Dehydrocorybulbine blocks the Lyn-mediated MAPK pathway to promote anti-inflammatory polarization of microglia in mice after sevoflurane anesthesia

Dehydrocorybulbine (DHCB) has demonstrated efficacy in alleviating thermally induced acute pain. The present study sought to study the impact of DHCB on postoperative cognitive dysfunction (POCD). Mice or mouse BV2 cells were exposed to sevoflurane for modeling. Behavioral tests (Morris water maze, Y-maze, and novel object recognition test) and western blot analysis of APP, p-Tau (Thr231), and Tau Protein expression in mouse hippocampal tissues were conducted to analyze cognitive impairment. DHCB inhibited M1 polarization of BV2 cells and mediated anti-inflammatory M2 polarization, further alleviating inflammatory damage. DHCB also alleviated cognitive impairment in mice dose-dependently by promoting the polarization of M1 to M2 microglia in the hippocampal CA1 region. DHCB targeted and inhibited the expression of Lck/Yes-related novel protein tyrosine kinase (Lyn) protein in microglia, thereby suppressing p38 MAPK signaling transduction. Reactivating Lyn reversed the above benefits of DHCB. Similarly, p38 MAPK signal inhibitor SB 202190 opposed the proinflammatory polarization of BV2 cells and inflammatory damage mediated by Lyn overexpression. In conclusion, our study demonstrates that DHCB inhibits Lyn expression in microglia, thereby suppressing p38 MAPK signal transduction and accelerating the polarization of microglia from M1 to M2 phenotype to alleviate sevoflurane-induced POCD.

Cognitive dysfunction; Dehydrocorybulbine; Microglia; Sevoflurane; p38 MAPK signaling.