Oxidative stress and inflammation caused by n-Hexyl salicylate in mouse skin: the effectiveness of flavonoids


  • Nada Orsolic Department of Animal Physiology, Faculty of Science, University of Zagreb, Zagreb, Croatia.
  • Vedran Balta Department of Animal Physiology, Faculty of Science, University of Zagreb, Zagreb, Croatia.
  • Dyana Odeh Department of Animal Physiology, Faculty of Science, University of Zagreb, Zagreb, Croatia.
  • Maja Mataković Department of Animal Physiology, Faculty of Science, University of Zagreb, Zagreb, Croatia.
  • Jadranka Skurić Clinic of Anaesthesia and Intensive Care Unit, Sveti Duh General Hospital, Zagreb, Croatia


Flavonoids, Mice, n-Hexyl salicylate, oxidative stress, Skin inflammation


Reactive oxygen species (ROS) play a role in a numbered of degenerative conditions including psoriasis. Psoriasis is a chronic inflammatory disease who’s the etiopathogenesis is not yet completely understood, and therefore there is no standardized therapeutical approach. Flavonoids, recognized as potent antioxidants, are multifunctional molecules that can act as anti-inflammatory and antiproliferative agents through the modulation of multiple signaling pathways. The present study was designed to investigate the protective role of flavonoids [quercetin, chrysin, curcumin or Epigallocatechin 3-gallate (EGCG)] against n-Hexyl salicylate (HXS)-induced oxidative stress and inflammation in skin. Anti-oxidative and anti-inflammatory effect of flavonoids is quantified by histopathological assessment of skin, measuring the levels of lipid peroxidation and glutathione (GSH) in the skin, total number of inflammatory cells in peritoneal cavity, macrophage spreading index, and hematological and biochemical parameters. Topically applied of n-Hexyl salicylate caused significant increase in lipid peroxidation and decrease in GSH, which is accompanied by an increase total number of inflammatory cells in skin and peritoneal cavity, functional activity of macrophages, and enzymatic activity of ALP and AST. In contrast, topically applied 5 % preparation of flavonoids (quercetin, chrysin, curcumin or EGCG) with HXS effectively prevented these alterations and maintained the antioxidant status. The results suggest that flavonoid preparations can serve as a potent antioxidant and anti-inflammatory agents in psoriatic-like skin lesions, without toxic effects.


. Proksch E, Brandner JM, Jensen J-M. The skin: an indispensable barrier. Exp Dermatol 2008; 17: 1063–1072.

. De Benedictis C, Joubeh S, Zhang G, Barria M, Ghohestani RF. Immune functions of the skin. Clin Dermatol 2001; 19: 573–585.

. Pietrovski EF, Magina MD, Gomig F et al. Topical antiinflammatory activity of Eugenia brasiliensis Lam. (Myrtaceae) leaves. JPP 2008; 60: 479–487.

. Schön WP, Boencke WH. Psoriasis. N Engl J Med 2005; 352: 1899-912.

. Conrad C, Boyman O, Tonel G, Tun-Kyi A, Laggner U, et al. Alpha1beta1 integrin is crucial for accumulation of epidermal T cells and the development of psoriasis. Nat Med 2007; 13: 836–842.

. Pelle E, Mammone T, Maes D, Frenkel K. Keratinocytes act as a source of reactive oxygen species by transferring hydrogen peroxide to melanocytes. J Invest Dermatol 2005; 124: 793-797.

. Oršolić N, Skurić J, Dikić D, Stanić G. Inhibitory effect of a propolis on di-n-propyl disulfide or n-hexyl salycilate-induced skin irritation, oxidative stress and inflammatory responses in mice. Fitoterapia 2014; 93: 18-30.

. Skurić J, Oršolić N, Kolarić D, Đikić D, Benković V, Horvat-Knežević A, Lisičić D, et al. Effectivity of flavonoids on animal model psoriasis – thermographic evaluation. Period biol 2011; 113: 457-463.

. Zhou Q, Mrowietz U, Rostami-Yazdi M. Oxidative stress in the pathogenesis of psoriasis. Free Radic Biol Med 2009; 47: 891–905

. Middleton E JR, kandaswami C, theoharides TC. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease and cancer. Pharmacol Rev 2000; 52(4): 673-751.

. Oršolić N, Bašić I. Polyphenols from propolis and plants in control of allergy and inflammation. In: Oršolić N and Bašić I, editors. Scientific evidence of the use of propolis in ethnomedicine. Ethnopharmacology - Review Book, Transworld Research Network, India 2008. P. 311-336.

. Oršolić N., Bašić I. Propolis and plant flavonoids in human allergies and inflammations. In: Oršolić N and Bašić I, editors. Scientific evidence of the use of propolis in ethnomedicine. Ethnopharmacology- Review Book, Transworld Research Network, India 2008. p. 337-376.

. Oršolić N, Benković V, Horvat-Knežević A, Kopjar N, Kosalec I, Bakmaz M, Mihaljević Ž, Bendelja K, Bašić I. Assessment by survival analysis of the radioprotective properties of propolis and its polyphenolic compounds. Biol Pharm Bull 2007; 30(5): 946-51.

. Benković V, Oršolić N, Horvat-Knežević A, Ramić S, Dikić D, Basić I, Kopjar N. Evaluation of the radioprotective effects of propolis and flavonoids in gamma-irradiated mice: the alkaline comet assay study. Biol Pharm Bull 2008; 31: 167-172.

. Oršolić N, Benković V, Lisičić D, Dikić D, Erhardt J, Horvat-Knežević A. Protective effects of propolis and related polyphenolic/flavonoid compounds against toxicity induced by irinotecan. Med Oncol 2010; 27: 1346-1358.

. Oršolić N, Bašić I. Cancer chemoprevention by propolis and its polyphenolic compounds in experimental animals. In: Singh VK, Govil JN,.Arunahalam C. editors. Recent Progress in Medicinal Plants. Studium Press. Houston 2007. p. 55-113.

. García-Pérez ME, royer M, Duque-Fernandez A, Diouf PN, Stevanovic T, Pouliot R. Antioxidant, toxicological and antiproliferative properties of Canadian polyphenolic extracts on normal and psoriatic keratinocytes. J Ethnopharmacol 2010; 132(1): 251-8.

. Tornier C, Amsellem C, Fraissinette Ade B, Alépée N. Assessment of the optimized SkinEthic Reconstructed Human Epidermis (RHE) 42 bis skin irritation protocol over 39 test substances. Toxicol In Vitro 2010; 24(1):245-56.

. Noh SU, Cho EA, Kim HO, Park YM. Epigallocatechin-3-gallate improves Dermatophagoides pteronissinus extract-induced atopic dermatitis-like skin lesions in NC/Nga mice by supressing macrophage migration inhibitory factor. Int Immunopharmacol 2008; 8: 1172-1182.

. Oršolić N, Kunštić M, Kukolj M, Gračan R, Nemrava J. Oxidative stress, polarization of macrophages and tumour angiogenesis: Efficacy of caffeic acid. Chem Biol Interact 2016; 256:111-24

. Yildirim M, Inaloz HS, Baysal V, Delibas N. The role of oxidants and antioxidants in psoriasis. J Eur Acad Dermatol Venereol 2003; 17(1): 34-6.

. Lin X, Huang T. Oxidative stress in psoriasis and potential therapeutic use of antioxidants. Free Radic Res. 2016; 50(6): 585-95.

. Varga G, Ludwig S, Wixler V.Leite Dantas R, Masemann D, Schied T, Bergmeier V, Vogl T, Loser K. Brachvogel Macrophage-mediated psoriasis can be suppressed by regulatory T lymphocytes B. J Pathol 2016; 240(3): 366-377.

. Young, CN, Koepke, JI, Terlecky LJ, Borkin MS, Savoy LB, Terlecky SR. Reactive oxygen species in tumor necrosis fractor alpha activated primary human keratinocytes: implications for psoriasis and inflammatory skin disease. J Invest Dermatol 2008; 128: 2606–2614.

. Rocha-Pereira P, Santos-Silva A, Rebelo I, Figueiredo A, Quintanilha A, Teixeira F. The inflammatory response in mild and in severe psoriasis. Brit J Derm 2004; 150: 917–928.

. Kadam DP, Suryakar AN, Ankush RD, Kadam CY, Deshpande KH. Role of oxidative stress in various stages of psoriasis. Indian J Clin Biochem 2010; 25(4):388-92.

. Oršolić N, Saranović A, Bašić I. Direct and indirect mechanism(s) of antitumour activity of propolis and its polyphenolic compounds. Planta Med 2006; 72(1): 20-27.

. Oršolić N. A review of propolis antitumor action in vivo and in vitro. JAAS 2010; 2(1): 1-20.

. Gudjonsson JE, Johnston A, Dyson M, Valdimarsson H, Elder JT. Mouse Models of Psoriasis. J Invest Dermatol 2007; 127: 1292-1308.

. Boehncke WH, Schön MP. Animal models of psoriasis. Clin Dermatol 2007; 25: 596–605.

. Khavari PA. Modelling cancer in human skin tissue. Nat Rev Cancer 2006; 6: 270–280.

. Godfrey DI, Hammond KJ, Poulton LD, Smyth MJ, Baxter AG. NKT cells: facts, functions and fallacies. Immunol Today 2000; 21: 573–583.

. Skurić J, Oršolić N, Kolarić D, Đikić D, Benković V, Lisičić D, Horvat Knežević A., Maldini B. Thermography in Assessing the Inflammatory Skin Changes and Effectivity of Flavonoids on Animal Model Psoriasis. In: Jelena Božek, Mislav Grgić, editors. ELMAR-2011. Proceedings ELMAR-2011, Zadar; International Symposium Electronics in Marine -ELMAR, 14-16 Sept. 2011. p. 313-316.




How to Cite

Nada Orsolic, Vedran Balta, Dyana Odeh, Maja Mataković, Jadranka Skurić. Oxidative stress and inflammation caused by n-Hexyl salicylate in mouse skin: the effectiveness of flavonoids. ijp [Internet]. 2017 Jun. 30 [cited 2023 Nov. 30];9(2):279-88. Available from: https://ijp.arjournals.org/index.php/ijp/article/view/538



Original Research Articles

Most read articles by the same author(s)