Background: Shengmai San (SMS), a classical traditional Chinese medicine (TCM) formulation, has been clinically used for centuries in the treatment of ischemic stroke (IS). However, the complexity of SMS leads to ambiguous bioactive components and poorly understood mechanisms of action. Therefore, the development of optimized active component combinations from SMS represents a promising strategy for novel therapeutic agents against IS. Methods: In this study, we developed an active component combination (ACCS) from SMS and evaluated the neuroprotective effect of ACCS in a rat middle cerebral artery occlusion (MCAO) model. An integrated multi-omics approach, combining 16S rRNA gut microbiota sequencing with serum untargeted metabolomics, was employed to elucidate the underlying neuroprotective mechanisms. Results: ACCS treatment significantly reduced cerebral infarct volume, improved neurobehavioral function, and restored cerebral blood flow in the ischemic region. Furthermore, ACCS modulated gut microbial structure, restored microbial diversity and increased the abundance of beneficial bacterial populations. Meanwhile, ACCS ameliorated serum metabolic disturbances induced by MCAO. Conclusion: This study rationally designed a bioactive combination derived from a TCM formulae, establishing a polypharmacological strategy for the treatment of ischemic stroke.
Li et al. (2026) studied this question.