Synergistic Modulation of Microglial Polarization by Acteoside and Ferulic Acid via Dual Targeting of Nrf2 and RORγt to Alleviate Depression-Associated Neuroinflammation.

ABSTRACT: Acteoside (ACT) and ferulic acid (FA), the principal bioactive constituents of Baihe Dihuang decoction (BDD), possess established anti-inflammatory and antidepressant properties, but their combined effect on microglial phenotype modulation remains unclear. Integrated multi-source data and machine learning identified ACT and FA as BDD's core components, mediating therapeutic effects via neurotransmitter regulation and inflammatory suppression. Co-administering ACT and FA at their BDD ratio replicated the parent formulation's anti-inflammatory and antidepressant effects. Both compounds stabilized Nrf2, with ACT exhibiting greater potency. Crucially, the ACT/FA combination shifted microglia from pro-inflammatory M1 to neuroprotective M2 phenotypes via dual activation of Nrf2 and RORγt pathway

SUBMITTER: Guo D 

PROVIDER: S-EPMC12631924 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature