Calycosin regulates gut microbiota-bile acid-FXR axis to protect rats from cerebral ischemia-reperfusion injury

Recent reports have shown that metabolites derived from gut microbiota play a vital role in intestinal diseases, immune regulation, and neuroinflammation. Nowadays, calycosin has been revealed the protective mechanism from different perspectives on cerebral ischemia-reperfusion injury (CIRI), while the effect of gut microbiota-bile acid-farnesoid X receptor (FXR) axis on the inflammatory protection of CIRI has not been explored. To this end, we established a middle cerebral artery occlusion (MCAO) model firstly to assess the protection of calycosin in CIRI through neurological deficit scoring, TTC staining, and HE staining. Secondly, 16s RNA sequencing, ELISA, real-time qPCR, Western blot, and total bile acid (TBA) detection kit were utilized to detect the pharmacology of calycosin on MCAO rats. Our data indicated that calycosin could significantly improve nerve function scores, reduce cerebral infarction volume, lower serum levels of IL-10, IL-17 inflammatory factors, and TBA, increase mRNA and protein levels of ZO-1 and Occludin in brain, as well as FXR, ZO-1 and Occludin levels in colon. In summary, calycosin can exert a neuroinflammatory protective effect on CIRI in rats via regulating the gut microbiota to improve bile acid metabolism.