Tapping into Nature's Arsenal: Harnessing the Potential of Natural Antioxidants for Human Health and Disease Prevention

Abstract

Numerous natural antioxidants commonly found in our daily diet have demonstrated significant benefits for human health and various diseases by counteracting the impact of reactive oxygen and nitrogen species. Their chemical properties enable a range of biological actions, including antihypertensive, antimicrobial, anti-inflammatory, anti-fibrotic, and anticancer effects. Despite promising outcomes from preclinical studies, ongoing debate persists regarding their reproducibility in human clinical models. This controversy largely stems from a lack of understanding of the pharmacokinetic properties of these compounds, coupled with the predominant focus on monotherapies in research, neglecting potential synergistic effects arising from combining different antioxidants. This study aims to provide an updated overview of natural antioxidants, operating under the hypothesis that a multitherapeutic approach surpasses monotherapy in efficacy. Additionally, this study underscores the importance of integrating these antioxidants into the daily diet, as they have the potential to prevent the onset and progression of various diseases. To reinforce this perspective, clinical findings pertaining to the treatment and prevention of non-alcoholic fatty liver disease and conditions associated with ischemia and reperfusion phenomena, including myocardial infarction, postoperative atrial fibrillation, and stroke, are presented as key references.

Keywords: ischemia–reperfusion injury; natural antioxidants; non-alcoholic fatty liver disease; oxidative stress; polyphenols; protective mechanisms; vitamins.

Figure 1

Basic cellular mechanisms of defense against oxidative stress. SOD, superoxide dismutase. CAT, catalase. GPX, glutathione peroxidase. TRX, thioredoxin.

Figure 2

Inter-related molecular mechanisms through which natural antioxidants exert their antioxidant effects. AKT, protein kinase B; AMPK, AMP-activated protein kinase; Fe²⁺, ferrous iron; Fe³⁺, ferric iron; Keap1, Kelch-like ECH associated protein 1; Nrf-2, nuclear factor-erythroid 2-related factor 2; PI3K, phosphoinositide 3-kinase; PIP3, phosphatidylinositol (3,4,5)-triphosphate; PUFAs, polyunsaturated fats; ROS, reactive oxygen species; SIRT-1, sirtuin 1; SOD, superoxide dismutase; TRX, thioredoxin.

Figure 3

Mechanisms of action of natural antioxidants on ischemia and reperfusion injury in acute myocardial infarction. Blue upward arrows (↑) indicate upregulation. ARE, antioxidant response element; AST, astaxanthin; CAT, catalase; DHA, dehydroascorbic acid; Fe³⁺, ferric iron; Fe²⁺, ferrous iron; GPX, glutathione peroxidase; GSH, reduced glutathione; GSSG, oxidized glutathione; GST, glutathione transferase; HO-1, heme oxygenase-1; IκB, NF-κB inhibitor protein; KEAP1, Kelch-like ECH-associated protein 1; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; Nrf2, nuclear factor-erythroid 2-related factor 2; NOX, reduced nicotinamide adenine dinucleotide phosphate oxidase; SOD, superoxide dismutase; Tf, transferrin; TfR1, transferrin receptor protein 1; Vit C, vitamin C; Vit E, vitamin E; XO, xanthine oxidase.