Protective effects of pomegranate (Punica granatum) and its main components against natural and chemical toxic agents: A comprehensive review

Background: Different chemical toxicants or natural toxins can damage human health through various routes such as air, water, fruits, foods, and vegetables. Purpose: Herbal medicines may be safe and selective for the prevention of toxic agents due to their active in-gredients and various pharmacological properties. According to the beneficial properties of pomegranate, this paper summarized the protective effects of this plant against toxic substances. Study design: In this review, we focused on the findings of in vivo and in vitro studies of the protective effects of pomegranate (Punica granatum) and its active components including ellagic acid and punicalagin, against natural and chemical toxic agents. Methods: We collected articles from the following databases or search engines such as Web of Sciences, Google Scholar, Pubmed and Scopus without a time limit until the end of September 2022. Results: P. granatum and its constituents have shown protective effects against natural toxins such as aflatoxins, and endotoxins as well as chemical toxicants for instance arsenic, diazinon, and carbon tetrachloride. The protective effects of these compounds are related to different mechanisms such as the prevention of oxidative stress, and reduction of inflammatory mediators including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), cyclooxygenase-2(COX-2) and nuclear factor kappa B (NF-kappa B) as well as the modulation of apoptosis, mitogen-activated protein kinase (MAPK) signaling pathways and improvement of liver or cardiac function via regulation of enzymes. Conclusion: In this review, different in vitro and in vivo studies have shown that P. granatum and its active constituents have protective effects against natural and chemical toxic agents via different mechanisms. There are no clinical trials on the protective effects of P. granatum against toxic agents.