Screening Key Compound in Ligusticum chuanxiong Hort. for Anti-Parkinson's Disease Based on an Experimental and Computational Framework.

Ligusticum chuanxiong Hort. (CX), a traditional herbal plant, has demonstrated significant therapeutic potential for treating neurological disorders. However, systematic studies screening its key active compounds for Parkinson's disease (PD) have been limited. This study aims to comprehensively identify the primary anti-PD compounds derived from CX by integrating computational and experimental approaches, including network pharmacology, HPLC analysis, spectrum-effect relationships, and molecular docking, alongside cellular and animal model validation. Our findings indicate that among the three CX extracts tested, CXEO (essential oil of CX) exhibited the most potent anti-PD activity. Spectrum-effect relationship analysis, validated through experimental studies, identified Senkyunolide A as the key active compound in CXEO. Network pharmacology analysis, further supported by validation using the GEO database, revealed tumor necrosis factor (TNF), interleukin 1β (IL-1β), intercellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule-1 (VCAM1), and prostaglandin endoperoxide synthase 2 (PTGS2) as the primary molecular targets through which Senkyunolide A exerts its anti-PD effects, suggesting that its mechanism of action may involve modulation of inflammatory pathways. Additional investigation into differentially expressed genes related to PD, based on the GEO database, further confirmed the clinical relevance of Senkyunolide A in PD. These findings suggest that Senkyunolide A from L. chuanxiong Hort. holds potential as a therapeutic compound for PD.