Chemical Study on Protective Effect Against Hydroxyl- induced DNA Damage and Antioxidant Mechanism of Myricitrin
Chemical Study on Protective Effect Against Hydroxyl- induced DNA Damage and Antioxidant Mechanism of Myricitrin
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DOI：
10.1002/jccs.201300396
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发表时间：
2014-03-01
影响因子：
1.8
通讯作者：
Chen, Dongfeng
中科院分区：
文献类型：
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作者：
Li, Xican;Mai, Wenqiong;Chen, Dongfeng
过量的活性氧(ROS)会对DNA造成氧化损伤，造成严重的生物后果。研究发现，天然黄酮类化合物杨梅素(杨梅素-3-O-α-L-鼠李糖苷)对羟基诱导的DNA损伤有保护作用(IC_(50)为159.86+/-54.24mU/mL)。为探讨其作用机制，采用多种抗氧化剂测定其抗氧化活性。结果表明，杨梅素能有效清除中心点OH、中心点O-2(-)、DPPH中心点(1，1-二苯基-2-苦基肼自由基)和ABTS(+)中心点(2，2‘-Azino-bis(3-ethylbenzothiazoline-6-sulfonic酸自由基(IC50值分别为69.71+/-5.93、69.71+/-5.93、25.34+/-2.14和1.71+/-0.09mU/mL)，并结合Cu2+(IC5027.33+/-2.36mU/mL)。根据机理分析，可以得出结论：(1)杨梅苷通过清除ROS和脱氧核苷酸修复途径，有效地对抗羟基诱导的DNA氧化损伤。这两种方法都可以归因于它的抗氧化剂。从构效关系的角度来看，其抗氧化能力可归因于邻二羟基，并最终归因于其氧化形式邻苯二酚的稳定性；(Ii)其清除ROS是通过金属螯合，并通过供氢(H中心点)和电子(E)直接清除自由基；以及(Iii)其对DNA氧化损伤的保护作用可能是其药理作用的主要机制，有望成为治疗DNA氧化损伤疾病的新药物。
Excessive reactive oxygen species (ROS) can oxidatively damage DNA to cause severe biological consequences. In the study, a natural flavonoid, myricitrin (myricetin-3-O-alpha-L-rhamnopyranoside), was found to have a protective effect against hydroxyl-induced DNA damage (IC50 159.86 +/- 54.24 mu g/mL). To investigate the mechanism, it was determined by various antioxidant assays. The results revealed that myricitrin could effectively scavenge center dot OH, center dot O-2(-), DPPH center dot (1,1-diphenyl-2-picrylhydrazyl radical), and ABTS(+)center dot (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 mu g/mL), and bind Cu2+ (IC50 27.33 +/- 2.36 mu g/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 center dot) 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.