Pandanus Amaryllifolius Roxb. Polyphenol Extract Alleviates NAFLD via Regulating Gut Microbiota and AMPK/AKT/mTOR Signaling Pathway

With the drastic changes in lifestyle, nonalcoholic fatty liver disease (NAFLD) has become a widespread health problem. Natural actives such as polyphenols have multi-target, multi-mechanism characteristics, and offer new opportunities for NAFLD treatment. This study established a high-fat diet (HFD)-induced NAFLD model in mice to investigate the molecular mechanism of <i>Pandanus amaryllifolius Roxb.</i> polyphenol extract (PAE) in alleviating NAFLD. The results showed that PAE significantly inhibited HFD-induced obesity, maintained glucose homeostasis, mitigated oxidative damage in liver tissue, and reduced liver steatosis. Moreover, PAE treatment remarkably reversed 16 endogenous DMs, and significantly affected glycerophospholipid metabolism, which increased the levels of phosphatidylcholine and phosphatidylethanolamine, and down-regulated choline and sn-glyceropl-3P. Further validation revealed that PAE was able to prevent NAFLD progression by regulating the AMPK/AKT/mTOR signaling pathway to enhance autophagy levels. Meanwhile, PAE treatment restored the balance of gut microbiota mainly by increasing the relative abundance of <i>Bacteroidetes</i>, decreasing the relative abundance of <i>Firmicutes</i> and the ratio of <i>Firmicutes</i>/<i>Bacteroidetes</i>. Overall, the findings highlight that the mechanism by which PAE alleviates NAFLD may be related to the regulation of the gut microbes and AMPK/AKT/mTOR signaling pathway, enriching the health-promoting effects of PAE on NAFLD.