Uncovering The Molecular Mechanism Of Wenjing Decoction In The Treatment Of Primary Dysmenorrhea Based On Network Pharmacology

Background and Purpose Primary dysmenorrhea is a common functional gynecological disease,which accounts for the majority of dysmenorrhea.It causes severe pain and many other symptoms,which troubles women a lot.At present,there are mainly 3 kinds of drugs to treat primary dysmenorrhea.These drugs include non-steroidal anti-inflammatory drugs,oral contraceptives and calcium channel blockers.Although they can alleviate pain,they have poor curative effect on symptoms such as fatigue,weakness,anxiety,insomnia and dizziness.These drugs will cause many adverse reactions,such as gastric ulcer,dysfunction of liver and kidney,cerebral thrombosis,hypotension and so on.Therefore,a better therapy is needed to help these women out of this annoying disease.Wenjing decoction,a traditional herbal formula,plays an important role in the treatment of gynecological diseases in China.It is recorded in a medical classic,the Golden Chamber.This herbal formula mainly contains 12 herbs like evodia rutaecarpa,cinnamomi ramulus,angelicae sinensis radix,cortex moutan,ligusticum wallichii,ginseng,colla corii asini,paeoniae radix alba,ophiopogonis radix,zingiber officinale roscoe,arum ternatum thunb and glycyrrhiza uralensis fisch.It is mainly used to treat cold and deficiency of Chong and Ren Channels as well as blood-stasis syndrome.A large number of clinical trials have proved that Wenjing decoction can significantly alleviate symptoms of primary dysmenorrhea.At the same time,Wenjing decoction has less side effects compared to the common drugs above.However,the mechanism has not been clear.This research aims to reveal the possible molecular mechanism of Wenjing Decoction in treating primary dysmenorrhea based on network pharmacology,which will provide a basis for experiment and make a contribution to development of new drugs and traditional Chinese medicine.Methods The chemical components of Wenjing Decoction and their targets were obtained from 3 common herbal databases like TCMSP,TCMID as well as TCMIP.The chemical components possible to be drugs were screened by refering to some pharmacological rules like Lipinski’s Rule of Five,oral bioavailability as well as drug likeness.The target genes of primary dysmenorrhea were obtained from GeneCards,a human gene database.Shared targets of Wenjing Decoction and primary dysmenorrhea were selected.The file about interaction of shared targets obtained from STRING,a common protein database,was put into Cytoscape and then a protein-protein interaction network(PPI)was constructed.GO enrichment and KEGG pathway enrichment were analyzed by DAVID.Cytoscape was used to draw a network of "pharmacological ingredients-shared targets",and topological analysis was performed to obtain a sub-network.Results In this research,we found 6 main pharmacological components like isorhamnetin,7-methoxy-2-methyl isoflavone,naringenin,kaempferol,baicalein,and rutaecarpine;4 main targets like PTGS1,PTGS2,PPARG and ESR1;7 important signaling pathways like pathway in cancer,proteoglycan in cancer,nonalcoholic fatty liver disease,chemical carcinogenesis,ovarian steroidogenesis,estrogen signaling pathway as well as microRNA in cancer.Conclusion This research successfully predicted the mechanism of Wenjing Decoction in treating primary dysmenorrhea,which is a complicated process involving many components,targets and pathways.