Clinical Observation Of Danggui Sini Decoction In The Treatment Of Migraine With Blood Deficiency And Cold Coagulation And Its Mechanism Based On Network Pharmacology

Objective: Through clinical trials,this study objectively evaluated the efficacy and safety of Danggui Sini Decoction in the treatment of blood-deficiency and cold-coagulation migraine,providing preliminary evidence-based evidence for the treatment of migraine and more clinical data for the clinical treatment of migraine.Secondly,the mechanism of action of Danggui Sini Decoction in the treatment of migraine was analyzed through network pharmacology,and elaborated from the aspects of TCM active ingredients-disease targets-treatment pathways,etc.,to provide certain ideas and directions for subsequent verification experiments.Methods:1.From December 2021 to December 2022,126 outpatients who met the inclusion criteria of blood deficiency and condensing migraine were stochastically separate into observation group receiving plus or minus treatment with Danggui Sini Decoction,and control group receiving treatment with sibillin,both of which were 63 cases,for a total of 4 weeks,during which medication,symptoms and adverse reactions were asked.The efficacy of the two groups was also evaluated by monitoring patients’ migraine VAS scores,symptom scores and TCM evidence scores before and 1 month after treatment.2.The main effective chemical constituents and action targets of Danggui Sini Decoction were obtained through TCMSP database and ADME screening,and the network diagram of "TCM-active ingredient-action target" was constructed to screen out the key active ingredients with higher degree value.Drug targets were matched with migraine-related disease targets obtained from Gene Cards,Drug Bank,OMIM and TTD databases.The STRING platform was used to analyse the PPI network to find target interactions and identify key targets.The DAVID was used to enrich the GO function and the KEGG pathway of key targets and to construct an "agent-key target-pathway" network.Molecular docking between the key target protein and the key active substance was performed using AUTODOCK and then docking models were drawn in the form of hydrogen bonds using Pymol software.Results:1.Clinical trial study: 126 cases were included in this study,8 cases fell off,and a total of 118 cases were counted(60 cases in the observation group treated with Danggui Sini Decoction and 58 cases in the control group treated with sibillin).Baseline characteristics such as sex,age,disease duration,VAS score,symptom score and TCM syndrome score were not significantly different between the two groups before treatment(P > 0.05)and could be compared.There were differences in reducing migraine VAS score,severity,attack frequency,duration,symptom score and TCM syndrome score between two groups(P <0.05).In terms of the clinical effect of migraine,the total effective rate of the observation group was 81.67%;and the control group was 65.52%,there difference was statistically significant(P<0.05),and the curative effect of former was superior to latter in all aspects.In terms of adverse reactions,there was no adverse reaction in the observation group,and 1 case in the control group was rated as grade 2 in safety evaluation,manifested as drowsiness.2.Network pharmacological research: Danggui Sini Decoction contained 266 kinds of active ingredients such as glycyrrhizol,paeoniflorin,paeoniflorin,quercetin,kaempferol and other active ingredients acting on 79 targets such as ALB,IL6,TNF,IL-1β,among which the four key active ingredients with the highest degree value were quercetin,kaempferol,β-sitosterol and soybean sterol.After screening,17 key targets of Danggui Sini decoction for migraine were obtained,involving 244 GO items,including 190 biological processes,mainly involving cytokine mediated signaling pathway,response to glucocorticoid and positive regulation of glial cell proliferation.There were15 cells,mainly involving nucleus,cytoplasm,cytoplasm and projective neurons.There are 39 molecular functions,mainly involved in transcription factor binding,cytokine activity and enzyme reaction.There were 91 KEGG signaling pathways,mainly involving IL-17,TNF,AGE-RAGE,C-type lectin receptor(CLR)and MAPK signaling pathways in diabetes complications.The molecular docking results showed that the core target proteins dovetailed well with the key active ingredients of Danggui Sini Decoction.Conclusion:1.Danggui Sini Decoction has significant,safe and reliable efficacy in treating blood deficiency and cold coagulation type migraine,which can effectively relieve headache degree of migraine patients,reduce headache attack frequency and duration,reduce TCM syndrome score of blood deficiency and cold coagulation,and improve patients’ quality of life.However,due to the limitation of time and region in this study,more relevant studies with sufficient samples,wide area and standard operation should be conducted in the future,and relevant laboratory test indicators should be added.2.Quercetin,kaempferol,β-sitosterol and stigmasterol in Danggui Sini decoction can regulate multiple signaling pathways such as IL-17,TNF,AGE-RAGE,CLR and MAPK by acting on multiple targets such as ALB,IL6,TNF and IL1 B.To realize the role of multiple components,objectives and pathways in the treatment of blood-deficiency and cold-coagulation migraine,the conclusion still needs to be further verified by basic experiments.