Plant Polyphenols as a Double-Edged Sword in Health Promotion: Lessons from the Experimental Models Using Simple Phenolic Acids

Abstract

erized molecules such as tannins are reportedly identified. Phenolic acids include caffeic acid, vanillic acid, and coumaric acid, that account for approximately onethird of the total dietary intake of polyphenols. Flavonoids, account for the remaining two-thirds of polyphenol intake, can be further subdivided into 13 classes, including flavones, flavanones, flavonols, isoflavones, catechins (flavanols), anthocyanins and proanthocyanidins, with more than 5,000 identified compounds. Epidemiological studies have supported the hypothesis that high dietary intake of polyphenols is associated with decreased risk of a range of diseases including cardiovascular disease, cancer and neurodegenerative diseases (Fraga 2007;Martin and Appel 2010). Since the French paradox was described two decades ago (Renaud and Lorgeril 1992), several Abstract Polyphenols in foods possess potential to exhibit various beneficial effects in health promotion. Although polyphenols are well known to have antioxidant properties, a wealth of data suggests that most of the relevant mechanisms of disease prevention by polyphenols are not mainly related to their antioxidant properties. The protective function of phenolic compounds, which can be metabolically converted into electrophiles, might be ascribed to the induction of the cytoprotective responses against oxidative stress or toxic chemicals. Based on compelling evidence regarding the beneficial potential of polyphenols, various polyphenol-rich dietary supplements are being developed for public use. It is recently becoming apparent that commonly used dietary compounds can exert deleterious effects at pharmacological (supraphysiological) doses. Moreover, some human intervention trials showed not only failure to protect by polyphenols but accelerated development of chronic diseases in susceptible subjects. Thus, the present monograph tries to provide experimental evidence supporting the idea that optimal polyphenol supplementation can confer beneficial effects but high doses elicit adverse effects in an electrophilic reaction-dependent manner, thereby establishing a double-edge sword in health promotion. Current knowledge of polyphenols as phase II inducers is also discussed, with consideration of the metabolic activation, binding targets and factors influencing the biological activities of polyphenols. In addition, this monograph attempts to provide a brief perspective on the beneficial and harmful effects of food polyphenols. Fig. 1. The major reactions of a catechol type-polyphenol; antioxidant, pro-oxidant, and electrophilic conjugation reactions. Reprinted from Bioscience, Biotechnology and Bioscience, 74(2), Nakamura and Miyoshi, Electrophiles in foods: the current status of isothiocyanates and their chemical biology, 242-255, Fig. 2. Conceptual illustration of electrophile and nucleophile. Reprinted from Bioscience, Biotechnology and Bioscience, 74(2), Nakamura and Miyoshi, Electrophiles in foods: the current status of isothiocyanates and their chemical biology, 242-255,

(−)-Epigallocatechin-3-gallate inhibits human angiotensin-converting enzyme activity through an autoxidation-dependent mechanism

“…EGCg has been reported to easily undergo autoxidation at alkaline pH, which is accompanied by the generation of hydrogen peroxide . As shown in Figure A, 10 μM of EGCg, which completely inhibited the ACE activity (Figure B), produced 16.1 μM of hydrogen peroxide during a 30‐min incubation.…”

“…EGCg has been reported to easily undergo autoxidation at alkaline pH, which is accompanied by the generation of hydrogen peroxide. [14,18] As shown in Figure 3A…”

“…Therefore, the chelation of Zn 2+ at the active site of ACE seems to be one of the possible mechanisms for tea catechins to inhibit ACE activity. Other plausible mechanisms can be postulated; that is, the autoxidation of polyphenols with a catechol structure leads to the formation of their quinones and reactive oxygen species, both of which can modify the amino acid residues in proteins through covalent conjugation and oxidation, respectively . Although both the iron chelation and direct protein modification might be involved in the ACE inhibition by tea catechins, the precise mechanism remains to be clarified.…”

Physiological relevance of covalent protein modification by dietary isothiocyanates

“…( 1 ) For example, both BITC and PEITC promote urinary bladder chemical carcinogenesis in rats, possibly through necrotic cytotoxicity by severe protein modification. ( 87 ) Our previous studies on the toxic effects of higher doses of phenolic acids ( 88 ) also support this idea. If the dose employed is higher than that required for health promotion, the benefitial effects of ITCs might not be entirely expected.…”

Protective Effects of a Strawberry Ellagitannin-Rich Extract against Pro-Oxidative and Pro-Inflammatory Dysfunctions Induced by a High-Fat Diet in a Rat Model

“…Research reported that dietary polyphenols may activate AMPK (AMP-activated protein kinase) via SIRT1 and LKB1, thus inhibiting ACC activity and decreasing the production of malonyl-CoA. As a result, FA β-oxidation is upregulated along with downregulated FA synthesis, thereby leading to hepatocyte lipid reduction [ 36 ]. In the present experiment, the dietary strawberry extract, irrespective of the dosage, exerted similar antioxidative and anti-inflammatory effects in the liver and plasma of rats fed an HFD.…”