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Antioxidant, anti-inflammatory, and anti-pruritic effects of grape branch extract

포도가지 추출물의 산화방지, 항염증 및 항가려움 효과

  • 조병옥 ((주)아토큐앤에이 기업부설연구소) ;
  • 윤홍화 ((주)아토큐앤에이 기업부설연구소) ;
  • 체 데니스 창 (전주대학교 보건관리학과) ;
  • 김상준 ((재)전주농생명소재연구원) ;
  • 유철 ((주)향미원) ;
  • 장선일 ((주)아토큐앤에이 기업부설연구소)
  • Received : 2016.06.07
  • Accepted : 2016.07.07
  • Published : 2016.12.31

Abstract

This study was designed to investigate the antioxidant activities of the ethanol extracts (GBE) of grape branches (Campbell Early). The total polyphenol and flavonoid content of GBE was $201.42{\pm}4.16$ and $11.85{\pm}0.44mg\;GAE/g$, respectively. The antioxidant activity of GBE was measured using the ABTS and DPPH assays, and the $IC_{50}$ values were $45.60{\pm}0.09$ and $299.13{\pm}0.22$, respectively. GBE inhibited the production of pro-inflammatory mediators (NO, iNOS, $PGE_2$, COX-2, $IL-1{\beta}$, and IL-6) in lipopolysaccharide-stimulated RAW 264.7 macrophages in a dose-dependent manner. Moreover, GBE treatment significantly suppressed the production of $TNF-{\alpha}$ and IL-6 cytokines in phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated HMC-1 human mast cells. Furthermore, the administration of GBE markedly inhibited the scratching behavior induced by the compound 48/80 in ICR mice. These results suggested that GBE has potential as a therapeutic agent against inflammation and itch-related skin diseases.

본 연구에서는 우리나라에서 가장 많이 재배되고 있는 캠벨어얼리 포도 품종에서 포도가지를 대상으로 산화방지, 항염증 및 항가려움증 효과를 검증하고 활성물질을 나타내는 지표물질을 추적 조사하였다. 그 결과 포도가지 추출물의 총 폴리페놀과 총 플라보노이드 함량은 각각 $201.42{\pm}4.16$$11.85{\pm}0.44mg\;GAE/g$으로 조사되었다. 또한 캠벨어얼리 포도가지 추출물의 ABTS와 DPPH 라디칼 소거 활성은 각각 $45.60{\pm}0.09$ ($IC_{50}$)과 $299.13{\pm}0.22$ ($IC_{50}$)으로 나타나 산화방지 활성이 우수하였다. 게다가 캠벨어얼리 포도가지 추출물은 지방질다당류로 활성화된 RAW 264.7 세포에서 전염증성 매개물인 산화질소와 프로스타글란딘 $E_2$를 iNOS와 COX-2 분자 발현 억제를 통하여 억제하였고, 전염증성 사이토카인인 인터류킨-1베타와 인터류킨-6를 농도 의존적으로 억제하는 효능이 있었다. 더욱이 phorbol 12-myristate 13-acetate (PMA)와 calcium ionophore A23187로 활성화된 인간 유래 비만세포인 HMC-1 세포에서 종양괴사인자-알파와 인터류킨-6를 농도 의존적으로 억제하는 효능이 있었다. 마지막으로 Compound 48/80으로 유도되는 마우스 가려움증을 캠벨어얼리 포도가지 추출물은 효과적으로 억제하였다. 이러한 캠벨어얼리 추출물에서 활성을 나타내는 물질을 추적한 결과 레스베라트롤의 함량이 높게 검출되었다. 그러므로 본 연구의 결과를 종합해 볼 때 캠벨어얼리 포도가지 추출물은 아토피 질환에서 나타나는 염증과 가려움증을 효과적으로 제어할 수 있는 효과적인 소재임을 제시하였다.

Keywords

References

  1. Finlay AY. Quality of life in atopic dermatitis. J. Am. Acad. Dermatol. 45: S64-S66 (2001) https://doi.org/10.1067/mjd.2001.117010
  2. Shishido T, Nozaki N, Takahashi H, Arimoto T, Niizeki T, Koyama Y, Abe J, Takeishi Y, Kubota I. Central role of endogenous Toll-like receptor-2 activation in regulating inflammation, reactive oxygen species production, and subsequent neointimal formation after vascular injury. Biochem. Biophys. Res. Commun. 345: 1446-1453 (2006) https://doi.org/10.1016/j.bbrc.2006.05.056
  3. Okayama Y. Oxidative stress in allergic and inflammatory skin diseases. Curr. Drug Targets Inflamm. Allergy 4: 517-519 (2005) https://doi.org/10.2174/1568010054526386
  4. Bickers DR, Athar M. Oxidative stress in the pathogenesis of skin disease. J. Invest. Dermatol. 126: 2565-2575 (2006) https://doi.org/10.1038/sj.jid.5700340
  5. Wink DA, Hanbauer I, Grisham MB, Laval F, Nims RW, Laval J, Cook J, Pacelli R, Liebmann J, Krishna M, Ford PC, Mitchell JB. Chemical biology of nitric oxide: Regulation and protective and toxic mechanisms. Curr. Top. Cell Regul. 34: 159-187 (1996) https://doi.org/10.1016/S0070-2137(96)80006-9
  6. Bouayed J, Bohn T. Exogenous antioxidants-double-edged swords in cellular redox state: Health beneficial effects at physiologic doses versus deleterious effects at high doses. Oxid. Med. Cell Longev. 3: 228-237 (2010) https://doi.org/10.4161/oxim.3.4.12858
  7. Iacopini P, Baldi M, Storchi P, Sebastiani L. Catechin, epicatechin, quercetin, rutin and resveratrol in red grape: Content, in vitro antioxidant activity and interactions. J. Food Compos. Anal. 21: 589-598 (2008) https://doi.org/10.1016/j.jfca.2008.03.011
  8. Baxter RA. Anti-aging properties of resveratrol: Review and report of a potent new antioxidant skin care formulation. J. Cosmet. Dermatol. 7: 2-7 (2008) https://doi.org/10.1111/j.1473-2165.2008.00354.x
  9. Bishayee A. Cancer prevention and treatment with resveratrol: From rodent studies to clinical trials. Cancer Prev. Res. 2: 409-418 (2009) https://doi.org/10.1158/1940-6207.CAPR-08-0160
  10. Lee SM, Yang H, Tartar DM, Gao B, Luo X, Ye SQ, Zaghouani H, Fang D. Prevention and treatment of diabetes with resveratrol in a non-obese mouse model of type 1 diabetes. Diabetologia 54: 1136-1146 (2011) https://doi.org/10.1007/s00125-011-2064-1
  11. Azorin-Ortuno M, Yanez-Gascon MJ, Pallares FJ, Rivera J, Gonzalez-Sarrias A, Larrosa M, Vallejo F, Garcia-Conesa MT, Tomas-Barberan F, Espin JC. A dietary resveratrol-rich grape extract prevents the developing of atherosclerotic lesions in the aorta of pigs fed an atherogenic diet. J. Agr. Food Chem. 60: 5609-5620 (2012) https://doi.org/10.1021/jf301154q
  12. Kang HJ, Kim HS, Jeon IH, Mok JY, Han KS, Jang SI. Effects of antioxidant and blood flow improvement of grape leaf extract and resveratrol from vitis romaneti. J. Korean Soc. Food Sci. Nutr. 42: 1736-1743 (2013) https://doi.org/10.3746/jkfn.2013.42.11.1736
  13. Chang EH, Jeong SM, Park KS, Lim BS. Contents of phenolic compounds and trans-resveratrol in different parts of Korean new grape cultivars. Korean J. Food Sci. Thechol. 45: 708-713 (2013) https://doi.org/10.9721/KJFST.2013.45.6.708
  14. Blainski A, Lopes GC, de Mello JC. Application and analysis of the folin ciocalteu method for the determination of the total phenolic content from Limonium Brasiliense L. Molecules 18: 6852-6865 (2013) https://doi.org/10.3390/molecules18066852
  15. Moreno DA, Carvajal M, Lopez-Berenguer C, Garcoa-Viguera C. Chemical and biological characterisation of nutraceutical compounds of broccoli. J. Pharm. Biomed. Anal. 41: 1508-1522 (2006) https://doi.org/10.1016/j.jpba.2006.04.003
  16. Blois MS. Antioxidant determination by the use of a stable free radical. Nature 181: 1199-1200 (1958) https://doi.org/10.1038/1811199a0
  17. Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic. Biol. Med. 26: 1231-1237 (1999) https://doi.org/10.1016/S0891-5849(98)00315-3
  18. Mihara K, Kuratani K, Matsui T, Nakamura M, Yokota K. Vital role of the itch-scratch response in development of spontaneous dermatitis in NC/Nga mice. Br. J. Dermatol. 151: 335-345 (2004) https://doi.org/10.1111/j.1365-2133.2004.06036.x
  19. Kim JH, Choi SK, Yu YS, Yoon KS, Seo JS. Physiologically active components and antioxidant capacity of grapevine leaves at growth stages. Korean J. Food Sci. Technol. 44: 772-778 (2012) https://doi.org/10.9721/KJFST.2012.44.6.772
  20. Coleman JW. Nitric oxide in immunity and inflammation. Int. Immunopharmacol. 1: 1397-1406 (2001) https://doi.org/10.1016/S1567-5769(01)00086-8
  21. Giroux M, Descoteaux A. Cyclooxygenase-2 expression in macrophages: Modulation by protein kinase C-alpha. J. Immunol. 165: 3985-3991 (2000) https://doi.org/10.4049/jimmunol.165.7.3985
  22. Marchi P, Paiotti AP, Artigiani Neto R, Oshima CT, Ribeiro DA. Concentrated grape juice (G8000TM) reduces immunoexpression of iNOS, TNF-alpha, COX-2 and DNA damage on 2,4,6-trinitrobenzene sulfonic acid-induced-colitis. Environ. Toxicol. Pharmacol. 37: 819-827 (2014) https://doi.org/10.1016/j.etap.2014.02.006
  23. Bak MJ, Truong VL, Kang HS, Jun M, Jeong WS. Anti-inflammatory effect of procyanidins from wild grape (Vitis amurensis) seeds in LPS-induced RAW 264.7 cells. Oxid. Med. Cell Longev. 2013: 409321 (2013)
  24. Filip GA, Postescu ID, Bolfa P, Catoi C, Muresan A, Clichici S. Inhibition of UVB-induced skin phototoxicity by a grape seed extract as modulator of nitrosative stress, ERK/NF-kB signaling pathway and apoptosis, in SKH-1 mice. Food Chem. Toxicol. 57: 296-306 (2013) https://doi.org/10.1016/j.fct.2013.03.031
  25. Yoon CS, Kim DC, Ko WM, Kim KS, Lee DS, Kim DS, Cho HK, Seo J, Kim SY, Oh H, Kim YC. Anti-neuroinflammatory effects of quercetin-3-O-glucuronide isolated from the leaf of Vitis labruscana on LPS-induced neuroinflammation in BV2 cells. Kor. J. Pharmacogn. 45: 17-22 (2014)
  26. Greenspan P, Bauer JD, Pollock SH, Gangemi JD, Mayer EP, Ghaffar A, Hargrove JL, Hartle DK. Antiinflammatory properties of the muscadine grape (Vitis rotundifolia). J Agr. Food Chem. 53: 8481-8484 (2005) https://doi.org/10.1021/jf058015+
  27. Kalinski P. Regulation of immune responses by prostaglandin $E_2$. J. Immunol. 188: 21-28 (2012) https://doi.org/10.4049/jimmunol.1101029
  28. Boguniewicz M, Leung DY. Atopic dermatitis: A disease of altered skin barrier and immune dysregulation. Immunol. Rev. 242: 233-246 (2011) https://doi.org/10.1111/j.1600-065X.2011.01027.x
  29. Numerof RP, Asadullah K. Cytokine and anti-cytokine therapies for psoriasis and atopic dermatitis. BioDrugs 20: 93-103 (2006) https://doi.org/10.2165/00063030-200620020-00004
  30. Heo KS, Fujiwara K, Abe J. Disturbed-flow-mediated vascular reactive oxygen species induce endothelial dysfunction. Circ. J. 75: 2722-2730 (2011) https://doi.org/10.1253/circj.CJ-11-1124
  31. Eichenfield LF, Ellis CN, Mancini AJ, Paller AS, Simpson EL. Atopic dermatitis: Epidemiology and pathogenesis update. Semin. Cutan. Med. Surg. 31: S3-S5 (2012) https://doi.org/10.1016/j.sder.2012.07.002
  32. Tominaga M, Takamori K. Itch and nerve fibers with special reference to atopic dermatitis: Therapeutic implications. J. Dermatol. 41: 205-212 (2014) https://doi.org/10.1111/1346-8138.12317