EWM-CRITIC-VIKOR framework reveals mechanistic insights of Buyang Huanwu Decoction in ischemic stroke with experimental validation

Buyang Huanwu Decoction (BYHWD), a classical formula recorded in Yilin Gaicuo, has been widely used for the treatment of stroke and post-stroke sequelae in traditional Chinese medicine.

This study aims to establish a novel framework based on the EWMCRITIC-VIKOR algorithm to prioritize potential BYHWD targets against IS by integrating multi-dimensional biological features, with validation through in vivo experiments.

14 biological features across 4 dimensions were quantified. Feature weights were calculated using EWM and CRITIC, and integrated via VIKOR for MCDM on BYHWD-IS overlapping targets. The therapeutic effects of BYHWD were validated in middle cerebral artery occlusion (MCAO) rat model. Anti-inflammatory effects were assessed by RT-qPCR and ELISA, while western blotting were used to evaluate signaling via the PI3K/AKT/NF-κB pathway.

The EWM-CRITIC-VIKOR framework prioritized 5 key targets (FOS, IL1β, AKT1, TP53, and IL6) from 239 overlapping targets. The VIKOR compromise solution exhibited a distinct low-Q priority set, in which the top targets jointly minimized group utility and individual regret, and the overall ranking showed weak association with logFC, indicating that prioritization was not driven by expression effect size alone. BYHWD treatment significantly improved MCAO-induced brain injury. RT-qPCR and ELISA showed marked downregulation of IL1B and IL6 after BYHWD treatment, and western blotting indicated altered PI3K/AKT/NF-κB signaling status.

The EWM-CRITIC-VIKOR framework enables robust prioritization of therapeutic targets by integrating heterogeneous biological data. This approach enhances mechanistic understanding of BYHWD in IS and offers a reliable strategy for target discovery in herbal interventions.