Background

Herpes 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.

Methods

HSV-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.

Results

After 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.

Conclusions

In 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.

中文翻译：

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山奈酚-3-O-鼠李糖苷对HSV-1脑炎的体内外抗炎作用

背景

单纯疱疹病毒性脑炎（HSE）是由单纯疱疹病毒（HSV）引起的急性中枢神经系统传染病。目前，HSE感染尚无有效的治疗方法，会产生许多促炎因子。Kaempferol-3-O-rhamnoside (K-3-rh) 是一种植物类黄酮。本研究探讨了K-3-rh对HSV-1诱导的脑炎的抗炎作用。

方法

HSV-1 与 VERO 细胞共培养。将细胞分为四组，包括对照组、病毒组、K-3-rh组、黄芪多糖（APS）组和地塞米松组。流式细胞仪分别用于确定细胞凋亡。分别通过蛋白质印迹和 qRT-PCR 估计蛋白质和 mRNA。

结果

病毒感染后，细胞因子明显增加。K-3-rh干预后，小胶质细胞中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和一氧化氮（NO）的表达低于病毒组，并且白细胞介素10（IL-10）的表达没有变化。病毒感染后细胞凋亡率明显增加，K-3-rh可抑制病毒诱导的小胶质细胞凋亡。小胶质细胞凋亡的诱导是通过细胞色素c和 caspase-9 介导的线粒体途径实现的。此外，各药物干预组小鼠脑组织的病理变化均有所缓解。

结论

总之，K-3-rh 有可能通过减少小胶质细胞促炎因子的分泌、诱导小胶质细胞凋亡以及通过细胞色素C和 caspase-3 途径来减轻 HSV-1 诱导的脑损伤。