Salidroside and Compound C combination for treatment of cerebral ischemia-reperfusion injury by remodeling gut microbiota to regulate the brain–gut barriers

Abstract Background: It was reported that Salidroside and AMPK inhibitor Compound C alone have therapeutic effects on ischemic stroke. This paper explores the effect of salidroside combined with Compound C on cerebral ischemia-reperfusion injury in rats and based on the intestinal microecology its mechanism of action. Methods: Male Sprague-Dawley rats were randomly divided into 5 groups: ①sham-operated group; ②model group; ③ Salidroside group; ④Inhibitor group; ⑤Salidroside + inhibitor group. The rats in each group were given prophylactic intraperitoneal injection or normal saline for 7 days, and then the MCAO model was established. After the model was successfully established, each group continued to be treated with the corresponding solution for 7 days. After the last administration, the neurological function of the rats was detected, and then the whole brain was taken for sectioning, and the cerebral infarction area was measured after triphenyltetrazolium chloride staining; the brain tissue and colon tissue were taken for section analysis and Hematoxylin-Eosin staining; serum D-LA FABP, LPS, LBP concentration , DAO activity , IFN-γ, TNF-α, IL-6 and IL-10 concentration were detected by Elisa; claudin-5 mRNA, occludin mRNA and zo-1 mRNA expression levels were detected by Real-time PCR; gut microbiota analysis by 16S rRNA amplicon sequencing. Results: SAL and CC combination improved neurological function and relieved cerebral infarction; SAL and CC combination affected the α and β diversity of gut microbiota, increased beneficial bacteria, reshaped the gut microbiome and improved gut microbial dysbiosis; SAL and CC combination improved the histopathology of rat brain and colon, prevented the destruction of the brain-gut barrier. SAL and CC combination reversed the translocation of gut microbiota, reduced systemic inflammatory response. Conclusion: SAL and CC combination can reduce cerebral ischemia-reperfusion injury by regulating gut microbiota and brain-gut barrier.