Liu Huiru, Meng Wenwen, Zhao Dongsheng, Ma Zhihui, Zhang Wenguang, Chen Zhi, Li Zhengguo, Zhao Pan
College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
Jining Food and Drug Inspection and Testing Research Institute, Jining, Shandong, China.
Front Pharmacol. 2023 Jan 11;13:1074286. doi: 10.3389/fphar.2022.1074286. eCollection 2022.
The objective of this study was to investigate the effects and molecular mechanisms of total flavonoids from Cortex Juglandis Mandshuricae (TFC) on preventing alcohol-induced chronic liver injury and regulating gut microbiota in mice. The results showed that oral administration of TFC significantly attenuated alcoholic liver injury in mice. TFC improved lipid accumulation in mice with chronic alcoholic liver injury through activation of the AMPK/PPARα pathway. In addition, TFC maintained the integrity of the intestinal barrier in alcoholic mice, reducing endotoxin leakage from the intestine and further inhibiting the TLR4/NF-κB inflammatory pathway. More importantly, TFC regulated the intestinal microbiota composition and certain bacteria, including and others. At the same time, reduced levels of short-chain fatty acids due to alcohol consumption were restored. In summary, TFC upregulated AMPK/PPARα signaling pathway to improve hepatic fat accumulation and oxidative stress; TFC positively regulated intestinal flora composition to reduce intestinal disorders caused by alcohol consumption, and further inhibited alcohol-induced inflammatory responses through the intestinal-liver axis. The above findings may be the mechanism of TFC's pharmacological effects against alcoholic liver injury.
本研究旨在探讨核桃楸皮总黄酮（TFC）对预防小鼠酒精性慢性肝损伤及调节肠道微生物群的作用和分子机制。结果表明，口服TFC可显著减轻小鼠酒精性肝损伤。TFC通过激活AMPK/PPARα途径改善慢性酒精性肝损伤小鼠的脂质蓄积。此外，TFC维持酒精性小鼠肠道屏障的完整性，减少肠道内毒素泄漏，并进一步抑制TLR4/NF-κB炎症途径。更重要的是，TFC调节肠道微生物群组成及某些细菌，包括[具体细菌名称缺失]等。同时，恢复了因饮酒导致的短链脂肪酸水平降低。综上所述，TFC上调AMPK/PPARα信号通路以改善肝脏脂肪蓄积和氧化应激；TFC正向调节肠道菌群组成以减少饮酒引起的肠道紊乱，并通过肠-肝轴进一步抑制酒精诱导的炎症反应。上述发现可能是TFC对酒精性肝损伤药理作用的机制。
