Mechanistic role of natural products in reducing arsenic toxicity and ameliorating human health: a sustainable approach for managing arsenic toxicity

Abstract

Arsenic contamination of drinking water, food, and environmental components remains a major global health concern because chronic exposure to inorganic arsenic is associated with multisystem toxicity and carcinogenesis. Arsenic-induced toxicity includes a complex interaction of pathways including oxidative and thiol stress, mitochondrial dysfunction, inflammatory signaling, DNA damage, epigenetic dysregulation and altered apoptotic responses. This study critically reviews the potential benefits of plant-derived phytochemicals and medicinal-plant formulations to mitigate arsenic toxicity, focusing on their molecular processes, empirical information, and translational significance. Polyphenols, flavonoids, organosulfur compounds, carotenoids and other bioactive constituents have demonstrated protective effects mainly in cellular and animal models through the modulation of antioxidant defense, glutathione homeostasis, NRF2/ARE and NF-κB/MAPK signaling, mitochondrial function, inflammation and apoptosis. Some bioactive compounds and phytochemical–chelator combinations have been proven to interact directly with arsenic, modify arsenic disposition, or improve elimination; however, this observation does not apply to all phytochemicals. Limited human evidence provides preliminary translational support, although clinical efficacy remains insufficiently established. Complementary efforts to reduce arsenic exposure through agricultural management, molecular breeding and plant-based environmental remediation are also examined. Major translational challenges are low or variable bioavailability, lack of dosage standardization, insufficient pharmacokinetic data, possible herb-drug interactions, and a lack of controlled clinical studies. This review highlights the phytochemicals represent a promising complementary approach to mitigate arsenic-induced cellular and tissue damage. However, additional mechanistic validation, standardized formulations, safety assessment, and well-designed human studies are needed before their clinical application.