Research progress on the regulation of oxidative stress by phenolics: the role of gut microbiota and Nrf2 signaling pathway

Abstract

In recent years, the increase in high-calorie diets and sedentary lifestyles has made obesity a global public health problem. An unbalanced diet promotes the production of proinflammatory cytokines and causes redox imbalance in the body. Phenolics have potent antioxidant activity and cytoprotective ability. They can scavenge free radicals and reactive oxygen species, and enhance the activity of antioxidant enzymes, thus combating the body´s oxidative stress. They can also improve the body´s inflammatory response, enhance the enzyme activity of lipid metabolism, and reduce the contents of cholesterol and triglyceride. Most phenolics are biotransformed and absorbed into the blood after the action by gut microbiota; these metabolites then undergo phase I and II metabolism and regulate oxidative stress by scavenging free radicals and increasing expression of antioxidant enzymes. Phenolics induce the expression of genes encoding antioxidant enzymes and phase II detoxification enzymes by stimulating Nrf2 to enter the nucleus and bind to the antioxidant response element after uncoupling from Keap1, thereby promoting the production of antioxidant enzymes and phase II detoxification enzymes. The absorption rate of phenolics in the small intestine is extremely low. Most phenolics reach the colon, where they interact with the microbiota and undergo a series of metabolism. Their metabolites will reach the liver via the portal vein and undergo conjugation reactions. Subsequently, the metabolites reach the whole body to exert biological activity by traveling with the systemic circulation. Phenolics can promote the growth of probiotics, reduce the ratio of Firmicutes/Bacteroidetes (F/B), and improve intestinal microecological imbalance. This paper reviews the nutritional value, bioactivity, and antioxidant mechanism of phenolics in the body, aiming to provide a scientific basis for the development and utilization of natural antioxidants and provide a reference for elucidating the mechanism of action of phenolics for regulating oxidative stress in the body.