Integrated machine learning and network pharmacology approach for exploring the material basis of Buyang Huanwu Decoction for ischemic stroke

The study investigates the therapeutic effects and mechanisms of Buyang Huanwu Decoction (BHD) in treating ischemic stroke (IS). Using a middle cerebral artery occlusion/reperfusion (MCAO/R) rat model, we evaluated the neuroprotective effects of BHD, demonstrating significant improvements in neurological function scores, prolonged rotarod retention time, and reductions in both infarct volume and brain water content. An unsupervised clustering algorithm was employed to identify active components of BHD by clustering them with FDA-approved drugs for ischemic stroke treatment. Combined with network pharmacology analysis, the mechanisms of these active components were predicted to be associated with anti-inflammatory pathways. Further validation using a lipopolysaccharide (LPS)-induced BV-2 cell model demonstrated the anti-inflammatory efficacy of seven key active components, with their effects on anti-inflammatory activity and cell viability assessed via the Griess and MTT assays. Additionally, the content of these active components in BHD was quantified using liquid chromatography-mass spectrometry (LC-MS). In conclusion, this study elucidates the critical active components of BHD and their potential pharmacological mechanisms, providing valuable insights for the modernization of traditional Chinese medicine and its application in ischemic stroke therapy. All animal experiments were approved by the Animal and Medical Ethics Committee of Northeastern University (approval No.: NEU-EC-2023A052S).