Asiaticoside attenuates renal fibrosis by targeting STAT3 to restore Th17/Treg homeostasis - PubMed
4 hours ago
- #STAT3
- #renal-fibrosis
- #Th17-Treg-homeostasis
- Asiaticoside (AS) attenuates renal fibrosis by targeting STAT3 to restore Th17/Treg homeostasis.
- AS exhibits anti-inflammatory and antifibrotic activities, with STAT3 identified as the core target through network pharmacology.
- Treatment with AS in UUO mice significantly reduced renal fibrosis, improved renal function, and rebalanced Th17/Treg ratios.
- AS directly binds to the STAT3 SH2 domain, inducing conformational destabilization and suppressing STAT3 activation.
- Molecular docking and dynamics simulations revealed a 'local anchoring-allosteric effect' mode within the STAT3 SH2 domain.
- AS inhibits IL-17A and total STAT3 mRNA expression, reducing STAT3 and p-STAT3 levels in renal tissues.
- STAT3 inhibitor Stattic mimicked AS's effects, while agonist Colivelin exacerbated fibrosis, partially rescued by AS.
- AS alleviates renal fibrosis via a novel 'bind to destabilize' mechanism, offering a new therapeutic strategy for STAT3-driven fibrotic diseases.