Medicinal Plants That Modulate Nitric Oxide Synthase Activity: Implications in Inflammation and Oxidative Stress

Nitric oxide (NO) plays a central role in diverse physiological processes, such as cardiovascular tone, neurotransmission, immune defense, and cellular apoptosis. NO synthase (NOS) is the enzyme that catalyzes the conversion of L-arginine to L-citrulline and NO. Three isoforms of NOS are (1) neuronal NOS (nNOS), which regulates synaptic plasticity, memory formation, and cerebral blood flow, (2) endothelial NOS (eNOS), which supports cardiovascular homeostasis by preventing platelet aggregation and leukocyte adhesion, and (3) inducible NOS (iNOS), which contributes to inflammation and tissue damage, when in excessive production. Thus, targeting iNOS without interfering with the beneficial actions of nNOS and eNOS remains a major therapeutic challenge. Given this dual nature of NO in health and disease, it is important to understand how medicinal plants and their phytochemicals modulate NO pathways. A systematic search of Scopus and PubMed databases was performed for studies published in the last ten years. Screening by title, abstract, and full text yielded 35 eligible articles examining medicinal plants and phytochemicals that influence NO signaling pathways. Preclinical evidence indicates that phytochemicals restore antioxidant defenses and suppress excessive NO and oxidative stress under inflammatory conditions while preserving or enhancing endothelial NO bioavailability. Emerging clinical findings further suggest significantly greater insulin-stimulated NO production and eNOS activation without activating iNOS or promoting inflammatory responses. Their ability to regulate NO production underscores their potential in the development of botanical drugs targeting iNOS while preserving the physiological roles of nNOS and eNOS. This review provides an overview of the potential of medicinal plants to alleviate inflammation and oxidative stress through modulation of NO production.