Molecular mechanism of phytochemical compounds in mitigating hypertension

• Phytochemicals help prevent hypertension by altering key signal transduction pathways. • Hypertension pathways involve VSMC, ROS, NO, RAS, NFκB, PGI2, and endothelial dysfunction. • Understanding molecular pathways helps researcher formulate safer, more effective treatments. • Targeted research on phytochemicals improves hypertension therapy while minimizing side effects. Hypertension is a leading risk factor for cardiovascular diseases and mortality worldwide, particularly in low- and middle-income countries. While conventional antihypertensive therapies exist, their adverse effects and cost limit accessibility, prompting the exploration of safer, plant-based alternatives. This review aims to comprehensively examine the therapeutic potential of phytochemicals in the management of hypertension by elucidating their mechanisms of action across multiple molecular pathways. A comprehensive literature review was conducted using databases including PubMed®, Google Scholar, ScienceDirect®, and Scopus. The analysis focused on phytochemicals affecting vascular smooth muscle cells (VSMCs), oxidative stress (ROS/NO), the renin–angiotensin system (RAS), NF-κB signaling, endothelial dysfunction, and prostacyclin (PGI₂) pathways. Numerous phytochemicals, including quercetin, resveratrol, apigenin, and ursolic acid, demonstrate antihypertensive effects by targeting key signaling cascades involved in vascular remodeling, inflammation, and oxidative stress. Emerging evidence supports the role of nanotechnology in enhancing their bioavailability and therapeutic efficacy. However, challenges remain regarding bioavailability, standardization, clinical validation, and potential drug interactions. Phytochemicals offer a multi-targeted and sustainable strategy for hypertension management. Future research should prioritize clinical trials, pharmacokinetics, personalized approaches, and advanced delivery systems to translate preclinical findings into clinical practice and improve outcomes in hypertensive populations.