Systematic Analysis to Explore the Multiple Bioactive Ingredients and Mechanisms of <i>Bupleurum Chinense</i> DC. for Treating Neurodegenerative Diseases

Abstract Bupleurum chinense DC., a traditional Chinese medicinal herb, has been historically valued for its roots, while its aerial parts remain understudied. Emerging evidence highlights the abundance of flavonoids in these underutilized aerial segments, which exhibit significant therapeutic potential against neurodegenerative pathologies. This study employed network pharmacology to explore the bioactive constituents and mechanisms underlying the neuroprotective effects of B. chinense aerial parts. Major compounds identified, include β ‐Sitosterol (10), Kaempferol‐7‐ O ‐ α ‐ l ‐rhamnoside (23), linarin (7), Isorhamnetin‐7‐ O ‐ α ‐ l ‐rhamnoside (18), and luteolin (24), demonstrating strong binding affinities to critical targets, such as acetylcholinesterase (4M0F), glutamate carboxypeptidase 2 (2C6C), and nitric oxide synthase 1 (4NOS). GO and KEGG pathway analyses revealed that these compounds might exert neuroprotective effects through calcium signaling pathway (hsa04020), cAMP signaling pathway (hsa04024), Alzheimer's disease (hsa05010), and HIF‐1 signaling pathway (hsa04066). Experimental validation confirmed potent AChE inhibitory activity, and neuroprotective assays confirmed a similar protective effect against H 2 O 2 ‐induced injury in SH‐SY5Y cells. Additionally, electronic analyzes were performed using the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) to gain insights into the chemical reactivity and stability of these compounds. These findings highlight the therapeutic promise of B. chinense aerial parts as multi‐target agents for neurodegenerative disorders.