Asiatic Acid Attenuates-Induced Neuroinflammation and Neuronal Damage by Inhibiting the TLR2/Notch and NF-κB Pathway in Microglia.

Abstract

() infection of the central nervous system (CNS) induces severe inflammation, leading to elevated expression of inducible nitric oxide synthase (iNOS) in microglia. This process catalyzes excessive production of nitric oxide (NO), resulting in irreversible damage to neuronal mitochondria. Asiatic acid (AA) is a small molecule with neuroprotective potential; however, its ability to counteract nerve injury induced byand the underlying mechanisms remain unclear. In this study, we established an-infected mouse model (in vivo) and an-stimulated microglial model using BV-2 cells (in vitro) and employed techniques including immunofluorescence (IF), Western blot, co-immunoprecipitation (Co-IP), and RNA extraction and quantitative reverse transcription PCR (RT-qPCR) to systematically evaluate the protective effects and mechanisms of AA. The results showed that pre-treatment with AA significantly reduced the expression of iNOS and the production of NO caused byinfection in mouse hippocampal tissue and BV-2 cells. Mechanistically, AA exerts its effects by inhibiting the upstream Toll-like receptor 2 (TLR2)/Notch and nuclear factor-κB (NF-κB) signaling axis. It interferes with the nuclear translocation of Notch and p65 proteins and their complex formation understimulation, thereby blocking downstream expression of iNOS and production of NO. This study reveals a novel mechanism by which AA alleviates infection-related neuroinflammation through targeting Notch-p65 interactions, providing a new theoretical basis for its clinical application.