Apigenin and Hypertension: A Review of Natural Sources, Pharmacodynamic and Pharmacokinetic Evidence.

PURPOSE: This review aimed to synthesize recent evidence on the pharmacological effects of APG in the management of hypertension. METHODS: A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar. RESULTS: Pharmacokinetic studies reveal that APG exhibits poor oral bioavailability due to low solubility and extensive metabolism yet demonstrates wide tissue distribution and neuroprotective potential. It interacts with drug-metabolizing enzymes and transporters, influencing the pharmacokinetics of co-administered agents while maintaining a favorable safety profile at dietary levels. Preclinical evidence shows that APG lowers blood pressure by promoting vasodilation through TRPV4/NO pathways, attenuating oxidative stress and inflammation, and regulating genetic signaling to prevent vascular and cardiac remodeling. Toxicity studies confirm safety up to 5000 mg/kg, while additional findings highlight its beneficial modulation of gut microbiota. CONCLUSION: APG emerges as a promising supplementary compound for hypertension management, combining vascular, molecular, and microbiome-mediated mechanisms with a strong safety margin.