Nrf2 activators counteract oxidative stress: an update

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DENG Hui-yan(Guangzhou Institute of Dermatology, Guangzhou 510095, China)
ZHU Hui-lan(Guangzhou Institute of Dermatology, Guangzhou 510095, China)
Journal Title:
International Journal of Dermatology and Venereology
Volume 38, Issue 05, 2012
Key Word:
Nrf2 activator; Antioxidants; EGCG; Curcumin; Sulforaphane

Abstract: Ultraviolet radiation can not only induces acute and chronic inflammation in skin,but also trigger oxidative stress response tollowed by the production of reactive oxygen species (ROS).The Nrf2-Keapl system can counteract ROS via regulating the expression of protective genes in cells.As Nrf2 activators,natural antioxidants,such as (-)-epigallocatechin-3-gallate (EGCG),curcumin and sulforaphane counteract oxidative stress by directly scavenging free radicals or indirectly increasing endogenous cellular antioxidant defenses.In detail,these activators may activate Nrf2 by binding to Nrf2 or Keap1 with different chemical structures followed by alteration of configurations,which in turn initiates anti-oxidative stress response to counteract ultraviolet-induced oxidative stress.

  • [1]Kawachi Y,Xu X,Taguchi S,et al.Attenuation of UVB-induced sunburn reaction and oxidative DNA damage with no alterations in UVB-induced skin carcinogenesis in Nrf2 gene-deficient mice.J Invest Dermatol,2008,128(7):1773-1779.
  • [2]Wondrak GT,Cabello CM,Villeneuve NF,et al.Cinnamoyl-based Nff2-activators targeting human skin cell photo-oxidative stress.Free Radic Biol Med,2008,45(4):385-395.
  • [3]Saw CL,Huang MT,Liu Y,et al.Impact of Nrf2 on UVB-induced skin inflammation/photoprotection and photoprotective effect of sulforaphane.Mol Carcinog,2011,50(6):479-486.
  • [4]Scapagnini G,Vasto S,Abraham NG,et al.Modulation of Nrf2/ARE pathway by food polyphenols:a nutritional neuroprotective strategy for cognitive and neurodegenerative disorders.Mol Neurobiol,2011,44(2):192-201.
  • [5]高爱莉,朱慧兰.Nrf2-Keap1系统防御紫外线所致皮肤光损伤的研究进展.国际皮肤性病学杂志,2011:37(5):61-63.
  • [6]Dinkova-Kostova AT,Holtzclaw WD,Cole RN,et al.Direct evidence that sulfhydryl groups of Keapl are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants.Proc Natl Acad Sci U S A,2002,99 (18):11908-11913.
  • [7]Marrot L,Jones C,Perez P,et al.The significance of Nrf2 pathway in (photo)-oxidative stress response in melanocytes and keratinocytes of the human epidermis.Pigment Cell Melanoma Res,2008,21(1):79-88.
  • [8]Kelsey NA,Wilkins HM,Linseman DA.Nutraceutical antioxidants as novel neuroprotective agents.Molecules,2010,15 (11):7792-7814.
  • [9]Tsai PY,Ka SM,Chang JM,et al.Epigallocatechin-3-gallate prevents lupus nephritis development in mice via enhancing the Nrf2 antioxidant pathway and inhibiting NLRP3 inflammasome activation.Free Radic Biol Med,2011,51 (3):744-754.
  • [10]Rahman I,Biswas SK,Kirkham PA.Regulation of inflammation and redox signaling by dietary polyphenols.Biochem Pharmacol,2006,72(11):1439-1452.
  • [11]Na HK,Surh YJ.Modulation of Nrf2-mediated antioxidant anddetoxifying enzyme induction by the green tea polyphenol EGCG.Food Chem Toxicol,2008,46(4):1271-1278.
  • [12]Goel A,Aggarwal BB.Curcumin,the golden spice from Indian saffron,is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for norml organs.Nutr Cancer,2010,62(7):919-930.
  • [13]Demirovic D,Rattan SI.Curcumin induces stress response and hormetically modulates wound healing ability of human skin fibroblasts undergoing ageing in vitro.Biogerontology,2011,12(5):437-444.
  • [14]Hatcher H,Planalp R,Cho J,et al.Curcumin:from ancient medicine to current clinical trials.Cell Mol Life Sci,2008,65(11):1631-1652.
  • [15]Khor TO,Huang Y,Wu TY,et al.Pharmacodynamics of curcumin as DNA hypomethylation agent in restoring the expression of Nrf2 via promoter CpGs demethylation.Biochem Pharmacol,2011,82(9):1073-1078.
  • [16]Ahn YH,Hwang Y,Liu H,et al.Electrophilic tuning of the chemoprotective natural product sulforaphane.Proc Natl Acad Sci U S A,2010,107(21):9590-9595.
  • [17]Dinkova-Kostova AT.Phytochemicals as protectors against ultraviolet radiation:versatility of effects and mechanisms.Planta Med,2008,74(13):1548-1559.
  • [18]Kerns M,DePianto D,Yamamoto M,et al.Differential modulation of keratin expression by sulforaphane occurs via Nrf2-dependent and-independent pathways in skin epithelia.Mol Biol Cell,2010,21 (23):4068-4075.
  • [19]Wagner AE,Ernst I,Iori R,et al.Sulforaphane but not ascorbigen,indole-3-carbinole and ascorbic acid activates the transcription factor Nrf2 and induces phase-2 and antioxidant enzymes in human keratinocytes in culture.Exp Dermatol,2010,19(2):137-144.
  • [20]Dickinson SE,Melton TF,Olson ER,et al.Inhibition of activator protein-1 by sulforaphane involves interaction with cysteine in the cFos DNA-binding domain:implications for chemoprevention of UVB-induced skin cancer.Cancer Res,2009,69 (17):7103-7110.
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