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Original Article | Open Access

Integrated network pharmacology and experimental verification to explore the mechanism of Sangqi Qingxuan formula against hypertensive vascular remodeling

Lingling Lia, Jiayun Wub, Ruiqi Yaoa, Deshuang Yanga, Ying Chena, Jin Zhanga, Li Huangc()
School of Postgraduate, Beijing University of Chinese Medicine, Beijing, 102488, China
Department of Cardiology, Beijing University of Chinese Medicine Shenzhen Hospital (Longgang), Shenzhen, 518172, China
Department of Integrative Cardiology, China-Japan Friendship Hospital, Beijing, 100029, China

Peer review under responsibility of Beijing University of Chinese Medicine.

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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 spontaneously hypertensive rat model, while the mechanism of SQQX on HVR was validated by immunohistochemistry (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 pressure 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.

Keywords

Sangqi Qingxuan formulaNetwork pharmacologyHypertensive vascular remodelingAction mechanismExperimental verificationSpontaneously hypertensive ratsPhenotypic transformationERK/MAPK pathway

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Journal of Traditional Chinese Medical Sciences
Volume 9 Issue 3,
July 2022
Pages 277-288
DOI: 10.1016/j.jtcms.2022.06.007
Cite this article:
Li L, Wu J, Yao R, et al. Integrated network pharmacology and experimental verification to explore the mechanism of Sangqi Qingxuan formula against hypertensive vascular remodeling. Journal of Traditional Chinese Medical Sciences, 2022, 9(3): 277-288. https://doi.org/10.1016/j.jtcms.2022.06.007
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