Mechanistic insights into the neuroprotective effects of yangyin formula on cerebral ischemia-reperfusion injury via the IL-17A/MAPK/NF-κB signaling pathway.

Ischemic stroke is a leading cerebrovascular disorder frequently complicated by cerebral ischemia-reperfusion injury (CIRI), which aggravates neurological damage and worsens clinical outcomes. Yangyin Formula (YYF), a traditional Chinese medicine composed of Rehmannia glutinosa, Dendrobium officinale, and Pueraria lobata, has shown potential in mitigating CIRI. To elucidate its therapeutic mechanisms, we integrated network pharmacology, molecular docking, and molecular dynamics simulations, followed by in vivo validation in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). A total of 61 bioactive compounds and 768 targets were identified, enriched in 136 signaling pathways. Computational analyses revealed strong binding affinities between key YYF components and CIRI-related targets. In vivo, YYF administration significantly improved neurological function, reduced infarct volume, and alleviated histopathological damage. Furthermore, YYF suppressed IL-17A, TNF-α, IL-1β, Caspase-3, p38 MAPK, and NF-κB p65 expression in brain and serum, with effects comparable to IL-17A inhibition. These findings suggest that YYF exerts neuroprotective effects against CIRI by modulating the IL-17A/p38 MAPK/NF-κB p65 signaling pathway, highlighting its potential as a therapeutic strategy for ischemic stroke.