Paradigm Shift in Phytochemicals Research: Evolution from Antioxidant Capacity to Anti-Inflammatory Effect and to Roles in Gut Health and Metabolic Syndrome

Abstract

Food bioactive components, particularly phytochemicals with antioxidant capacity, have been extensively studied over the past two decades. However, as new analytical and molecular biological tools advance, antioxidants related research has undergone significant paradigm shifts. This review is a high-level overview of the evolution of phytochemical antioxidants research. Early research used chemical models to assess the antioxidant capacity of different phytochemicals, which provided important information about the health potential, but the results were overused and misinterpreted despite the lack of biological relevance (Antioxidants v1.0). This led to findings in the anti-inflammatory properties and modulatory effects of cell signaling of phytochemicals (Antioxidants v2.0). Recent advances in the role of diet in modulating gut microbiota have suggested a new phase of food bioactives research along the phytochemicals−gut microbiota−intestinal metabolites−low-grade inflammation−metabolic syndrome axis (Antioxidants v3.0). Polyphenols and carotenoids were discussed in-depth, and future research directions were also provided.

Rice Protein Peptides Alleviate Dextran Sulfate Sodium-Induced Colitis via the Keap1–Nrf2 Signaling Pathway and Regulating Gut Microbiota

“…Oxidative stress may affect inflammatory signaling pathways, including Keap1–Nrf2, and aggravate inflammation . The occurrence and aggravation of inflammation is a complex process, which is closely related to the pathogen activation of macrophages.…”

“…Oxidative stress may affect inflammatory signaling pathways, including Keap1−Nrf2, and aggravate inflammation. 38 The occurrence and aggravation of inflammation is a complex process, which is closely related to the pathogen activation of macrophages. Activated macrophages will produce cytokines, such as tumor necrosis factor-α (TNF-α) interleukins (IL-6, IL-8), 39 and are considered to be key to triggering inflammations.…”

Flavonoids Are Intra- and Inter-Kingdom Modulator Signals

“…Flavonoids and their metabolites can improve human health by acting as phytochemicals [241], nonessential molecules consumed through food or dietary complements, that modulate signaling pathways and decrease inflammation, immune response and oxidative stress processes [43]. This review will treat this topic highlighting flavonoids' role as inter-kingdom signaling molecules also in the context of human pathologies: other works have dedicated valuable efforts to elucidate the medical and nutraceutical potential of these compounds [41,[242][243][244][245][246].…”

“…Flavonoids were shown to exert a variety of nutraceutical features such as antioxidative, anti-diabetic, anti-proliferative, anti-carcinogenic, anti-microbial and immunomodulatory abilities [44]. Due to these abilities, flavonoid supplements have been largely investigated in studies for prevention or drug efficacy evaluation in several pathologies including cancer, atherosclerosis, stroke, neuroinflammatory diseases, age-related neurodegeneration, diabetes, human herpes virus (HHV) infections and recently also COVID-19 respiratory disease [43,60,247,248] (Figure 2). Interestingly, one of the main effects of these illnesses is oxidative stress, which induces harmful damages on membranes, lipids, proteins, lipoproteins and DNA in humans [249], similar to the dangerous effects previously described in plants.…”

“…Interestingly, one of the main effects of these illnesses is oxidative stress, which induces harmful damages on membranes, lipids, proteins, lipoproteins and DNA in humans [249], similar to the dangerous effects previously described in plants. The role of flavonoids as conventional hydrogen-donating antioxidants has been extensively reviewed and leads to a paradigm shift in their acknowledged functions in human disorders [43]. According to an emerging scenario, these phytochemicals may exert their beneficial activities in human health mainly by interfering with signaling pathways [242].…”