| ObjectiveTo test the efficacy and safety that Jiuwei Zhusheng Decoction can promote cervical ripening and predict the possible molecular mechanism and biological pathway of it based on the network pharmacology.MethodsIn a prospective and randomized trial,pregnant women who were undergoing induction of labor with unfavorable cervix(Bishop score<6),were randomly assigned to a study group or control group.The study group was given Jiuwei Zhusheng Decoction orally and the control group was given instructed breast massage and nipple stimulation.Three days later two groups of pregnant women were re-evaluate their cervical Bishop score and oral misoprostol tablets were given to promote cervical ripening for those cervical Bishop score<6 but not in labor.The primary outcome was cervical ripening,success rate of induction of labor,traditional Chinese medicine scale scores,postpartum hemorrhage,labor time,neonatal outcome,incidence of adverse events,etc.After clinical efficacy observation,the effective chemical components,targets and genes of Jiuwei Zhusheng Decoction were obtained in the TCMSP database platform while target genes of cervical ripening searched through GeneCards、OMIM、DisGeNET、DrugBank、TTD databases.The herb’s targets was compared with disease targets,and a Venn diagram of Jiuwei Zhusheng Decoction promoting cervical ripening was drawn late.The PPI network was constructed through the STRING database,and the regulatory network of "cervical ripening-genes-targets-Jiuwei Zhusheng Decoction" was constructed using Cytoscape 3.7.2 to select the core genes.Finally,GO and KEGG enrichment were done by Metascape database to analyze their biological processes,cellular components,molecular functions and KEGG pathways.ResultsFrom July 2019 through January 2021,70 women were randomized(35 study group,35 control group).Baseline characteristics were similar between groups,including age,hemoglobin value,gestational week,pregnancy times,delivery times,complications of pregnancy,cervical Bishop scores and the TCM syndrome scores(P>0.05).After 3 days of intervention,the cervical Bishop scores of the two groups increased compared with that before the intervention(P<0.01),but the cervical scores of the study group increased significantly compared with the control group(P<0.01),and the times of using misoprostol tablets was less than the control group(P<0.01).The study group had a significantly higher labor induction rate than the control group(study group:88.57%vs control group:45.72%).There was a significant difference that the total score of TCM syndromes related to Qi and blood deficiency in the study group was lower than that of the control group(P<0.01),and the total scores of TCM syndromes related to constipation were also lower than that of the control group after the intervention(P<0.01).The total effective rate of the group was significantly higher than that of the control group(study group:82.86%vs control group:14.29%),and the uncomfortable symptoms related to deficiency of both Qi and blood were significantly improved(P<0.01).The 2-hour postpartum bleeding and 24-hour postpartum bleeding volume in the study group were lower than those in the control group(P<0.05).The first,second,third and total labor time were not different between groups(P>0.05).The weight of the newborn and the Apgar score of the newborn at 1-5-10 minutes after birth were not significantly different between the two groups(P>0.05).No adverse drug reactions such as nausea,vomiting and diarrhea were found in both groups in response.There was a significant difference between the two groups in the incidence of adverse outcomes(study group:0%vs control group:17.14%).A total of 170 chemical components and 1900 targets were screened from Jiuwei Zhusheng Decoction through network pharmacology,and 53 targets related to cervical ripening.Key ingredients including kaempferol,β-sitosterol,stigmasterol,protoopioid,and ginsenoside,which are mainly found in renshen,danggui,and baishao.The key targets are PTGS2,PTGS1,ADRB2,PGR,SLC6A4 which are related to inflammation and hormone levels.After enrichment analysis of GO and KEGG pathways,it is found that Jiuwei Zhusheng Decoction mainly participates in immune response,inflammatory response,oxidative stress response(including response to lipopolysaccharide,response to oxidative stress,reactive oxygen metabolism process,and oxygen level response,leukocyte transfer,etc.)and other biological processes are involved in promoting cervical ripening.Jiuwei Zhusheng Decoction also through inflammatory response-related signaling pathways,endocrine hormone-related signaling pathways,improving blood circulation related pathways,and regulating oxygen levels related signaling pathways(including AGE-RAGE signaling pathway,IL-17 signal pathway,HIF-1 signal pathway,relaxin signal pathway,JAK-STAT signal pathway,etc.)to promote cervical ripening.ConclusionThe Jiuwei Zhusheng Decoction has the effect of "tonifying qi and blood,laxative and fetal".It can promote cervical ripening,increase the rate of natural childbirth and the success rate of labor induction,improve the symptoms of qi and blood deficiency and constipation in pregnant women,reduce postpartum hemorrhage,Improve pregnancy and childbirth outcomes,and has no obvious side effects on pregnant women and newborns.It is worthy of clinical promotion.The effective ingredients,targets and biological pathways of Jiuwei Zhusheng Decoction to promote cervical ripening reflect the characteristics of"multicomponent-multitarget-multipathway" of traditional Chinese medicine.It mainly participated in biological processes and signal pathways such as increasing endocrine hormone levels,triggering inflammation,improving blood circulation,and regulating oxygen levels,improving the intestinal microecology to promoting cervical ripening.Among them,improving blood circulation and regulating oxygen levels may also be the mechanism by which Jiuwei Zhusheng Decoction improves the symptoms of qi and blood deficiency in pregnant women. |
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