Network pharmacology and validation by experiment of Shuerjing Capsule in the treatment of primary dysmenorrhea / 国际中医中药杂志

ABSTRACT

Objective:To explore the mechanism of Shuerjing Capsule in treating primary dysmenorrhea based on molecular docking of network pharmacology and in vivo experiment.Methods:By using TCMSP to screen the active components and targets of Shuerjing Capsule; by using GeneCards and DrungBank databases to retrieve targeted proteins of primary dysmenorrhea, and the intersection targets of drugs and diseases were obtained through Weishengxin online platform; by using Cytoscape 3.9.1 software to produce component-target network of Shuerjing Capsule for the treatment of primary dysmenorrhea; by STRING databases to construct drug-disease target PPI network; by DAVID database to perform GO and KEGG pathway enrichment analysis.The key active components of the drug and the core targets of the disease were obtained with molecular docking. The rats were randomly divided into control group, model group, the low-dose group, medium-dose group and high-dose group of Shujing Capsule (0.15, 0.21, 0.42 g/kg), and ibuprofen group (20 mg/kg), with 10 rats in each group. The animal model of primary dysmenorrhea was established by subcutaneous injection of estradiol benzoate and intervented by drugs. The number of writhing reaction, uterine contractile inhibition rate and uterine index of rats were observed. The expressions of TNF-α, IL-6 and IL-1 in serum and the levels of PTGS2 and VEGFA in uterine tissue were detected by ELISA.Results:A total of 188 active ingredients of Shuerjing Capsule were screened, and 51 targets of Shuerjing Capsule and primary dysmenorrhea were identified. TNF, IL-6, AKT1 and TP53 may be the key targets of Shuerjing Capsule in the treatment of primary dysmenorrhea. A total of 519 GO biological processes and 119 related signaling pathways were obtained, among which estrogen, IL-17, HIF-1 and other signaling pathways were closely related to the treatment of primary dysmenorrhea. The results of molecular docking were good, among which stigmasterol had the strongest binding ability to TP53. The experimental results showed that compared with the model group, the uterine index and the number of torsion were decreased in the low -, medium - and high-dose Shuojing Capsule groups ( P<0.05), the uterine contraction inhibition rate increased ( P<0.05); Serum levels of TNF-α, IL-6 and IL-1 of medium and high dose group decreased ( P<0.05), the levels of PTGS2 and VEGFA in uterine tissues decreased ( P<0.05). Conclusion:Shuerjing Capsule has the effect of anti-inflammatation and improveing hypoxia, which may be related to the inhibition of TNF-α, IL-6 and IL-1 inflammatory factors in serum and the expression of PTGS2 and VEGFA proteins in uterine tissues.