[Mechanism of Jingangteng Capsules in ameliorating chronic nonbacterial prostatitis based on gut microbiota and metabolomics].

Based on the experimental autoimmune prostatitis(EAP) rat model, this study investigated the effects and mechanisms of Jingangteng Capsules(JGTCs) in ameliorating chronic nonbacterial prostatitis(CNP) to lay a foundation for the development of improved new drugs with expanded indications for JGTCs. Hematoxylin-eosin(HE) staining was used to observe pathological changes in the prostate tissue of rats. A microscope was used to measure the number of white blood cells and the density of lecithin bodies in prostate tissue homogenates. Biochemical analysis was employed to detect the levels of superoxide dismutase(SOD) and malondialdehyde(MDA) in serum. Enzyme-linked immunosorbent assay(ELISA) was used to measure the level of inflammatory factors in serum. The 16S rDNA sequencing was applied to explore the effect of JGTCs on the changes in intestinal microbiota. Non-targeted metabolomics was used to predict the mechanism of JGTCs in ameliorating CNP. Western blot(WB) was utilized to validate the effects of JGTCs on the sphingosine kinase 1(SPHK1)/sphingosine-1-phosphate receptor 1(S1P1)/phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt) pathway. The results show that JGTCs can ameliorate pathological injury of the prostate, enhance the density of lecithin bodies, reduce the number of white blood cells, decrease the levels of pro-inflammatory factors in serum, including tumor necrosis factor alpha(TNF-α), inducible nitric oxide synthase(iNOS), interleukin(IL)-1β, IL-6, IL-8, and IL-2, and increase the level of anti-inflammatory factor IL-10. JGTCs can modulate the structure of intestinal microbiota, increase the relative abundance of Lactobacillus and Bifidobacterium animalis, and decrease the relative abundance of unclassified＿f＿Prevotellaceae and Veillonella. JGTCs can alter the content of 10 metabolites, including sphingosine and retinoyl β-glucuronide and be involved in five metabolic pathways such as sphingolipid metabolism and retinol metabolism. The WB experiment reveals that JGTCs can inhibit the expressions of SPHK1 and S1P1 and the phosphorylation of PI3K and Akt. The results indicate that JGTCs can significantly alleviate inflammatory injury in the prostate tissue of EAP rats. Its mechanism may involve regulating intestinal microbiota dysbiosis and metabolic disorders and inhibiting the activation of the SPHK1/S1P1/PI3K/Akt signaling pathway.