Integrated network pharmacology and experimental verification to explore the mechanism of Sangqi Qingxuan formula against hypertensive vascular remodeling
- Author:
Li LINGLING
1
;
Wu JIAYUN
;
Yao RUIQI
;
Yang DESHUANG
;
Chen YING
;
Zhang JIN
;
Huang LI
Author Information
1. School of Postgraduate,Beijing University of Chinese Medicine,Beijing,102488,China
- Keywords:
Sangqi Qingxuan formula;
Network pharmacology;
Hypertensive vascular remodeling;
Action mechanism;
Experimental verification;
Spontaneously hypertensive rats;
Phenotypic transformation;
ERK/MAPK pathway
- From:
Journal of Traditional Chinese Medical Sciences
2022;9(3):277-288
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the bioactive components of Sangqi Qingxuan formula(SQQX),predict the pharmacological targets,and explore the mechanism of hypertensive vascular remodeling(HVR).Methods:Network pharmacology was adopted to predict how SQQX acts in HVR.The effectiveness was assessed by blood pressure measurements and pathological morphology observation based on a spon-taneously hypertensive rat model,while the mechanism of SQQX on HVR was validated by immuno-histochemistry(IHC)and western blot(WB)according to the results of network pharmacology.Results:There were 130 bioactive components of SQQX and 231 drug targets predicted by the Traditional Chinese Medicine Systems Pharmacology Database.Subsequently,181 common targets were identified for SQQX against HVR,with TP53,MAPK1,and AKT1 as the core targets.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses was employed to identify the top 20 enriched functions and the top 20 pathways(P＜.01).Finally,the key role of the ERK/MAPK signaling pathway in HVR was determined.The in vivo results suggested that SQQX reduced systolic blood pres-sure and increased the ratio of thoracic aortic wall thickness to lumen diameter.Additionally,compared with the model group,SQQX increased the expression of smooth muscle 22 alpha(IHC:P＜.001;WB:P＜.05)and decreased the expression of osteopontin(IHC:P＜.001;WB:P＜.05),ERK1/2(IHC:P＜.001;WB:ERK1&ERK2,all P＜.05),p-ERK1/2(IHC:P＜.001;WB:ERK1&ERK2,all P＜.05),and the ratio of p-ERK1/2 to ERK1/2 protein(IHC:P＜.001).Conclusions:SQQX,which has multiple bioactive ingredients and potential targets,is an effective treatment for HVR.The mechanism of antihypertensive and vascular protection may be related to the inhibition of phenotypic transformation of vascular smooth muscle cells and the ERK/MAPK signaling pathway.
