A near-infrared fluorescent probe for hypochlorous acid enables high-content screening of natural products for hypertension intervention.

Abstract

Hypertension is accompanied by persistent oxidative stress and inflammatory activation, which contribute to vascular dysfunction and target-organ injury. Hypochlorous acid (HClO), a highly reactive oxidant generated through the myeloperoxidase pathway, may serve as a molecular indicator of hypertension-associated oxidative and inflammatory damage. Herein, we developed OX-MT, an HClO-responsive near-infrared fluorescent probe, and integrated it with high-content imaging for the screening of natural products with potential antihypertensive activity. OX-MT enabled rapid (10 s), selective, and sensitive (LOD 20.4 nM) detection of HClO via an oxidative cleavage-triggered fluorescence turn-on at 680 nm. It was successfully applied for imaging exogenous and endogenous HClO in RAW264.7 macrophages. Using OX-MT as a high-content readout, procyanidins were identified from a natural product library that reduced HClO-associated fluorescence in angiotensin II-stimulated cells. In hypertensive mice, procyanidin treatment attenuated blood pressure elevation, reduced OX-MT signals in vivo and ex vivo, and partially alleviated aortic and renal histopathological damage in a dose-dependent manner. Collectively, this study establishes a probe-guided strategy that links HClO-associated oxidative imaging with high-content phenotypic screening and in vivo validation, providing a practical approach for identifying natural products with potential therapeutic value against hypertension.