Integrative network pharmacology and experimental study of Qingda granule in hypertension-induced endothelial dysfunction.

Abstract

Endothelial dysfunction (ED) plays a pivotal role in the pathogenesis of hypertension and its associated vascular complications. Qingda granule (QDG) exhibits significant antihypertensive properties and demonstrates therapeutic potential in ameliorating vascular dysfunction. This study aimed to explore QDG's role in alleviating endothelial injury in hypertension. An L-NAME (Nω-Nitro-L-arginine methyl ester)-induced hypertensive mouse model was used to evaluate the effects of QDG on blood pressure and endothelial function. Endothelial function was assessed through histological analysis, nitric oxide (NO) quantification, and vascular response measurements. To explore underlying mechanisms, network pharmacology was conducted using databases such as HERB, SwissTargetPrediction and STRING. Key pathways related to inflammation and cell adhesion were identified. Based on these findings, immunohistochemical staining was conducted to analyze the expression of phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 (p-NF-κB p65), NF-κB p65, intercellular adhesion molecule-1 (ICAM-1), and tumor necrosis factor-α (TNF-α) in vascular tissues. QDG treatment significantly reduced blood pressure, increased NO levels, and enhanced endothelial nitric oxide synthase (eNOS) expression in L-NAME-induced hypertensive mice, indicating its potential to restore endothelial function. Experimental validation further confirmed that QDG markedly suppressed the expression of p-NF-κB p65, TNF-α, and ICAM-1 in vascular tissues. These results suggest that QDG alleviates hypertension-induced ED primarily by inhibiting inflammation and endothelial adhesion via the NF-κB signaling pathway. Overall, QDG presents a promising therapeutic candidate for managing hypertension and its vascular complications.