Unlocking the Therapeutic Potential of Autophagy Modulation by Natural Products in Tackling Non‐Alcoholic Fatty Liver Disease

It is widely recognized that there is currently no established treatment for individuals with Non-alcoholic Fatty Liver Disease (NAFLD). In recent years, there has been a surge of interest in natural products derived from plants, driven by their minimal toxicity and notable efficacy. It was reported that natural products could ameliorate NAFLD via various mechanisms. On the other hand, autophagy has been suggested to be involved in the pathogenesis of NAFLD. The aim of this review is to understand whether the beneficial effects of natural products on NAFLD are mediated by affecting autophagy pathways. In this review, we have compiled data elucidating how these natural products exhibit the potential to improve NAFLD by modulating core autophagic pathways. Specifically, we demonstrate that these natural products, including resveratrol, berberine, curcumin, quercetin, punicalagin, epigallocatechin-3-gallate, apigenin, and many others, regulate autophagy through key signaling pathways, such as AMPK/SIRT1/mTOR. Interestingly, these compounds might activate or inhibit autophagy, depending on the context. We explore how autophagy activation promotes the degradation of lipid droplets and alleviates liver injury, while autophagy inhibition contributes to reducing inflammation, apoptosis, and pyroptosis, and also resulting in improved NAFLD outcomes. Taken together, these findings suggest that targeting autophagy with natural products presents a promising mechanism for preventing and treating NAFLD.