The Mechanism Actions of Astragaloside IV Prevents the Progression of Hypertensive Heart Disease Based on Network Pharmacology and Experimental Pharmacology

Haoran Jing; Rongsheng Xie; Yu Bai; Yuchen Duan; Chongyang Sun; Ye Wang; Rongyi Cao; Zaisheng Ling; Xiufen Qu

doi:10.3389/fphar.2021.755653

The Mechanism Actions of Astragaloside IV Prevents the Progression of Hypertensive Heart Disease Based on Network Pharmacology and Experimental Pharmacology

Front Pharmacol. 2021 Nov 5:12:755653. doi: 10.3389/fphar.2021.755653. eCollection 2021.

Authors

Haoran Jing¹, Rongsheng Xie¹, Yu Bai¹, Yuchen Duan¹, Chongyang Sun², Ye Wang¹, Rongyi Cao³, Zaisheng Ling⁴, Xiufen Qu¹

Affiliations

¹ Department of Cardiovascular, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
² Department of CT, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
³ Blood Transfusion Department, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
⁴ Department of CT, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Abstract

Astragaloside IV (AS-IV) has been used to treat cardiovascular disease. However, whether AS-IV exerts a protective effect against hypertensive heart disease has not been investigated. This study aimed to investigate the antihypertensive and cardioprotective effects of AS-IV on L-NAME-induced hypertensive rats via network pharmacology and experimental pharmacology. The network pharmacology and bioinformatics analyses were performed to obtain the potential targets of AS-IV and hypertensive heart disease. The rat hypertension model was established by administrated 50 mg/kg/day of L-NAME for 5 weeks. Meanwhile, hypertension rats were intragastrically administrated with vehicle or AS-IV or fosinopril for 5 weeks. Cardiovascular parameters (systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rates, and body weight), cardiac function parameters (LVEDd, LVEDs, and fractional shortening), cardiac marker enzymes (creatine kinase, CK-MB, and lactate dehydrogenase), cardiac hypertrophy markers (atrial natriuretic peptide and brain natriuretic peptide), endothelial function biomarkers (nitric oxide and eNOS), inflammation biomarkers (IL-6 and TNF-α) and oxidative stress biomarkers (SOD, MDA, and GSH) were measured and cardiac tissue histology performed. Network pharmacological analysis screened the top 20 key genes in the treatment of hypertensive heart disease treated with AS-IV. Besides, AS-IV exerted a beneficial effect on cardiovascular and cardiac function parameters. Moreover, AS-IV alleviated cardiac hypertrophy via down-regulating the expression of ANP and BNP and improved histopathology changes of cardiac tissue. AS-IV improved endothelial function via the up-regulation of eNOS expression, alleviated oxidative stress via increasing antioxidant enzymes activities, and inhibited cardiac inflammation via down-regulating IL-6 and TNF-α expression. Our findings suggested that AS-IV is a potential therapeutic drug to improve L-NAME-induced hypertensive heart disease partly mediated via modulation of eNOS and oxidative stress.

Keywords: antioxidant; astragaloside IV; cardiac damage; hypertensive heart disease; inflammation; network pharmacology.