Clinical Observation And Network Pharmacological Study Of Da Chaihu Decoction In The Treatment Of Hypertension With Liver-fire Hyperactivity Syndrome

Objective:Through observing the clinical effect,safety and the inhibition to inflammatory response of Da Chaihu Decoction in the treatment of patients with grade-1 hypertension with liver-fire hyperactivity syndrome,the clinical application value of Da Chaihu Decoction is here to be explored.Meanwhile,combined with the research strategy of network pharmacology,a systematic analysis of Da Chaihu Decoction will be made,with a deep research into the action mechanism of Da Chaihu Decoction regarding to its treatment to hypertension.Methods:1.The clinical trial observation: We selected 72 patients with grade-1hypertension with liver-fire hyperactivity syndrome who were diagnosed and treated in Cardiology Department of Shandong Province of TCM from June2020 to December 2020.We divided the 72 patiently randomly into the experimental group(n=36)and the control group(n=36).The experimental group was given Da Chaihu granules,one dose each day,and the control group was treated with Valsantan(Daivin),80 mg daily for 4 weeks.The blood pressure,24-hour dynamic blood pressure,resting heart rate,TCM syndrome score,quality of life assessment and the expression levels of inflammatory factors(hs-CRP,TNF-α,IL-6,IL-10,IL-1β,PTGS2)in the two groups were observed before and after the treatment.The ultimate objective is to evaluate the effect and safety of Da Chaihu Decoction in the treatment of patients with grade-1 hypertension with liver-fire hype-ractivity syndrome.2.The network pharmacology: Based on traditional Chinese medicine system pharmacology platform(TCMSP)and Pub Chem databases,the chemical composition and targets of Da Chaihu Decoction were screened.The targets of corresponding gene of hypertension were searched through 6databases.We constructed the mapping network between diseases and drugs of Da Chaihu Decoction in the treatment of hypertension.The straight targets of Da Chaihu Decoction in the treatment of hypertension were analyzed by using the biological software of String,Cytoscape3.6.1 and David.Meanwhile,the biological function analysis and disease pathway analysis of the direct acting targets were carried out to explore the potential mechanism of Da Chaihu Decoction in the treatment of hypertension.Meanwhile,Auto Dock Vina software was used for molecular docking and key targets proteins respectively.Results:1.Clinical trial results:1.1(1)Clinic blood pressure: the clinical blood pressure in the experimental group and the control group were significantly changed before and after treatment(P<0.01).The total rate of antihypertensive effect in the test group was 83.3%,and that in the control group was 90.1%,with statistically significant difference between groups(P < 0.01).(2)24-hour ambulatory blood pressure: SBP and DBP in day,night and 24 hours in both groups decreased,compared with the two values(SBP and DBP)before intervention,with statistically significant differences(P < 0.01).After intervention,there were statistically significant differences in d SBP,d DBP,n SBP,24 h SBP and 24 h DBP among groups(P < 0.05),but no statistically significant differences in n DBP(P>0.05).1.2(1)In terms of the clinical symptoms improvement via TCM,the total rate of in the experimental group was 93.3%,and that in the control group was70.1%,with statistically significant difference between groups(P<0.05).The single and total scores of TCM symptoms in the two groups were lower than before,and the experimental group was lower than the control group,with statistical significance between groups(P < 0.05).(2)Compared with the situation before intervention,the quality of life in both groups was significantly improved,with statistically significant difference within groups(P<0.01).The experimental group was better than the control group,and the difference between the two groups was statistically significant difference(P<0.01).1.3 Expression of inflammatory reaction: after treatment,serum levels of pro-inflammatory factors hs-CRP,TNF-α,IL-6,IL-1β and PTGS2 in 2 groups decreased with statistically significant differences(P< 0.01).The level of anti-inflammatory factor IL-10 increased between the two groups,and the difference was statistically significant(P < 0.01).After intervention,the concentrations of hs-CRP,TNF-αand IL-6 in the experimental group were lower than those in control group,with statistical significance(P<0.05).IL-10 concentration in experimental group was higher than that in control group,and the difference was statistically significant(P<0.05).Levels of IL-1β and PTGS2 decreased similarly between the two groups,and the difference was not statistically significant(P>0.05).1.4 Safety: during the treatment period,6 patients in the test group showed clinical manifestations of loose stools,and no serious adverse effect occurred in the rest.No abnormalities were found in the two groups in terms of safety.2.Network pharmacological analysis: we sifted out 97 active ingredients and 170 potential targets from Da Chaihu Decoction.There are 18253 related targets in hypertension.and 157 targets of direct interaction between drugs and diseases.We obtained 19 key targets about Da Chaihu Decoction in its treatment to hypertension,including IL-6、TNF、PTGS2、VEGF、NOS3,and so on.KEGG pathway enrichment analysis has found 117 signaling pathways,among these pathways,and 19 pathways were closely related to the development of hypertension.TNF signaling pathway,Neuroactive ligandreceptor interaction,Calcium signaling pathway,VEGF signaling pathway were the hinge of the whole hypotensive mechanism of Da Chaihu Decoction.A total of four key active ingredients were docked with four key targets.Conclusion:1.Da Chaihu Decoction has a certain antihypertensive effect to the arterial pressure of patients with grade-1 hypertension with liver-fire hyperactivity syndrome,while its comprehensive effect is less than that of the Valsantan.Therefore,Da Chaihu Decoction can reduce the resting heart rate of patients,improve the clinical symptoms of Chinese medical symptoms,improve the quality of life,and inhibit the inflammatory response to a certain extent,which has good clinical effect and safety.2.The potential mechanism of action of Da Chaihu decoction in the treatment to hypertension involves multi-components,multi-targets and multipathways.It indicated that Da Chaihu Decoction could regulate inflammatory reaction,improving vascular endothelial function,collaborating calcium transport and adjusting neuroactiver eceptors,resulting in antihypertensive effect.Molecular docking showed that Quercetin,Kaempferol and other active ingredients have good binding ability with key targets IL-6,TNF,PTGS2 and IL-1β.