Acori Tatarinowii Rhizoma-Curcumae Radix Herbal pair ameliorates depression by regulating microglia M1/M2 polarization via TLR4/MyD88/NF-κB pathway.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Acori Tatarinowii Rhizoma-Curcumae Radix Herbal pair (ACHP) originating from Changpu Yujin Decoction, which has historically been a traditional prescription for treating depression. Nevertheless, the precise mechanism for ACHP has yet to be fully understood. AIM OF THE STUDY: This study focused on exploring the antidepressant effects of ACHP and elucidate its potential mechanism by combining in silico analysis with multi-pharmacological approaches. MATERIALS AND METHODS: The chemical composition of ACHP was determined by GC/MS and UHPLC-Triple-TOF/MS. ACHP was orally administered to CUMS-induced and depressive-like behaviors in mice for 28 days, and the related biochemical parameters were evaluated. The possible mechanisms were elucidated using qRT-PCR, Western Blot and immunofluorescence, comprehensively. RESULTS: A total of 115 compounds were identified in ACHP. ACHP ameliorated depression symptoms by increasing the preference for sucrose in SPT, reducing the immobility time in TST and FST. Multiple molecular biology techniques analysis indicated the ACHP regulating microglia M1/M2 polarization via TLR4/MyD88/NF-κB pathway both in vivo and in vitro. Moreover, ACHP inhibited neuron apoptosis within a BV2 microglia-N2a neuron interaction model. CONCLUSION: This work demonstrated that ACHP effectively protects against CUMS induced depression-like behaviors, potentially by regulating microglia M1/M2 polarization pathway through the TLR4/MyD88/NF-κB pathway. In conclusion, this study offers new perspectives on the therapeutic possibilities of ACHP in mitigating depressive-like behaviors.