Anti-inflammatory effects of kaempferol-3-O-rhamnoside on HSV-1 encephalitis in vivo and in vitro

Abstract

BACKGROUND\nHerpes simplex virus encephalitis (HSE) is an acute central nervous system infectious disease caused by herpes simplex virus (HSV). Currently, there is no effective treatment for HSE infection, which produces many pro-inflammatory factors. Kaempferol-3-O-rhamnoside (K-3-rh) is a plant flavonoid. This study was investigated the anti-inflammatory effect of K-3-rh on encephalitis induced by HSV-1.\n\n\nMETHODS\nHSV-1 was co-cultured with VERO cells.Cells were divided into four groups, including the control group, virus group, K-3-rh group, Astragalus polysaccharide (APS) group and dexamethasone group. Flow cytometry were utilized to determine cell apoptosis, respectively. Proteins and mRNAs were estimated by western blot and qRT-PCR, respectively.\n\n\nRESULTS\nAfter viral infection, the cytokines were significantly increased. After K-3-rh intervention, the expression of Tumor necrosis factor-α (TNF-α), interleukin-1 beta(IL-1β), and nitric oxide(NO) in microglia were reduced contrast with those in the virus group, and the expression of interleukin-10(IL-10) did not change. After viral infection, the apoptotic rate increased significantly, and K-3-rh could inhibit viral-induced apoptosis in the microglial cell line. The induction of microglia apoptosis was achieved by cytochrome c and caspase-9-mediated mitochondrial pathway. Also, the pathological changes of brain tissue in mice of each drug intervention group were alleviated.\n\n\nCONCLUSIONS\nIn conclusion, K-3-rh had the potential to reduce HSV-1-induced brain injury by reducing the secretion of microglial pro-inflammatory factors, inducing apoptosis of microglia cells, and through cytochrome C and caspase-3 pathway.