Meng Wenya, Zhao Zitong, Chen Lingli, Lin Suyun, Zhang Yang, He Jing, Ouyang Kehui, Wang Wenjun
Jiangxi Key Laboratory of Natural Products and Functional Food, College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang 330045, China.
College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China.
Foods. 2022 Jul 21;11(14):2169. doi: 10.3390/foods11142169.
Non-alcoholic fatty liver disease (NAFLD) is one of the chronic liver diseases with high incidence in the world. This study aimed to investigate whether total flavonoids from Oliv. leaves (TFC) can ameliorate NAFLD. Herein, a high-fat diet (HFD)-induced NAFLD mice model was established, and TFC was administered orally. The results showed that TFC reduced the body weight and liver index and decreased the serum and hepatic levels of triglyceride (TG) and total cholesterol (TC). TFC significantly reduced the activity of liver functional transaminase. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) decreased by 34.61% and 39.57% in serum and 22.46% and 40.86% in the liver, respectively. TFC regulated the activities of oxidative-stress-related enzymes and upregulated the protein expression of nuclear factor E2-related factor (Nrf2)/heme oxygenase (HO-1) pathway in NAFLD mice, and the activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX) in serum were increased by 89.76% and 141.77%, respectively. In addition, TFC reduced the levels of free fatty acids (FFA), endotoxin (ET), and related inflammatory factors in mouse liver tissue and downregulated the expression of proteins associated with inflammatory pathways. After TFC treatment, the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1β in the liver tissues of NAFLD mice were downregulated by 67.10%, 66.56%, and 61.45%, respectively. Finally, TFC reduced liver fat deposition, oxidative stress, and inflammatory response to repair liver damage and alleviate NAFLD. Further studies showed that TFC regulated the expression of intestinal-barrier-related genes and improved the composition of gut microbiota. Therefore, TFC reduced liver inflammation and restored intestinal homeostasis by regulating the gut-liver axis. Overall, our findings revealed a novel function of TFC as a promising prophylactic for the treatment of NAFLD.
非酒精性脂肪性肝病(NAFLD)是全球发病率较高的慢性肝病之一。本研究旨在探讨油橄榄叶总黄酮(TFC)是否能改善NAFLD。在此,建立了高脂饮食(HFD)诱导的NAFLD小鼠模型,并口服给予TFC。结果显示,TFC降低了体重和肝脏指数,降低了血清和肝脏中甘油三酯(TG)和总胆固醇(TC)的水平。TFC显著降低了肝功能转氨酶的活性。血清中天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)分别降低了34.61%和39.57%,肝脏中分别降低了22.46%和40.86%。TFC调节了氧化应激相关酶的活性,并上调了NAFLD小鼠中核因子E2相关因子(Nrf2)/血红素加氧酶(HO-1)途径的蛋白表达,血清中总超氧化物歧化酶(T-SOD)和谷胱甘肽过氧化物酶(GSH-PX)的活性分别增加了89.76%和141.77%。此外,TFC降低了小鼠肝脏组织中游离脂肪酸(FFA)、内毒素(ET)和相关炎症因子的水平,并下调了与炎症途径相关的蛋白表达。TFC处理后,NAFLD小鼠肝脏组织中肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6和IL-1β的水平分别下调了67.10%、66.56%和61.45%。最后,TFC减少了肝脏脂肪沉积、氧化应激和炎症反应,以修复肝脏损伤并减轻NAFLD。进一步研究表明,TFC调节了肠道屏障相关基因的表达,并改善了肠道微生物群的组成。因此,TFC通过调节肠-肝轴减少肝脏炎症并恢复肠道稳态。总体而言,我们的研究结果揭示了TFC作为一种有前景的预防NAFLD治疗药物的新功能。