Journal of Ginseng Research

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

DOI QR Code

Skin wound healing effects of (+)-syringaresinol from ginseng berry

  • Jee-hyun Hwang (College of Pharmacy, Ewha Womans University) ;
  • Yeonsoo Kang (College of Pharmacy, Ewha Womans University) ;
  • Heui-Jin Park (College of Pharmacy, Ewha Womans University) ;
  • Seolyeong Kim (Biosolution Co) ;
  • Su-Hyun Lee (Biosolution Co) ;
  • Hangun Kim (College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University) ;
  • Sang-Jip Nam (Department of Chemistry and Nanoscience, Ewha Womans University) ;
  • Kyung-Min Lim (College of Pharmacy, Ewha Womans University)
  • Received : 2022.10.06
  • Accepted : 2023.04.09
  • Published : 2023.09.01
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Ginseng has been used as a traditional medicine and functional cosmetic ingredients for many years. Recent studies have focused on the potential biological effects of the ginseng berry and its ingredients. (+)-Syringaresinol (SYR) is enriched in ginseng berry and its beneficial effects on the skin have been recently reported. However, little is known about the its effects on the wound healing process of skin. Methods: Here, we evaluated the skin wound healing effect of (+)-SYR using the human fibroblast Hs68 cell and ex vivo pig and human skin tissue model. Scratch wound test and hydrogen peroxide (HPO) induce chemical wound model were employed. Results: (+)-SYR promoted the migration and proliferation of Hs68 cells without significant cytotoxicity at the tested concentrations. Especially, in ex vivo pig and human skin tissue, HPO-induced chemical wound was recovered almost completely by (+)-SYR. In line with the finding in Hs68, the protein expression levels of TGF-β and PCNA, a proliferation marker were increased, demonstrating the beneficial effects of (+)-SYR on skin wound repair. Conclusion: Collectively, we demonstrated that (+)-SYR from ginseng berry, can enhance the wound healing effect by accelerating cell proliferation and skin regeneration, suggesting the potential utility of (+)-SYR for skin wound repair.

Keywords

Acknowledgement

This work was supported by grants from National Research Foundation of Korea (Grant No. 2021R1A2C2013347 and MSIT 2018R1A5A2025286).

References

  1. Ansell DM, Holden KA, Hardman M. Animal models of wound repair: are they cutting it? Exp Dermatol 2012;21(8):581-5. https://doi.org/10.1111/j.1600-0625.2012.01540.x
  2. Attele AS, Wu JA, Yuan C-S. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol 1999;58(11):1685-93. https://doi.org/10.1016/S0006-2952(99)00212-9
  3. Bajpai VK, Alam MB, Quan KT, Ju M-K, Majumder R, Shukla S, Huh YS, Na M, Lee SH, Han Y-K. Attenuation of inflammatory responses by (+)-syringaresinol via MAP-Kinase-mediated suppression of NF-kB signaling in vitro and in vivo. Sci Rep 2018;8(1):1-10.
  4. Bankhead P, Loughrey MB, Fernandez JA, Dombrowski Y, McArt DG, Dunne PD, McQuaid S, Gray RT, Murray LJ, Coleman HG. QuPath: open source software for digital pathology image analysis. Sci Rep 2017;7(1):1-7. https://doi.org/10.1038/s41598-016-0028-x
  5. Barrientos S, Stojadinovic O, Golinko MS, Brem H, Mjwr Tomic-Canic, regeneration. Growth Factors and Cytokines in Wound Healing, 16; 2008. p. 585-601. 5. https://doi.org/10.1111/j.1524-475X.2008.00410.x
  6. Bennett S, Griffiths G, Schor A, Leese G, Schor S. Growth factors in the treatment of diabetic foot ulcers. Br J Surg 2003;90(2):133-46. https://doi.org/10.1002/bjs.4019
  7. Bielefeld KA, Amini-Nik S, Alman BA. Cutaneous wound healing: recruiting developmental pathways for regeneration. Cellular and Molecular Life Sciences 2013;70(12):205-81. https://doi.org/10.1007/s00018-012-1039-9
  8. Cai C, Guo Z, Yang Y, Geng Z, Tang L, Zhao M, Qiu Y, Chen Y, He P. Inhibition of hydrogen peroxide induced injuring on human skin fibroblast by Ulva prolifera polysaccharide. International Journal of Biological Macromolecules 2016;91:241-7. https://doi.org/10.1016/j.ijbiomac.2016.05.071
  9. Cheon S, Poon R, Yu C, Khoury M, Shenker R, Fish J, Alman BA. Prolonged β-catenin stabilization and tcf-dependent transcriptional activation in hyperplastic cutaneous wounds. Laboratory Investigation 2005;85(3):416-25. https://doi.org/10.1038/labinvest.3700237
  10. Cheon SS, Cheah AY, Turley S, Nadesan P, Poon R, Clevers H, Alman BA. β-Catenin stabilization dysregulates mesenchymal cell proliferation, motility, and invasiveness and causes aggressive fibromatosis and hyperplastic cutaneous wounds. Proceedings of the National Academy of Sciences 2002;99(10):6973-8. https://doi.org/10.1073/pnas.102657399
  11. Choi W, Kim HS, Park SH, Kim D, Hong YD, Kim JH, Cho JY. Syringaresinol derived from Panax ginseng berry attenuates oxidative stress-induced skin aging via autophagy. Journal of Ginseng Research 2022;46(4):536-42. https://doi.org/10.1016/j.jgr.2021.08.003
  12. Christensen LP. Ginsenosides: chemistry, biosynthesis, analysis, and potential health effects. Advances in Food and Nutrition Research 2008;55:1-99. https://doi.org/10.1016/S1043-4526(08)00401-4
  13. Clark R, Nielsen LD, Welch MP, McPherson JM. Collagen matrices attenuate the collagen-synthetic response of cultured fibroblasts to TGF-beta. Journal of Cell Science 1995;108(3):1251-61.
  14. Demidova-Rice TN, Durham JT, Herman IM. Wound healing angiogenesis: innovations and challenges in acute and chronic wound healing. Advances in Wound Care 2012;1(1):17-22. https://doi.org/10.1089/wound.2011.0308
  15. Desmouliere A, Geinoz A, Gabbiani F, Gabbiani G. Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. The Journal of Cell Biology 1993;122(1):103-11. https://doi.org/10.1083/jcb.122.1.103
  16. Dey L, Xie J, Wang A, Wu J, Maleckar S, Yuan C-S. Anti-hyperglycemic effects of ginseng: comparison between root and berry. Phytomedicine 2003;10(6-7):600-5. https://doi.org/10.1078/094471103322331908
  17. Diekmann J, Alili L, Scholz O, Giesen M, Holtkotter O, Brenneisen P. A three-dimensional skin equivalent reflecting some aspects of in vivo aged skin. Experimental Dermatology 2016;25(1):56-61. https://doi.org/10.1111/exd.12866
  18. Dijkgraaf FE, Matos TR, Hoogenboezem M, Toebes M, Vredevoogd DW, Mertz M, van den Broek B, Song J-Y, Teunissen M, Luiten RM. Tissue patrol by resident memory CD8+ T cells in human skin. Nature Immunology 2019;20(6):756-64. https://doi.org/10.1038/s41590-019-0404-3
  19. Driskell RR, Lichtenberger BM, Hoste E, Kretzschmar K, Simons BD, Charalambous M, Ferron SR, Herault Y, Pavlovic G, Ferguson-Smith ACJN. Distinct Fibroblast Lineages Determine Dermal Architecture in Skin Development and Repair, 504; 2013. p. 277-81. 7479. https://doi.org/10.1038/nature12783
  20. Duda DG, Fukumura D, Jain RK. Role of eNOS in neovascularization: NO for endothelial progenitor cells. Trends in Molecular Medicine 2004;10(4):143-5. https://doi.org/10.1016/j.molmed.2004.02.001
  21. Duscher D, Maan ZN, Wong VW, Rennert RC, Januszyk M, Rodrigues M, Hu M, Whitmore AJ, Whittam AJ, Mtjjob Longaker. Mechanotransduction and Fibrosis, 47; 2014. p. 1997-2005. 9. https://doi.org/10.1016/j.jbiomech.2014.03.031
  22. Finnson KW, McLean S, Di Guglielmo GM, Philip A. Dynamics of transforming growth factor beta signaling in wound healing and scarring. Advances in Wound Care 2013;2(5):195-214. https://doi.org/10.1089/wound.2013.0429
  23. Gurtner GC, Werner S, Barrandon Y, Longaker M. Wound repair and regeneration. Nature 2008;453(7193):314-21. https://doi.org/10.1038/nature07039
  24. Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature 2008;453(7193):314-21. https://doi.org/10.1038/nature07039
  25. Hahn HJ, Kim KB, An IS, Ahn KJ, Han HJ. Protective effects of rosmarinic acid against hydrogen peroxide-induced cellular senescence and the inflammatory response in normal human dermal fibroblasts. Molecular Medicine Reports 2017;16(6):9763-9. https://doi.org/10.3892/mmr.2017.7804
  26. Hantash BM, Zhao L, Knowles JA, Lorenz HPJFB. Adult and Fetal Wound Healing, 13; 2008. p. 51-61. 1. https://doi.org/10.2741/2559
  27. He X, de Oliveira VL, Keijsers R, Joosten I, Koenen HJ. Lymphocyte isolation from human skin for phenotypic analysis and ex vivo cell culture. JoVE 2016;110:e52564. https://doi.org/10.3791/52564-v
  28. Hinz B, Gabbiani G. Cell-matrix and cell-cell contacts of myofibroblasts: role in connective tissue remodeling. Thrombosis and Haemostasis 2003;90(12):993-1002. https://doi.org/10.1160/TH03-05-0328
  29. Karppinen S-M, Heljasvaara R, Gullberg D, Tasanen K, Pihlajaniemi T. Toward understanding scarless skin wound healing and pathological scarring. F1000Research 2019;8.
  30. Kim C-K, Cho DH, Lee K-S, Lee D-K, Park C-W, Kim WG, Lee SJ, Ha K-S, Goo Taeg O, Kwon Y-G. Ginseng berry extract prevents atherogenesis via anti-inflammatory action by upregulating phase II gene expression. Evidence-based Complementary and Alternative Medicine 2012 2012.
  31. Kim H-G, Cho J-H, Yoo S-R, Lee J-S, Han J-M, Lee N-H, Ahn Y-C, Son C-G. Antifatigue effects of Panax ginseng CA Meyer: a randomised, double-blind, placebo-controlled trial. PloS One 2013;8(4):e61271.
  32. Kim J, Cho SY, Kim SH, Kim S, Park C-W, Cho D, Seo DB, Shin SS. Ginseng berry and its biological effects as a natural phytochemical. Natural Products Chemistry & Research 2016.
  33. Kim J, Toda T, Watanabe K, Shibuya S, Ozawa Y, Izuo N, Cho S, Seo DB, Yokote K, Shimizu T. Syringaresinol reverses age-related skin atrophy by suppressing FoxO3a-mediated matrix Metalloproteinase-2 activation in copper/zinc superoxide Dismutase-Deficient mice. Journal of Investigative Dermatology 2019;139(3):648-55. https://doi.org/10.1016/j.jid.2018.10.012
  34. Kim JH, Yi Y-S, Kim M-Y, Cho JY. Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases. Journal of Ginseng Research 2017;41(4):435-43. https://doi.org/10.1016/j.jgr.2016.08.004
  35. Kurayoshi M, Oue N, Yamamoto H, Kishida M, Inoue A, Asahara T, Yasui W, Kikuchi AJCr. Expression of Wnt-5a Is Correlated with Aggressiveness of Gastric Cancer by Stimulating Cell Migration and Invasion, 66; 2006. p. 10439-48. 21. https://doi.org/10.1158/0008-5472.CAN-06-2359
  36. Lu J-M, Yao Q, Chen C. Ginseng compounds: an update on their molecular mechanisms and medical applications. Current Vascular Pharmacology 2009;7(3):293-302. https://doi.org/10.2174/157016109788340767
  37. Oh JH, Joo YH, Karadeniz F, Ko J, Kong C-S. Syringaresinol inhibits UVA-induced MMP-1 expression by suppression of MAPK/AP-1 signaling in HaCaT keratinocytes and human dermal fibroblasts. International Journal of Molecular Sciences 2020;21(11):3981.
  38. Park HW, Cho SY, Kim HH, Yun BS, Kim JU, Lee SJ, Park J. Enantioselective induction of SIRT1 gene by syringaresinol from Panax ginseng berry and Acanthopanax senticosus Harms stem. Bioorganic & Medicinal Chemistry Letters 2015;25(2):307-9. https://doi.org/10.1016/j.bmcl.2014.11.045
  39. Paterno J, Vial IN, Wong VW, Rustad KC, Sorkin M, Shi Y, Bhatt KA, Thangarajah H, Glotzbach JP, Gurtner GCJWR, et al. Akt-mediated Mechanotransduction in Murine Fibroblasts During Hypertrophic Scar Formation, 19;2011. p. 49-58. 1. https://doi.org/10.1111/j.1524-475X.2010.00643.x
  40. Penn JW, Grobbelaar AO, Kjjijob Rolfe, trauma. The Role of the TGF-β Family in Wound Healing. Burns and Scarring: A Review 2012;2(1):18.
  41. Pettet G, Byrne H, McElwain D, Norbury J. A model of wound-healing angiogenesis in soft tissue. Mathematical Biosciences 1996;136(1):35-63. https://doi.org/10.1016/0025-5564(96)00044-2
  42. Porter S. The role of the fibroblast in wound contraction and healing. WOUNDS UK 2007;3(1):33.
  43. Proksch E, Brandner JM, Jensen JM. The skin: an indispensable barrier. Experimental Dermatology 2008;17(12):1063-72. https://doi.org/10.1111/j.1600-0625.2008.00786.x
  44. Qing C. The molecular biology in wound healing & non-healing wound. Chinese Journal of Traumatology 2017;20(4):189-93. https://doi.org/10.1016/j.cjtee.2017.06.001
  45. Rinkevich Y, Walmsley GG, Hu MS, Maan ZN, Newman AM, Drukker M, Januszyk M, Krampitz GW, Gurtner GC, Lorenz HPJS. Identification and Isolation of a Dermal Lineage with Intrinsic Fibrogenic Potential, 348;2015aaa2151. 6232.
  46. Schultz GS, Davidson JM, Kirsner RS, Bornstein P, Herman IM. Dynamic reciprocity in the wound microenvironment. Wound Repair and Regeneration 2011;19(2):134-48. https://doi.org/10.1111/j.1524-475X.2011.00673.x
  47. Shao Z-H, Xie J-T, Hoek TLV, Mehendale S, Aung H, Li C-Q, Qin Y, Schumacker PT, Becker LB, Yuan C-S. Antioxidant effects of American ginseng berry extract in cardiomyocytes exposed to acute oxidant stress. Biochimica et Biophysica Acta (BBA)-General Subjects 2004;1670(3):165-71. https://doi.org/10.1016/j.bbagen.2003.12.001
  48. Shen T, Duan C, Chen B, Li M, Ruan Y, Xu D, Shi D, Yu D, Li J, Wang C. Tremella fuciformis polysaccharide suppresses hydrogen peroxide-triggered injury of human skin fibroblasts via upregulation of SIRT1. Molecular Medicine Reports 2017;16(2):1340-6. https://doi.org/10.3892/mmr.2017.6754
  49. Shi W, Wang Y, Li J, Zhang H, Ding L. Investigation of ginsenosides in different parts and ages of Panax ginseng. Food Chemistry 2007;102(3):664-8. https://doi.org/10.1016/j.foodchem.2006.05.053
  50. Shin HR, Kim JY, Yun TK, Morgan G, Vainio H. The cancer-preventive potential of Panax ginseng: a review of human and experimental evidence. Cancer Causes & Control 2000;11(6):565-76.
  51. Singer AJ, Clark RA. Cutaneous wound healing. New England Journal of Medicine 1999;341(10):738-46. https://doi.org/10.1056/NEJM199909023411006
  52. Song J, Jung KJ, Yang MJ, Han SC, Lee K. Assessment of acute and repeated pulmonary toxicities of oligo(2-(2-ethoxy)ethoxyethyl guanidium chloride in mice. Toxicol Res 2021;37(1):99-113. https://doi.org/10.1007/s43188-020-00058-x.
  53. Vidal Yucha SE, Tamamoto KA, Nguyen H, Cairns DM, Kaplan DL. Human skin equivalents demonstrate need for neuro-immuno-cutaneous system. Advanced Biosystems 2019;3(1):1800283.
  54. Weeraratna AT, Jiang Y, Hostetter G, Rosenblatt K, Duray P, Bittner M, Trent JM. Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma. Cancer Cell 2002;1(3):279-88. https://doi.org/10.1016/S1535-6108(02)00045-4
  55. Werner S, Krieg T, Smola H. Keratinocyte-fibroblast interactions in wound healing. Journal of Investigative Dermatology 2007;127(5):998-1008. https://doi.org/10.1038/sj.jid.5700786
  56. Wilkinson HN, Kidd AS, Roberts ER, Hardman MJ. Human ex vivo wound model and whole-mount staining approach to accurately evaluate skin repair. JoVE 2021;168:e62326.
  57. Wong VW, Longaker MT. Gurtner GC Soft tissue mechanotransduction in wound healing and fibrosis. Seminars in Cell & Developmental Biology 2012;9:981-6. Elsevier. https://doi.org/10.1016/j.semcdb.2012.09.010
  58. Woodley DT, O'Keefe EJ, Prunieras M. Cutaneous wound healing: a model for cell-matrix interactions. Journal of the American Academy of Dermatology 1985;12(2):420-33. https://doi.org/10.1016/S0190-9622(85)80005-0
  59. Yuan H-D, Kim JT, Kim SH, Chung SH. Ginseng and diabetes: the evidences from in vitro, animal and human studies. Journal of Ginseng Research 2012;36(1):27.