Antioxidant Properties of Neohesperidin Dihydrochalcone: Inhibition of Hypochlorous Acid-Induced DNA Strand Breakage, Protein Degradation, and Cell Death

Abstract

Reactive oxygen species (ROS) and free radicals induce membrane damages, DNA strand breaks, and protein alterations. Oxidative stress, induced by oxygen radicals, is believed to be a primary factor in various degenerative diseases as well as in the normal process of aging. The ROS are involved in the course of aging, cancer, cardiovascular disease, diabetes, neurodegenerative disease, osteoporosis, etc. 1,2) Among the various reactive species, superoxide radical ( · O 2 Ϫ ), hydroxyl radical ( · OH), hydrogen peroxide (H 2 O 2 ), and hypochlorous acid (HOCl) play important roles in the pathophysiologies as mentioned above, which make them potential targets for the chemotherapy of inflammatory diseases. 3)Neohesperidin dihydrochalcone (NHDC) is an intense sweetener which is produced by hydrogenation of neohesperidin first prepared by Horowitz and Gentili in 1963. 4) Citrus fruits are rich sources of neohesperidin; the peels of oranges, lemons, and grapefruit contain bitter taste of neohesperidin. [5][6][7][8][9] Dihydrochalcones are a family of the bicyclic flavonoids, defined by the presence of two benzenoid rings joined by a three-carbon bridge. NHDC, the most familiar among these compounds, is permitted for commercial use as a food additive in Europe on the basis of its safety assessed by the EU Scientific Committee for Food. 10) In recent studies, there were several reports about improve the solubility and stability in aqueous solution and another research group evaluated neohesperidin-rich plant to get a source of NHDC. 8,11) Some dihydrochalcones including phloridzin and myrigalone B have been found to occur naturally 12,13) and to possess an antioxidant activity.14,15) Several chalcones inhibit various enzymes involved in the generation of reactive oxygen species and many of their pharmacological properties are supposed to be related to their antioxidant effect.16) Recently, 2Ј,5Ј-dihydroxychalcones have been reported as potent anti-inflammatory chemicals. 17,18) Although a large number of antioxidants, including most types of flavonoids, have been reported in the literature, there are few systematic studies of dihydrochalcones on biological activities such as an antioxidant effect. In recent studies, NHDC can inhibit DPPH stable radical, lipid peroxidation, and xanthine oxidase activity. 19,20) However, there are few reports to evaluate NHDC as an antioxidant or specific radical scavenger.In this study, to evaluate NHDC as a novel antioxidant material for a pharmaceutical agent or a food additive, its stable radical scavenging activity and inhibitory effect on the major inflammation-related ROS including · O 2 Ϫ , H 2 O 2 , · OH, and HOCl were elaborated. Also, the inhibitory effect of NHDC on protein degradation, DNA strand cleavage, and cellular damage from HOCl attack were determined to verify the specific ROS scavenging function. In addition, the ROS scavenging effect of the structurally related compounds including neohesperidin and phloridzin was also estimated to explore the structure-activity rel...

Antidiarrhoeal and intestinal modulatory activities of Wei-Chang-An-Wan extract

“…It is also reported that hesperidin was able to show improvement in the levels of endogenous antioxidant enzymes, give protection against the free radicals generation (Balakrishnan and Menon, 2007), terminate the lipid peroxidation side chain and provide strong cellular antioxidant protection against the damaging effects induced by peroxide hydrogen (Kalpana et al, 2009). Additionally, neohesperidin has been found to inhibit various enzymes involved in the generation of reactive oxygen species (Choi et al, 2007). Besides, naringin and hesperidin are known to be partly degraded in the gut to their aglycones naringenin and hesperetin, respectively, by intestinal microflora (Kim et al, 1998), and hesperetin was shown to be a more potent antioxidant than hesperidin, inhibiting generation of reactive oxygen species and lipid peroxidation (Cho, 2006).…”

Effects of UV-A LED light irradiation on growth of cultured RAW 264.7 cells

“…However, mannitol exerted little effect on inhibition (Figure 4). The antioxidant capacity value of mannitol to ROS is low (Choi et al 2007), and although mannitol abolished PDT-stimulated intracellular oxidative stress, PDT-induced apoptotic changes in cells were not affected (Chan and Wu 2004). One reason might be that mannitol is membrane-impermeable, and its scavenging ability against singlet oxygen is low because it is a scavenger of hydroxyl radicals (Li et al 2010).…”

Hydrogen Peroxide-Induced VCAM-1 Expression in Pancreatic Islets and β-Cells Through Extracellular Ca2+ Influx

“…The precise range of H 2 O 2 concentrations produced locally during inflammation under in vivo conditions is not known. Hence, we based our working concentrations from a survey of previously published relevant articles (20,(33)(34)(35)(36), which used H 2 O 2 concentrations in the range of 25 to 1000 M to activate rodent pancreatic islets and ␤-cell lines. Reactive oxygen species are a family of oxygen-derived free radicals produced in mammalian cells under normal and pathological conditions.…”