Therapeutic Effects of Jiedu Huoxue Decoction in Chronic Prostatitis/Chronic Pelvic Pain Syndrome: Network Pharmacology, Molecular Docking and Experimental Evidence

Background: Jiedu Huoxue decoction (JDHXD) can be effectively alleviated chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) patients’ pelvic pain, lower urinary tract symptoms, and other discomforts. But its mechanism of action involving multi-component, multi-target and multi-pathway is unclear. Objectives: Integrated strategy of network pharmacological prediction, molecular docking, and experimental validation elucidate potential mechanism of JDHXD in treating CP/CPPS. Study design and methods: Two traditional Chinese medicine systems pharmacology databases and three disease related databases were applied to identify the herbs active components and the putative targets of CP/CPPS. Using the Cytoscape to constructed and analysis the herbs-compounds-targets network. Subsequently, the protein-protein interaction (PPI) was investigated by STRING database. Using DAVID databases to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The binding of core active compounds with hub targets were assessed by molecular docking. Furthermore, in vivo efficacy of JDHXD was validated in CP/CPPS rat model. The key signal pathway of network pharmacological prediction would be validated by animal experiment. Result: In total, 149 active compounds of 10 Chinese herbals and 909 potential CP/CPPS-related targets were identified. Network pharmacology revealed 161 common targets between 136 potential active compounds and CP/CPPS. After topology analysis, 5 core active compounds and 18 hub targets have been screened. PPI analysis obtained 18 hub targets. Based on enrichment analysis of 161 targets, we obtained GO function 277 items and KEGG pathway 114 items. Molecular docking verification shown that the top 5 hub targets were well binding with 5 core active compounds. Animal experiment shown that JDHXD had protective effect on CP/CPPS. JDHXD can significantly down-regulated the key gene expression (JNK, ERK1/2 and P38) and inhibit phosphorylation of ERK1/2，JNK and P38 in the MAPK signaling pathway. Conclusions: : This study demonstrated potential mechanism of JDHXD in treating CP/CPPS. Network pharmacological, molecular docking and experimental verification revealed its multi-component, multi-target and multi-pathway treatment characteristics. The reliability and effectiveness of those method are very helpful to explore the material basis and mechanism of traditional Chinese medicine.