Cellular Defensive Mechanisms of Tea Polyphenols: Structure-Activity Relationship

Abstract

Tea is particularly rich in polyphenols, including catechins and theaflavins, thearubigins, flavonols, and phenolic acids, which are believed to contribute to the health benefits of tea. The health-promoting effects of tea polyphenols are believed to be related to their cellular defensive properties. This review is intended to briefly summarize the relationship between the chemical structures of tea polyphenols and their biological activities. Tea polyphenols appear as direct antioxidants by scavenging reactive oxygen/nitrogen species; chelating transition metals; and inhibiting lipid, protein, and DNA oxidations. They also act directly by suppressing "pro-oxidant" enzymes, inducing endogenous antioxidants, and cooperating with vitamins. Moreover, tea polyphenols regulate cellular signaling transduction pathways, importantly contributing to the prevention of chronic diseases and the promotion of physiological functions. Apparently, the features in the chemical structures of tea polyphenols are closely associated with their antioxidant potentials.

Keywords: black tea; cellular antioxidant defense; green tea; polyphenols; structure-activity relationship.

Figure 1

Chemical structures of major tea polyphenols.

Figure 2

Scheme showing ROS/RNS formation and possible antioxidant mechanisms of tea polyphenols. ROS/RNS can be produced by endogenous sources (e.g., mitochondria, xanthine oxidase, lipoxygenase, NADPH oxidase, cytochrome P450, and inducible nitric oxide synthase) and exogenous sources (e.g., ultraviolet light, polluted air, ionizing radiation, medications, and environmental toxicants). Under normal conditions, ROS/RNS are scavenged and neutralized by intracellular antioxidant defense systems, including enzymatic antioxidants (e.g., superoxide dismutase, catalase, glutathione peroxidase, and thioredoxin peroxidase) and nonenzymatic antioxidants (e.g., vitamin C and vitamin E). However, oxidative/nitrosative stress is associated with an overproduction of ROS/RNS that attacks cellular biomolecules such as proteins, lipids, and DNA, thereby resulting in the dysregulation of normal physiological functions and the onset of multiple chronic disorders such as cardiovascular diseases, inflammatory bowel diseases, and cancers. Tea polyphenols can inhibit ROS/RNS formation, scavenge and neutralize radicals and oxidants, upregulate intracellular antioxidant defense systems, and suppress oxidative/nitrosative biomolecule damages, thereby preventing the development of diseases. MPO, Myeloperoxidase; iNOS, Inducible nitric oxide synthase; O₂, oxygen; O₂•⁻, Superoxide anion; H₂O₂, Hydrogen peroxide; •OH, Hydroxyl radical; •NO, Nitric oxide; •NO₂, Nitrogen dioxide; ONOO⁻, Peroxynitrite; HClO, Hypochlorous acid; GSH, Glutathione; GSSG, Glutathione disulfide; Trx, Thioredoxin.

Figure 3

Cytoprotective mechanisms of tea polyphenols via regulation of phase I and phase II enzymes. Keap1, Kelch-like ECH-associated protein 1; maf, Musculoaponeurotic fibrosarcoma; Nrf2, Nuclear factor erythroid 2-related factor 2; HO-1, Heme oxygenase-1; NQO1, NADPH:quinone oxidoreductase 1; GST, Glutathione transferase; ERK, Extracellular signal-regulated kinase; JNK, c-Jun N-terminal kinase; UGTs, UDP-glucuronosyltransferases.

Figure 4

Cytoprotective mechanisms of tea polyphenols via regulation of inflammatory signaling pathways. AP-1, Activator protein 1; NF-κB, Nuclear factor kappa B; NEMO, NF-kappa-B essential modulator; STAT, Signal transducer and activator of transcription; ERK, Extracellular signal-regulated kinase; JNK, c-Jun N-terminal kinase; JAK, Janus kinases; IKKα/β, Inhibitor of nuclear factor Kappa-B kinase subunit alpha/beta; IκB, Inhibitor of κB; TAK1, Transforming growth factor-β-activated kinase 1; TLRs, Toll-like receptors; TNFR, Tumor necrosis factor receptor; IL-1R, Interleukin-1 receptor; IL-6R, Interleukin-6 receptor.