Dehydrocorydaline in Corydalis Yanhusuo Promotes M2 Microglial Polarization and Alleviates Neuroinflammation After Cerebral Ischemia‐Reperfusion Injury by Inhibiting the JAK1/STAT3 Pathway

Ischemic stroke is the third leading cause of death and disability worldwide. Cerebral ischemia-reperfusion injury leads to severe neuroinflammation, in which microglial polarization plays a key role. Dehydrocorydaline (DHC), the main alkaloid of Corydalis yanhusuo, has anti-inflammatory and neuroprotective effects. However, it is unknown if it controls microglial polarization to lessen cerebral ischemia-reperfusion injury. A mouse middle cerebral artery occlusion (MCAO) model and an in vitro microglial oxygen-glucose deprivation/reoxygenation (OGD/R) model were used. 2,3,5-triphenyltetrazolium chloride (TTC) staining, neurological function scores, flow cytometry, Enzyme-Linked Immunosorbent Assay, and Western blot were used to evaluate the efficacy and mechanism of DHC. A rescue experiment was also conducted using the Janus Kinase 1 (JAK1) agonist coumermycin A1 (CMA1). Compared with the MCAO group, DHC treatment significantly reduced cerebral infarction volume and significantly improved neurological function scores, motor coordination, and sensorimotor function. DHC effectively reduced hippocampal neuronal damage. At the same time, DHC treatment significantly decreased the level of pro-inflammatory factors in brain tissue, while increasing the level of anti-inflammatory factors. DHC significantly reduced the expression of M1 phenotype markers and upregulated the expression of M2 phenotype markers. Mechanistically, DHC significantly inhibited the phosphorylation levels of JAK1 and Signal Transducer and Activator of Transcription 3 (STAT3), while the JAK1 agonist CMA1 completely reversed the above-mentioned protective effects of DHC. DHC reduces neuroinflammation and has a neuroprotective impact against cerebral ischemia-reperfusion injury by blocking the JAK1/STAT3 signaling pathway and encouraging microglia to polarize to the M2 phenotype.