pueraria flavonoids reduced intracellular lipid deposition by inhibiting lipid synthesis and the release of pro-inflammatory cytokines. We analyzed the autophagy flux by mRFP-GFP-LC3 plasmid transfection to assess the role of autophagy in intracellular scavenging. After treating mice fed on high fat and HepG2 cells with Pueraria flavonoids, the number of autophagosomes increased significantly, along with the level of autophagy. The autophagy loss after siRNA transfection aggravated lipid deposition and the release of inflammatory cytokines. Mechanistically, Pueraria flavonoids trigger autophagy through PI3K/Akt/mTOR signaling pathway to reduce lipid deposition and inflammation. In summary, our results showed that Pueraria flavonoids stimulated autophagy by inhibiting the PI3K/Akt/mTOR signaling pathway, thereby reducing intracellular lipid accumulation and inflammation levels and alleviating NAFLD.
非酒精性脂肪性肝病（NAFLD）是脂质代谢紊乱中最常见的疾病。自噬在NAFLD的脂质代谢中起重要作用。葛根黄酮是葛根的主要活性成分，具有抗氧化和抗炎作用。在此，我们报道了葛根黄酮对高脂饮食诱导的NAFLD的潜在降脂和抗炎作用。体内和体外实验表明，葛根黄酮通过抑制脂质合成和促炎细胞因子的释放来减少细胞内脂质沉积。我们通过mRFP-GFP-LC3质粒转染分析自噬通量，以评估自噬在细胞内清除中的作用。用葛根黄酮处理高脂喂养的小鼠和HepG2细胞后，自噬体数量显著增加，同时自噬水平也升高。siRNA转染后自噬缺失加剧了脂质沉积和炎性细胞因子的释放。机制上，葛根黄酮通过PI3K/Akt/mTOR信号通路触发自噬，以减少脂质沉积和炎症。总之，我们的结果表明，葛根黄酮通过抑制PI3K/Akt/mTOR信号通路刺激自噬，从而减少细胞内脂质积累和炎症水平，减轻NAFLD。
