Chemical Study on Protective Effect Against Hydroxyl‐induced DNA Damage and Antioxidant Mechanism of Myricitrin

Excessive reactive oxygen species (ROS) can oxidatively damage DNA to cause severe biological consequences. In the study, a natural flavonoid, myricitrin (myricetin-3-O-α-L-rhamnopyranoside), was found to have a protective effect against hydroxyl-induced DNA damage (IC50 159.86 ± 54.24 μg/mL). To investigate the mechanism, it was determined by various antioxidant assays. The results revealed that myricitrin could effectively scavenge ·OH, ·O2−, DPPH· (1,1-diphenyl-2-picrylhydrazyl radical), and ABTS+· (2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radicals (IC50 values were respectively 69.71 ± 5.93, 69.71 ± 5.93, 25.34 ± 2.14, and 1.71 ± 0.09 μg/mL), and bind Cu2+ (IC50 27.33 ± 2.36 μg/mL). Based on the mechanistic analysis, it can be concluded that: (i) myricitrin can effectively protect against hydroxyl-induced DNA oxidative damage via ROS scavenging and deoxynucleotide radicals repairing approaches. Both approaches can be attributed to its antioxidant. From a structure-activity relationship viewpoint, its antioxidant ability can be attributed to the ortho-dihydroxyl moiety, and ultimately to the stability of its oxidized form ortho-benzoquinone; (ii) its ROS scavenging is mediated via metal-chelating, and direct radical-scavenging which is through donating hydrogen (H·) and electron (e); and (iii) its protective effect against DNA oxidative damage may be primarily responsible for the pharmacological effects, and offers promise as a new therapeutic reagent for diseases from DNA oxidative damage.

[1]  E. Lissi,et al.  Reaction of 2,2′-azinobis 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) derived radicals with hydroperoxides. Kinetics and mechanism , 1998 .

[2]  Xican Li Solvent effects and improvements in the deoxyribose degradation assay for hydroxyl radical-scavenging. , 2013, Food chemistry.

[3]  Dimitrios Tsimogiannis,et al.  The contribution of flavonoid C-ring on the DPPH free radical scavenging efficiency. A kinetic approach for the 3′,4′-hydroxy substituted members , 2006 .

[4]  S. Tannenbaum,et al.  Infection-induced colitis in mice causes dynamic and tissue-specific changes in stress response and DNA damage leading to colon cancer , 2012, Proceedings of the National Academy of Sciences.

[5]  Xican Li Improved pyrogallol autoxidation method: a reliable and cheap superoxide-scavenging assay suitable for all antioxidants. , 2012, Journal of agricultural and food chemistry.

[6]  R. Apak,et al.  A novel hydrogen peroxide scavenging assay of phenolics and flavonoids using cupric reducing antioxidant capacity (CUPRAC) methodology , 2010 .

[7]  S. Yao,et al.  Fast repair of deoxynucleotide radical cations by phenylpropanoid glycosides (PPGs) and their analogs. , 1999, Biochimica et biophysica acta.

[8]  H. Corke,et al.  Structure-radical scavenging activity relationships of phenolic compounds from traditional Chinese medicinal plants. , 2006, Life sciences.

[9]  C. Berset,et al.  Kinetics and Mechanisms of Antioxidant Activity using the DPPH.Free Radical Method , 1997 .

[10]  Dongfeng Chen,et al.  Antioxidant Ability and Mechanism of Rhizoma Atractylodes macrocephala , 2012, Molecules.

[11]  Xingqian Ye,et al.  Inhibition effects and induction of apoptosis of flavonoids on the prostate cancer cell line PC-3 in vitro. , 2013, Food chemistry.

[12]  S. Bonora,et al.  Copper(II)–Quercetin complexes in aqueous solutions: spectroscopic and kinetic properties , 2005 .

[13]  H. Esterbauer,et al.  Hydroxyl-radical-induced iron-catalysed degradation of 2-deoxyribose. Quantitative determination of malondialdehyde. , 1988, The Biochemical journal.

[14]  H. Tamura,et al.  Isolation of bilberry anthocyanidin 3-glycosides bearing ortho-dihydroxyl groups on the B ring by forming an aluminum complex and their antioxidant activity. , 2012, Journal of agricultural and food chemistry.

[15]  Xican Li,et al.  Correlation between Antioxidant Activities and Phenolic Contents of Radix Angelicae Sinensis (Danggui) , 2009, Molecules.

[16]  Kelly E Heim,et al.  Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. , 2002, The Journal of nutritional biochemistry.

[17]  P. Cerutti Prooxidant states and tumor promotion. , 1985, Science.

[18]  H. L. Wright,et al.  Neutrophil function in inflammation and inflammatory diseases. , 2010, Rheumatology.

[19]  E. Jaimes,et al.  Mitochondria and Reactive Oxygen Species: Physiology and Pathophysiology , 2013, International journal of molecular sciences.

[20]  Dongfeng Chen,et al.  Antioxidant activity and mechanism of Rhizoma Cimicifugae , 2012, Chemistry Central Journal.

[21]  D. Jerina,et al.  Inhibition of the mutagenicity of bay-region diol-epoxides of polycyclic aromatic hydrocarbons by phenolic plant flavonoids. , 1983, Carcinogenesis.

[22]  A. Kettle,et al.  Myricitrin as a substrate and inhibitor of myeloperoxidase: implications for the pharmacological effects of flavonoids. , 2008, Free radical biology & medicine.

[23]  B. Van Houten,et al.  Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[24]  M. Heidari,et al.  Synthesis and antioxidant properties of substituted 3-benzylidene-7-alkoxychroman-4-ones. , 2007, Bioorganic & medicinal chemistry letters.

[25]  A. Abdel-Naim,et al.  Anti-inflammatory activity of Pistacia khinjuk in different experimental models: isolation and characterization of its flavonoids and galloylated sugars. , 2012, Journal of medicinal food.

[26]  M. Dizdaroglu,et al.  Free radical-induced damage to DNA: mechanisms and measurement. , 2002, Free radical biology & medicine.

[27]  C. A. de Paula,et al.  Anti-inflammatory and antinociceptive activities of Campomanesia adamantium. , 2013, Journal of ethnopharmacology.