18β-Glycyrrhetinic Acid and a Nano-Liposomal Formulation Alleviate Depression-Like Behaviors via the Microglial mTOR-Autophagy-NLRP3 Axis - PubMed
7 hours ago
- #18β-Glycyrrhetinic acid
- #NLRP3 inflammasome
- #nano-delivery
- 18β-Glycyrrhetinic acid (18β-GA) identified as a potent anti-inflammatory candidate using a zebrafish inflammation-based screening model.
- 18β-GA demonstrated significant antidepressant effects in a chronic social defeat stress (CSDS) mouse model, linked to reduced neuroinflammation and microglial polarization toward an anti-inflammatory phenotype.
- Mechanistically, 18β-GA inhibits the mTOR/p70S6K pathway, restoring autophagy and suppressing NLRP3 inflammasome activation in microglia.
- A transwell co-culture system confirmed 18β-GA protects neurons from microglia-mediated inflammatory injury.
- A nanoliposomal formulation (Nano 18β-GA) was developed to overcome pharmacokinetic limitations, achieving rapid brain accumulation within 0.5 h.
- Single administration of Nano 18β-GA produced significant antidepressant effects, maintained the original mechanism, and showed a favorable biosafety profile.
- The study offers a translational pipeline from natural product discovery to nano-enabled therapy for depressive disorder.