The antihypertensive effect of Alizarin is achieved by activating VEGFR2/eNOS pathway, attenuating oxidative stress-induced mitochondrial damage and premature senescence.

ABSTRACT

The primary and initial manifestations of hypertension encompass arterial hypoelasticity and histiocyte senescence. Oxidative stress plays a pivotal role in the progression of senescence. Elevated intracellular oxidative stress levels will directly induce cell damage, disrupt normal physiological signal transduction, which can cause mitochondrial dysfunction to accelerate the process of senescence. Alizarin, an anthraquinone active ingredient isolated from Rubia cordifolia L., has a variety of pharmacological effects, including antioxidant, anti-inflammatory and anti-platelet. Nevertheless, its potential in lowering blood pressure (BP) and mitigating hypertension-induced vascular senescence remains uncertain. In this study, we used spontaneously hypertensive rats (SHR) and human umbilical vein endothelial cells (HUVECs) to establish a model of vascular senescence in hypertension. Our aim was to elucidate the mechanisms underpinning the vascular protective effects of Alizarin. By assessing systolic blood pressure (SBP) and diastolic blood pressure (DBP), H&E staining, SA-ß-Gal staining, vascular function, oxidative stress levels, calcium ion concentration and mitochondrial membrane potential, we found that Alizarin not only restored SBP and increased endothelium-dependent relaxation (EDR) in SHR, but also inhibited oxidative stress-induced mitochondrial damage and significantly delayed the vascular senescence effect in hypertension, and the mechanism may be related to the activation of VEGFR2/eNOS signaling pathway.