Mechanism of Wuweijiangyasan in the treatment of spontaneous hypertension based on network pharmacology

Background: Hypertension affects over 1 billion people globally and is the top risk factor of cardiovascular morbidity and mortality.Wuweijiangyasan（WWJYS）, as an empirical prescription, has stable depressurization effects. This study investigated the chemical composition and pharmacodynamic effects of WWJYS in regulating the blood pressure（BP）, emotion, and blood lipid of spontaneous hypertensive rats,and further explored the depressurization mechanism of WWJYS. Materials and Methods: This study used network pharmacology to identify the origins and predict targets of WWJYS, and artificial intelligence-based molecular docking is used to further predict targets and mechanisms. The chemical constituents of WWJYS were analyzed and identified by ultra high-performance liquid chromatography–mass spectrometry（MS）/MS. Results: In the WWJYS group, the systolic BP level significantly was decreased, and the HR was stable. The irritability became stable after the 5-week treatment compared with the model group（P ＜ 0.05）. Rats’ rotation tolerance time increased after 2-weeks stabilization. Compared with the model group, angiotensin-converting enzyme 2 protein and mRNA of the WWJYS group increased significantly（P ＜ 0.05）. Network pharmacology collected 64 compounds and identified 22 potential targets of WWJYS for antihypertensive activity. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that WWJYS might regulate smooth muscle cells, affect inflammatory response and improve endothelial function through multiple pathways. The molecular docking study further supported that the target proteins have good combinations with the main active components of WWJYS. Conclusions: The data indicated that WWJYS had significant depressurization, analgesic, and sedative, as well as lipid-lowering effects, and the depressurization mechanism of WWJYS may function in multiple signal pathways, especially in improving blood vessel function and intervening inflammation.