How ginseng regulates autophagy: Insights from multistep process

Although autophagy is a recognized contributor to the pathogenesis of human diseases, chloroquine and hydroxychloroquine are the only two FDA-approved autophagy inhibitors to date. Emerging evidence has revealed the potential therapeutic benefits of various extracts and active compounds isolated from ginseng, especially ginsenosides and their derivatives, by mediating autophagy. Mechanistically, active components from ginseng mediate key regulators in the multistep processes of autophagy, namely, initiation, autophagosome biogenesis and cargo degradation.

To date, a review that systematically described the relationship between ginseng and autophagy is still lacking. Breakthroughs in finding the key players in ginseng-autophagy regulation will be a promising research area, and will provide positive insights into the development of new drugs based on ginseng and autophagy.

Here, we comprehensively summarized the critical roles of ginseng-regulated autophagy in treating diseases, including cancers, neurological disorders, cardiovascular diseases, inflammation, and neurotoxicity. The dual effects of the autophagy response in certain diseases are worthy of note; thus, we highlight the complex impacts of both ginseng-induced and ginseng-inhibited autophagy. Moreover, autophagy and apoptosis are controlled by multiple common upstream signals, cross-regulate each other and affect certain diseases, especially cancers. Therefore, this review also discusses the cross-signal transduction pathways underlying the molecular mechanisms and interaction between ginseng-regulated autophagy and apoptosis.