Systems pharmacology and experimental validation of BuYang HuanWu decoction in vertebral artery stenosis: Targeting the AGE-RAGE/NF-κB axis for endothelial protection and plaque stabilization

ETHNOPHARMACOLOGICAL RELEVANCE: BuYang HuanWu Decoction (BYHW), a classical herbal formula first documented in Yilin Gaicuo (1830), is officially listed in the Chinese Pharmacopoeia for the treatment of stroke and sequelae attributed to "qi deficiency and blood stasis." Vertebral artery stenosis (VAS) is a leading cause of posterior circulation ischemic stroke-a condition for which BYHW has been traditionally prescribed. However, the molecular mechanism underlying its therapeutic effects against VAS remains poorly understood. AIM OF THE STUDY: This study aimed to systematically predict the therapeutic targets of BYHW against VAS using network pharmacology and to experimentally validate its core mechanism of action, with a focus on the AGE-RAGE/NF-κB signaling axis. MATERIALS AND METHODS: mice fed a high-fat diet. The standardized aqueous extract (BYHWE) was chemically characterized by HPLC. RESULTS: mice, accompanied by downregulation of p-ERK1/2, p-AKT, and NF-κB p65, and upregulation of β-catenin. CONCLUSIONS: This study provides the first evidence that BYHW alleviates VAS through multi-target modulation of the AGE-RAGE/NF-κB pathway, thereby protecting endothelial function and stabilizing plaques. These findings offer a mechanistic explanation for its traditional use in stroke-related disorders and support its therapeutic potential for atherosclerotic vertebral artery stenosis.