Chuanxiong-Renshen medicine pair ameliorates neuroinflammation in Alzheimer’s disease through modulation of the PKC-α/NF-κB signaling pathway

BACKGROUND AND AIM: Previous studies have identified Chuanxiong Renshen decoction as a promising anti-Alzheimer's disease (AD) agent, with its brain-penetrating components characterized via UHPLC-MS/MS. This study further elucidates the anti-neuroinflammatory mechanisms of Chuanxiong-Renshen medicine pair (CRM) in AD. MATERIALS AND METHODS: expression (flow cytometry), pro-inflammatory cytokines, and PKC-α/NF-κB pathway proteins. Pathway specificity was further validated using the PKC-α inhibitor Gö6976. RESULTS: , P-Tau, and APP expression in 3 × Tg-AD mice. Mechanistically, CRM suppressed PKC-α/NF-κB signaling, down-regulating iNOS, COX-2, and p-NF-κB p65 in microglia, with synergistic effects observed upon PKC-α inhibition. Additionally, CRM modulated gut microbiota composition, notably reducing Proteobacteria abundance, which correlated with hippocampal Iba-1 and APP levels. CONCLUSION: These findings demonstrate that CRM exerts neuroprotective effects in AD through dual mechanisms: inhibition of PKC-α/NF-κB-mediated neuroinflammation and restoration of gut microbiota homeostasis. Thus, CRM represents a promising multi-target therapeutic strategy for AD.