Kinetics of radical-scavenging activity of hesperetin and hesperidin and their inhibitory activity on COX-2 expression.
The radical-scavenging activities of the flavanones hesperetin and hesperidin were investigated by differential scanning calorimetry (DSC) monitoring of the polymerization of methyl methacrylate initiated by 2,2'-azobisisobutyronitrile (AIBN, an R* radical) or benzoylperoxide (BPO, a PhCOO* radical) at 70 degrees C under nearly anaerobic conditions. Their stoichiometric factor (number of free radicals trapped by one mole of antioxidant moiety (n)) and the ratio of the rate constant of inhibition to that of propagation (k(inh)/k(p)) were determined and compared with that for trolox The n value declined in the order trolox (2.0) > hesperetin (0.8) > hesperidin (0.2) in the AIBN system, whereas it declined in the order hesperetin (0.9) > trolox (0.1) > hesperidin (0.0) in the BPO system. The k(inh)/k(p) value declined in the order hesperidin (195) > hesperetin (33) > trolox (12) in the AIBN system, whereas it declined in the order hesperidin (362) > trolox (127) > hesperetin (18) in the BPO system. The n value of about 1 for hesperetin with a relatively small k(inh)/k(p) value suggests the formation of dimers, as a result of the coupling reaction of phenolic monomers. In contrast, n values << 1 for hesperidin and trolox in the BPO system resulted in very high values for k(inh)/k(p). Hesperidin was also much more able to suppress the growth of methyl methacrylate radicals, although its n value was small, suggesting that this compound may also suppress polyunsaturated fatty acid radicals. In the concentration range 250-500 microM, hesperetin and hesperidin showed potent inhibition of LPS-induced expression of the COX-2 gene in RAW 264.7 cells, suggesting the anti-inflammatory activity of these compounds. The ability of hesperetin and hesperidin to suppress COX-2 gene expression may be a consequence of their antioxidant activity.
Hirata
Atsusi
A
Department of Oral Diagnosis, Meikai University School of Dentistry, 350-0283 Saitama, Japan.
Murakami
Yukio
Y
Shoji
Masao
M
Kadoma
Yoshinori
Y
Fujisawa
Seiichiro
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D016718:Arachidonic Acid / Q000737:chemistry / Q000378:metabolism; D001585:Benzoyl Peroxide / Q000737:chemistry / Q000378:metabolism; D002152:Calorimetry, Differential Scanning; D002460:Cell Line; D002839:Chromans / Q000493:pharmacokinetics / Q000494:pharmacology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000493:pharmacokinetics / Q000494:pharmacology; D006569:Hesperidin / Q000493:pharmacokinetics* / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D009570:Nitriles / Q000737:chemistry / Q000378:metabolism; D044262:Prostaglandin H2 / Q000737:chemistry / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D002839:Chromans; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D009570:Nitriles; D016718:Arachidonic Acid; D044262:Prostaglandin H2; D006569:Hesperidin; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C004526:azobis(isobutyronitrile); C013015:hesperetin; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D001585:Benzoyl Peroxide