Plant derived modulators of autophagy in infectious disease, mechanisms and therapeutic potential

Autophagy is an evolutionarily conserved intracellular degradation pathway that ensures cellular homeostasis and contributes to host defence against infectious pathogens. An increasing body of evidence demonstrates that natural products (such as polyphenols, flavonoids, terpenoids, alkaloids and polysaccharides) derived from plants modulate autophagy through major molecular hubs, including the AMPK–mTOR–ULK1 axis, the Beclin-1–Vps34 complex and ROS-involving JNK stress-response pathways. These interactions can enable phytochemicals to promote xenophagy-mediated clearance of viruses, bacteria and at the same time attenuate infection-associated inflammation, oxidative stress and tissue damage. Certain compounds (including curcumin, resveratrol, EGCG, berberine quercetin and artemisinin) have shown remarkable autophagy-dependent antimicrobial action in vitro and vivo; additionally growing data indicated that it suggests synergistic effect when accompanying the classical antimicrobials molecules. Although challenges associated with bioavailability, dose-dependent autophagy modulation and herbal-drug interactions exist, these compounds are a valuable source of new host-directed therapeutics. The latter review offers a pathway-centric summary of natural products that modulate autophagy against viral, bacterial and fungal infections, correlating the activity of specific phytochemicals with AMPK–mTOR–ULK1, Beclin-1-Vps34 and ROS–JNK-mediated signalling and xenophagy. In particular, it accentuates antimicrobial synergy, translational inhibition potential, and host-directed therapeutic potential for a holistic perspective on the unexplored ‘Phyto-pharmacology of autophagy’ targeted modulation.