A network pharmacological target mendelian randomization study on the neuroprotective effects of active ingredients in mahuang fuzi xixin decoction for multiple sclerosis

Mahuang Fuzi Xixin Decoction (MFX), a traditional Chinese medicine containing 44 volatile components (97.36% total oil), includes key compounds like α-terpenol (13.34%) and 1,2,3-trimethoxy-5-methyl-benzene (22.64%). Using network pharmacology and Mendelian randomization, 24 active compounds were identified targeting MS-related pathways (NF-κB, NLRP3, Toll-like receptor). Genetic variants in CYP450, GSK3B, CYBB, and PON1 correlated with reduced MS risk. In EAE mice, MFX decreased spinal GSK-3B expression (immunofluorescence) and pro-inflammatory factors (ELISA), demonstrating neuroprotection via anti-inflammatory, antioxidative mechanisms and restored GSK-3B levels, highlighting therapeutic potential for MS.