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4-Hexylresorcinol induced angiogenesis potential in human endothelial cells

  • Kim, Min-Keun (Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University, and Institute of Oral Science) ;
  • Kim, Seong-Gon (Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University, and Institute of Oral Science) ;
  • Lee, Suk Keun (Department of Oral Pathology, College of Dentistry, Gangneung-Wonju National University, and Institute of Oral Science)
  • Received : 2020.03.27
  • Accepted : 2020.05.11
  • Published : 2020.12.31

Abstract

Background: 4-Hexylresorcinol (4HR) is able to increase angiogenesis. However, its molecular mechanism in the human endothelial cells has not been clarified. Methods: As endothelial cells are important in angiogenesis, we treated the human umbilical vein endothelial cells (HUVECs) with 4HR and investigated protein expressional changes by immunoprecipitation high-performance liquid chromatography (IP-HPLC) using 96 antisera. Results: Here, we found that 4HR upregulated transforming growth factor-β (TGF-β)/SMAD/vascular endothelial growth factor (VEGF) signaling, RAF-B/ERK and p38 signaling, and M2 macrophage polarization pathways. 4HR also increased expression of caspases and subsequent cellular apoptosis. Mechanistically, 4HR increased TGF-β1 production and subsequent activation of SMADs/VEGFs, RAF-B/ERK and p38 signaling, and M2 macrophage polarization. Conclusion: Collectively, 4HR activates TGF-β/SMAD/VEGF signaling in endothelial cells and induced vascular regeneration and remodeling for wound healing.

Keywords

Acknowledgement

This study was carried out with the support of "Cooperative Research Program for Agriculture Science and Technology Development (Project no. PJ01313902)" Rural Development Administration, Republic of Korea.

References

  1. McConnell VF (1953) Hlasiwetz and Barth - pioneers in the structural aspects of plant products. J Chem Educ 30:380-385
  2. Wilson CO, Gisvold O, Doerge RF (1966) Textbook of organic medicinal and pharmaceutical chemistry, 5th edn. Lippincott, Philadelphia, PA, USA, pp 237-262
  3. He J, Zhu Q, Dong X, Pan H, Chen J, Zheng ZP (2017) Oxyresveratrol and ascorbic acid O/W microemulsion: preparation, characterization, antiisomerization and potential application as antibrowning agent on fresh-cut lotus root slices. Food Chem 214:269-276
  4. Darlow HM, Powell EO, Bale WR, Morris EJ (1958) Observations on the bactericidal action of hexyl resorcinol aerosols. J Hyg 56:108-124
  5. Brkic D (1956) Intestinal parasites: helminths; with special reference to newer antihelminthics. Srp Arh Celok Lek 84:1401-1416
  6. Ujiie T (1968) Experimental anticancer studies. XXXIV. Some compounds relating to 4-n-hexyl-6-(2-hydroxyphenyliminomethyl) resorcinol and their anticancer activity. Chem Pharm Bull 16:165-171
  7. Chevalier M, Sakarovitch C, Precheur I, Lamure J, Pouyssegur-Rougier V (2015) Antiseptic mouthwashes could worsen xerostomia in patients taking polypharmacy. Acta Odontol Scand 73:267-273
  8. Yen GC, Duh PD, Lin CW (2003) Effects of resveratrol and 4-hexylresorcinol on hydrogen peroxide-induced oxidative DNA damage in human lymphocytes. Free Radic Res 37:509-514
  9. Guandalini E, Ioppolo A, Mantovani A, Stacchini P, Giovannini C (1998) 4-Hexylresorcinol as inhibitor of shrimp melanosis: efficacy and residues studies; evaluation of possible toxic effect in a human intestinal in vitro model (Caco-2); preliminary safety assessment. Food Addit Contam 15:171-180
  10. Jo YY, Kim DW, Choi JY, Kim SG (2019) 4-Hexylresorcinol and silk sericin increase the expression of vascular endothelial growth factor via different pathways. Sci Rep 9:3448
  11. Liu Y, Zhang H, Yan L, Du W, Zhang M, Chen H, Zhang L, Li G, Li J, Dong Y, Zhu D (2018) MMP-2 and MMP-9 contribute to the angiogenic effect produced by hypoxia/15-HETE in pulmonary endothelial cells. J Mol Cell Cardiol 121:36-50
  12. Gresele P, Falcinelli E, Momi S (2008) Potentiation and priming of platelet activation: a potential target for antiplatelet therapy. Trends Pharmacol Sci 29:352-360
  13. Clarke NJ, Tomlinson AJ, Ohyagi Y, Younkin S, Naylor S (1998) Detection and quantitation of cellularly derived amyloid beta peptides by immunoprecipitation-HPLC-MS. FEBS letters 430:419-423
  14. Luo L, Shen L, Sun F, Ma Z (2013) Immunoprecipitation coupled with HPLC-MS/MS to discover the aromatase ligands from Glycyrrhiza uralensis. Food Chem 138:315-320
  15. Kim YS, Lee SK (2015) IP-HPLC analysis of human salivary protein complexes. Kor J Oral Maxillofac Pathol 39:615-622
  16. Kim SM, Eo MY, Cho YJ, Kim YS, Lee SK (2018) Immunoprecipitation high performance liquid chromatographic analysis of healing process in chronic suppurative osteomyelitis of the jaw. J Craniomaxillofac Surg 46:119-127
  17. Kim SM, Eo MY, Cho YJ, Kim YS, Lee SK (2017) Wound healing protein profiles in the postoperative exudate of bisphosphonate-related osteonecrosis of mandible. Eur Arch Otorhinolaryngol 274:3485-3495
  18. Kim SM, Eo MY, Cho YJ, Kim YS, Lee SK (2017) Differential protein expression in the secretory fluids of maxillary sinusitis and maxillary retention cyst. Eur Arch Otorhinolaryngol 274:215-222
  19. Kim MK, Yoon CS, Kim SG, Park YW, Lee SK (2019) Effects of 4-hexylresorcinol on protein expressions in RAW 264.7 cells as determined by immunoprecipitation high performance liquid chromatography. Sci Rep 9:3379
  20. Yoon CS, Kim MK, Kim YS, Lee SK (2018) In vitro protein expression changes in RAW 264.7 cells and HUVECs treated with dialyzed coffee extract by immunoprecipitation high performance liquid chromatography. Sci Rep 8:13841
  21. Kim SM, Jeong D, Kim MK, Lee SS, Lee SK (2017) Two different protein expression profiles of oral squamous cell carcinoma analyzed by immunoprecipitation high-performance liquid chromatography. World J Surg Oncol 15:151
  22. Yoon CS, Kim MK, Kim YS, Lee SK (2018) In vivo protein expression changes in mouse livers treated with dialyzed coffee extract as determined by IP-HPLC. Maxillofac Plast Reconstr Surg 40:44
  23. Choi KH, Kim DW, Lee SK, Kim SG, Kim TW (2020) The administration of 4-hexylresorcinol accelerates orthodontic tooth movement and increases the expression level of bone turnover markers in ovariectomized rats. Int J Mol Sci 21(4):1526
  24. Feng S, Song XH, Zeng CM (2012) Inhibition of amyloid fibrillation of lysozyme by phenolic compounds involves quinoprotein formation. FEBS letters 586:3951-3955
  25. Ahn J, Kim SG, Kim MK, Kim DW, Lee JH, Seok H, Choi JY (2016) Topical delivery of 4-hexylresorcinol promotes wound healing via tumor necrosis factor-alpha suppression. Burns 42:1534-1541
  26. Kang YJ, Noh JE, Lee MJ, Chae WS, Lee SY, Kim SG (2016) The effect of 4-hexylresorcinol on xenograft degradation in a rat calvarial defect model. Maxillofac Plastic Reconstr Surg 38:29
  27. Kim SG (2020) Immunomodulation for maxillofacial reconstructive surgery. Maxillofac Plast Reconstr Surg 42:5
  28. Kweon H, Kim SG, Choi JY (2014) Inhibition of foreign body giant cell formation by 4-hexylresorcinol through suppression of diacylglycerol kinase delta gene expression. Biomaterials 35(30):8576-8584
  29. Jo YY, Kweon H, Kim DW, Kim MK, Kim SG, Kim JY, Chae WS, Hong SP, Park YH, Lee SY, Choi JY (2017) Accelerated biodegradation of silk sutures through matrix metalloproteinase activation by incorporating 4-hexylresorcinol. Sci Rep 7:42441
  30. Song JY, Kim SG, Park NR, Choi JY (2018) Porcine bone incorporated with 4-hexylresorcinol increases new bone formation by suppression of the nuclear factor kappa B signaling pathway. J Craniofac Surg 29(7):1983-1990

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