Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
권호 표지
DOI QR코드

DOI QR Code

Combination of red ginseng and velvet antler extracts prevents skin damage by enhancing the antioxidant defense system and inhibiting MAPK/AP-1/NF-κB and caspase signaling pathways in UVB-irradiated HaCaT keratinocytes and SKH-1 hairless mice

  • Van-Long Truong (Food and Bio-industry Research Institute, School of Food Science & Biotechnology, College of Agriculture and Life Sciences, Kyungpook National University) ;
  • Yeon-Ji Bae (Food and Bio-industry Research Institute, School of Food Science & Biotechnology, College of Agriculture and Life Sciences, Kyungpook National University) ;
  • Ji-Hong Bang (Food and Bio-industry Research Institute, School of Food Science & Biotechnology, College of Agriculture and Life Sciences, Kyungpook National University) ;
  • Woo-Sik Jeong (Food and Bio-industry Research Institute, School of Food Science & Biotechnology, College of Agriculture and Life Sciences, Kyungpook National University)
  • Received : 2023.08.22
  • Accepted : 2024.01.11
  • Published : 2024.05.01
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Studies have reported that the combination of two or more therapeutic compounds at certain ratios has more noticeable pharmaceutical properties than single compounds and requires reduced dosage of each agent. Red ginseng and velvet antler have been extensively used in boosting immunity and physical strength and preventing diseases. Thus, this study was conducted to elucidate the skin-protective potentials of red ginseng extract (RGE) and velvet antler extract (VAE) alone or in combination on ultraviolet (UVB)-irradiated human keratinocytes and SKH-1 hairless mice. Methods: HaCaT cells were preincubated with RGE/VAE alone or in combination for 2 h before UVB (30 mJ/cm2) irradiation. SKH-1 mice were orally given RGE/VAE alone or in combination for 15 days before exposure to single dose of UVB (600 mJ/cm2). Treated cells and treated skin tissues were collected and subjected to subsequent experiments. Results: RGE/VAE pretreatment alone or in combination significantly prevented UVB-induced cell death, apoptosis, reactive oxygen species production, and DNA damage in keratinocytes and SKH-1 mouse skins by downregulating mitogen-activated protein kinases/activator protein 1/nuclear factor kappa B and caspase signaling pathways. These extracts also strengthened the antioxidant defense systems and skin barriers in UVB-irradiated HaCaT cells and SKH-1 mouse skins. Furthermore, RGE/VAE co-administration appeared to be more effective in preventing UVB-caused skin injury than these extracts used alone. Conclusion: Overall, these findings suggest that the consumption of RGE/VAE, especially in combination, offers a protective ability against UVB-caused skin injury by preventing inflammation and apoptosis and enhancing antioxidant capacity.

Keywords

Acknowledgement

This research was supported by the 2022 research grant from the Korean Society of Ginseng.

References

  1. Park J, Woo YK, Cho HJ. Regulation of anti-oxidative, anti-inflammatory, and antiapoptotic activity of advanced cooling composition (ACC) in UVB-irradiated human HaCaT keratinocytes. Int J Mol Sci 2020;21:6527.
  2. Afaq F, Syed DN, Malik A, Hadi N, Sarfaraz S, Kweon MH, et al. Delphinidin, an Anthocyanidin in pigmented fruits and vegetables, protects human HaCaT keratinocytes and mouse skin against UVB-mediated oxidative stress and apoptosis. J Invest Dermatol 2007;127:222-32. https://doi.org/10.1038/sj.jid.5700510
  3. Patel S, Rauf A. Adaptogenic herb ginseng (Panax) as medical food: status quo and future prospects. Biomed Pharmacother 2017;85:120-7. https://doi.org/10.1016/j.biopha.2016.11.112
  4. Lee SM, Bae BS, Park HW, Ahn NG, Cho BG, Cho YL, et al. Characterization of Korean red ginseng (Panax ginseng Meyer): History, preparation method, and chemical composition. J Ginseng Res 2015;39:384-91. https://doi.org/10.1016/j.jgr.2015.04.009
  5. Lee YM, Yoon H, Park HM, Song BC, Yeum KJ. Implications of red Panax ginseng in oxidative stress associated chronic diseases. J Ginseng Res 2017;41:113-9. https://doi.org/10.1016/j.jgr.2016.03.003
  6. So SH, Lee JW, Kim YS, Hyun SH, Han CK. Red ginseng monograph. J Ginseng Res 2018;42:549-61. https://doi.org/10.1016/j.jgr.2018.05.002
  7. Park SY, Shin YK, Kim HT, Kim YM, Lee DG, Hwang E, et al. A single-center, randomized, double-blind, placebo-controlled study on the efficacy and safety of "enzyme-treated red ginseng powder complex (BG11001)" for antiwrinkle and proelasticity in individuals with healthy skin. J Ginseng Res 2016;40:260-8. https://doi.org/10.1016/j.jgr.2015.08.006
  8. Park MY, Han SJ, Moon D, Kwon S, Lee JW, Kim KS. Effects of red ginseng on the elastic properties of human skin. J Ginseng Res 2020;44:738-46. https://doi.org/10.1016/j.jgr.2019.08.004
  9. Saba E, Kim SH, Lee YY, Park CK, Oh JW, Kim TH, et al. Korean Red Ginseng extract ameliorates melanogenesis in humans and induces antiphotoaging effects in ultraviolet B-irradiated hairless mice. J Ginseng Res 2020;44:496-505. https://doi.org/10.1016/j.jgr.2019.05.003
  10. Kim YH, Park HR, Cha SY, Lee SH, Jo JW, Go JN, et al. Effect of red ginseng NaturalGEL on skin aging. J Ginseng Res 2020;44:115-22. https://doi.org/10.1016/j.jgr.2018.09.006
  11. Ahn H, Han BC, Hong EJ, An BS, Lee E, Lee SH, et al. Korean Red Ginseng attenuates ultraviolet-mediated inflammasome activation in keratinocytes. J Ginseng Res 2021;45:456-63. https://doi.org/10.1016/j.jgr.2021.02.002
  12. Lee HJ, Kim JS, Song MS, Seo HS, Moon C, Kim JC, et al. Photoprotective effect of red ginseng against ultraviolet radiation-induced chronic skin damage in the hairless mouse. Phytother Res 2009;23:399-403. https://doi.org/10.1002/ptr.2640
  13. Sui Z, Zhang L, Huo Y, Zhang Y. Bioactive components of velvet antlers and their pharmacological properties. J Pharm Biomed Anal 2014;87:229-40. https://doi.org/10.1016/j.jpba.2013.07.044
  14. Kawtikwar PS, Bhagwat DA, Sakarkar DM. Deer antlers- Traditional use and future perspectives. Indian J Tradit Knowl 2010;9:245-51.
  15. Wu F, Li H, Jin L, Li X, Ma Y, You J, et al. Deer antler base as a traditional Chinese medicine: a review of its traditional uses, chemistry and pharmacology. J Ethnopharmacol 2013;145:403-15. https://doi.org/10.1016/j.jep.2012.12.008
  16. Roh SS, Lee MH, Hwang YL, Song HH, Jin MH, Park SG, et al. Stimulation of the extracellular matrix production in dermal fibroblasts by velvet antler extract. Ann Dermatol 2010;22:173-9.
  17. Tansathien K, Suriyaaumporn P, Charoenputtakhun P, Ngawhirunpat T, Opanasopit P, Rangsimawong W. Development of sponge microspicule cream as a transdermal delivery system for protein and growth factors from deer antler velvet extract. Biol Pharm Bull 2019;42:1207-15. https://doi.org/10.1248/bpb.b19-00158
  18. Tansathien K, Chareanputtakhun P, Ngawhirunpat T, Opanasopit P, Rangsimawong W. Hair growth promoting effect of bioactive extract from deer antler velvet-loaded niosomes and microspicules serum. Int J Pharm 2021;597:120352.
  19. Ting-Chao C. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev 2006;58:621-81. https://doi.org/10.1124/pr.58.3.10
  20. Saba E, Lee YY, Kim M, Hyun SH, Park CK, Son E, et al. A novel herbal formulation consisting of red ginseng extract and Epimedium koreanum Nakai-attenuated dextran sulfate sodium-induced colitis in mice. J Ginseng Res 2020;44:833-42. https://doi.org/10.1016/j.jgr.2020.02.003
  21. So SH, Lee SK, Hwang EI, Koo BS, Han GH, Chung JH, et al. Mechanisms of Korean red ginseng and herb extracts (KTNG0345) for anti-wrinkle activity. J Ginseng Res 2008;32:39-47. https://doi.org/10.5142/JGR.2008.32.1.039
  22. Suh JH, Seo HW, Han BC, Kyung JS, So SH. 13-Week repeated oral dose toxicity study on mixture of Korean red ginseng and deer antler extract in Sprague-Dawley rats. Toxicol Res 2020;36:1-12. https://doi.org/10.1007/s43188-019-00005-5
  23. Kim YA, Kim SW, Lee MH, Lee HK, Hwang IH. Comparisons of chemical composition, flavor and bioactive substances between Korean and imported velvet antler extracts. Food Sci Anim Resour 2021;41:386-401. https://doi.org/10.5851/kosfa.2021.e4
  24. Choi JY, Woo TS, Yoon SY, Ike Campomayor Dela P, Choi YJ, Ahn HS, et al. Red ginseng supplementation more effectively alleviates psychological than physical fatigue. J Ginseng Res 2011;35:331-8. https://doi.org/10.5142/jgr.2011.35.3.331
  25. Choi YJ, Fan M, Yu Y, Wang X, Tang Y, Kim EK. Sika deer (Cervus nippon) velvet antler ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis-like clinical signs in a rodent model. Anim Prod Sci 2020;60:1357-63. https://doi.org/10.1071/AN19500
  26. Kim OK, Kim D, Lee M, Park SH, Yamada W, Eun S, et al. Standardized edible Bird's nest extract prevents UVB irradiation-mediated oxidative stress and photoaging in the skin. Antioxidants 2021;10:1452.
  27. Hou GR, Zeng K, Lan HM, Wang Q. Juglanin ameliorates UVB-induced skin carcinogenesis via anti-inflammatory and proapoptotic effects in vivo and in vitro. Int J Mol Med 2018;42:41-52.
  28. Caricchio R, McPhie L, Cohen PL. Ultraviolet B radiation-induced cell death: critical role of ultraviolet dose in inflammation and Lupus Autoantigen Redistribution. J Immun 2003;171:5778-86. https://doi.org/10.4049/jimmunol.171.11.5778
  29. Lee CH, Wu SB, Hong CH, Yu HS, Wei YH. Molecular mechanisms of UV-induced apoptosis and its effects on skin residential cells: the implication in UV-based phototherapy. Int J Mol Sci 2013;14:6414-35. https://doi.org/10.3390/ijms14036414
  30. Kulms D, Schwarz T. Independent contribution of three different pathways to ultraviolet-B-induced apoptosis. Biochem Pharmacol 2002;64:837-41. https://doi.org/10.1016/S0006-2952(02)01146-2
  31. Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2002;2:647-56. https://doi.org/10.1038/nrc883
  32. Newmeyer DD, Ferguson-Miller S. Mitochondria: releasing power for life and unleashing the machineries of death. Cell 2003;112:481-90. https://doi.org/10.1016/S0092-8674(03)00116-8
  33. Chang Howard Y, Yang X. Proteases for cell suicide: functions and regulation of caspases. Microbiol Mol Biol Rev 2000;64:821-46. https://doi.org/10.1128/MMBR.64.4.821-846.2000
  34. Porter AG, Janicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ 1999;6:99-104. https://doi.org/10.1038/sj.cdd.4400476
  35. Truong VL, Keum YS, Jeong WS. Red ginseng oil promotes hair growth and protects skin against UVC radiation. J Ginseng Res 2021;45:498-509. https://doi.org/10.1016/j.jgr.2020.12.008
  36. Miodovnik M, Koren R, Ziv E, Ravid A. The inflammatory response of keratinocytes and its modulation by vitamin D: the role of MAPK signaling pathways. J Cell Physiol 2012;227:2175-83.
  37. Shibata A, Nakagawa K, Kawakami Y, Tsuzuki T, Miyazawa T. Suppression of γ-Tocotrienol on UVB induced inflammation in HaCaT keratinocytes and HR-1 hairless mice via inflammatory mediators multiple signaling. J Agric Food Chem 2010;58:7013-20. https://doi.org/10.1021/jf100691g
  38. Tripp CS, Blomme EAG, Chinn KS, Hardy MM, LaCelle P, Pentland AP. Epidermal COX-2 induction following ultraviolet irradiation: suggested mechanism for the role of COX-2 inhibition in photoprotection. J Invest Dermatol 2003;121:853-61. https://doi.org/10.1046/j.1523-1747.2003.12495.x
  39. Lee JL, Mukhtar H, Bickers DR, Kopelovich L, Athar M. Cyclooxygenases in the skin: pharmacological and toxicological implications. Toxicol Appl Pharmacol 2003;192:294-306. https://doi.org/10.1016/S0041-008X(03)00301-6
  40. Cooper S, Ranger-Moore J, Bowden TG. Differential inhibition of UVB-induced AP1 and NF-κB transactivation by components of the jun bZIP domain. Mol Carcinog 2005;43:108-16.
  41. Cooper SJ, Bowden GT. Ultraviolet B regulation of transcription factor families: roles of nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) in UVB-induced skin carcinogenesis. Curr Cancer Drug Targets 2007;7:325-34. https://doi.org/10.2174/156800907780809714
  42. Bode AM, Dong Z. Mitogen-activated protein kinase activation in UV-induced signal transduction. Sci STKE 2003;2003:re2.
  43. Shin SW, Jung E, Kim S, Kim JH, Kim EG, Lee J, et al. Antagonizing effects and mechanisms of afzelin against UVB-induced cell damage. PLoS One 2013;8:e61971.
  44. Pratheeshkumar P, Son YO, Wang X, Divya SP, Joseph B, Hitron JA, et al. Cyanidin-3-glucoside inhibits UVB-induced oxidative damage and inflammation by regulating MAP kinase and NF-κB signaling pathways in SKH-1 hairless mice skin. Toxicol Appl Pharmacol 2014;280:127-37. https://doi.org/10.1016/j.taap.2014.06.028
  45. Halliday GM. Inflammation, gene mutation and photoimmunosuppression in response to UVR-induced oxidative damage contributes to photocarcinogenesis. Mutat Res 2005;571:107-20. https://doi.org/10.1016/j.mrfmmm.2004.09.013
  46. Li XQ, Cai LM, Liu J, Ma YL, Kong YH, Li H, et al. Liquiritin suppresses UVBinduced skin injury through prevention of inflammation, oxidative stress and apoptosis through the TLR4/MyD88/NF-κB and MAPK/caspase signaling pathways. Int J Mol Med 2018;42:1445-59.
  47. Chaiprasongsuk A, Janjetovic Z, Kim TK, Jarrett SG, D'Orazio JA, Holick MF, et al. Protective effects of novel derivatives of vitamin D3 and lumisterol against UVB-induced damage in human keratinocytes involve activation of Nrf2 and p53 defense mechanisms. Redox Biol 2019;24:101206.
  48. Tao S, Justiniano R, Zhang DD, Wondrak GT. The Nrf2-inducers tanshinone I and dihydrotanshinone protect human skin cells and reconstructed human skin against solar simulated UV. Redox Biol 2013;1:532-41. https://doi.org/10.1016/j.redox.2013.10.004
  49. Saw CL, Huang MT, Liu Y, Khor TO, Conney AH, Kong AN. Impact of Nrf2 on UVB-induced skin inflammation/photoprotection and photoprotective effect of sulforaphane. Mol Carcinog 2011;50:479-86. https://doi.org/10.1002/mc.20725
  50. Hirota A, Kawachi Y, Yamamoto M, Koga T, Hamada K, Otsuka F. Acceleration of UVB-induced photoageing in nrf2 gene-deficient mice. Exp Dermatol 2011;20:664-8. https://doi.org/10.1111/j.1600-0625.2011.01292.x
  51. Han EJ, Kim SY, Han HJ, Kim HS, Kim KN, Fernando IPS, et al. UVB protective effects of Sargassum horneri through the regulation of Nrf2 mediated antioxidant mechanism. Sci Rep 2021;11:9963.
  52. Li K, Zhang M, Chen H, Peng J, Jiang F, Shi X, et al. Anthocyanins from black peanut skin protect against UV-B induced keratinocyte cell and skin oxidative damage through activating Nrf 2 signaling. Food Funct 2019;10:6815-28. https://doi.org/10.1039/C9FO00706G
  53. Gaschler MM, Stockwell BR. Lipid peroxidation in cell death. Biochem Biophys Res Commun 2017;482:419-25. https://doi.org/10.1016/j.bbrc.2016.10.086
  54. Yadav DK, Kumar S, Choi EH, Chaudhary S, Kim MH. Molecular dynamic simulations of oxidized skin lipid bilayer and permeability of reactive oxygen species. Sci Rep 2019;9:4496.
  55. Li Z, Jiang R, Wang M, Zhai L, Liu J, Xu X, et al. Ginsenosides repair UVB-induced skin barrier damage in BALB/c hairless mice and HaCaT keratinocytes. J Ginseng Res 2022;46:115-25. https://doi.org/10.1016/j.jgr.2021.05.001
  56. Li Z, Jiang R, Jing C, Liu J, Xu X, Sun L, et al. Protective effect of oligosaccharides isolated from Panax ginseng C. A. Meyer against UVB-induced skin barrier damage in BALB/c hairless mice and human keratinocytes. J Ethnopharmacol 2022;283:114677.