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http://dx.doi.org/10.1016/j.jgr.2020.12.003

Enhancement of skin barrier and hydration-related molecules by protopanaxatriol in human keratinocytes  

Lee, Jeong-Oog (Department of Aerospace Information Engineering, Bio-Inspired Aerospace Information Laboratory, Konkuk University)
Hwang, So-Hyeon (Department of Integrative Biotechnology, Sungkyunkwan University)
Shen, Ting (Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University)
Kim, Ji Hye (Department of Integrative Biotechnology, Sungkyunkwan University)
You, Long (Department of Integrative Biotechnology, Sungkyunkwan University)
Hu, Weicheng (Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University)
Cho, Jae Youl (Department of Integrative Biotechnology, Sungkyunkwan University)
Publication Information
Journal of Ginseng Research / v.45, no.2, 2021 , pp. 354-360 More about this Journal
Abstract
Background: Protopanaxatriol (PPT) is a secondary intestinal metabolite of ginsenoside in ginseng. Although the effects of PPT have been reported in various diseases including cancer, diabetes and inflammatory diseases, the skin protective effects of PPT are poorly understood. Methods: HaCaT cells were treated with PPT in a dose-dependent manner. mRNA and protein levels which related to skin barrier and hydration were detected compared with retinol. Luciferase assay was performed to explore the relative signaling pathway. Western blot was conducted to confirm these pathways and excavated further signals. Results: PPT enhanced the expression of filaggrin (FLG), transglutaminase (TGM)-1, claudin, occludin and hyaluronic acid synthase (HAS) -1, -2 and -3. The mRNA expression levels of FLG, TGM-1, HAS-1 and HAS-2 were suppressed under NF-κB inhibition. PPT significantly augmented NF-κB-luc activity and upregulated Src/AKT/NF-κB signaling. In addition, PPT also increased phosphorylation of the mitogen-activated protein kinases (MAPKs) ERK, JNK and p38 and upstream MAPK activators (MEK and MKK). Furthermore, transcriptional activity of AP-1 and CREB, which are downstream signaling targets of MAPK, was enhanced by PPT. Conclusion: PPT improves skin barrier function and hydration through Src/AKT/NF-κB and MAPK signaling. Therefore, PPT may be a valuable component for cosmetics or treating skin disorders.
Keywords
protopanaxatriol; skin protection; $NF-{\kappa}B$; AP-1; CREB;
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1 Baek KS, Yi YS, Son YJ, Jeong D, Sung NY, Aravinthan A, Kim JH, Cho JY. Comparison of anticancer activities of Korean Red Ginseng-derived fractions. J Ginseng Res 2017;41:386-91.   DOI
2 Boury-Jamot M, Daraspe J, Bonte F, Perrier E, Schnebert S, Dumas M, Verbavatz JM. Skin aquaporins: function in hydration, wound healing, and skin epidermis homeostasis. Handb Exp Pharmacol 2009:205-17.
3 Proksch E, Lachapelle JM. The management of dry skin with topical emollients-recent perspectives. J Dtsch Dermatol Ges 2005;3:768-74.   DOI
4 Kubo A, Nagao K, Amagai M. Epidermal barrier dysfunction and cutaneous sensitization in atopic diseases. J Clin Invest 2012;122:440-7.   DOI
5 Seguchi T, Cui CY, Kusuda S, Takahashi M, Aisu K, Tezuka T. Decreased expression of filaggrin in atopic skin. Arch Dermatol Res 1996;288:442-6.   DOI
6 Itano N, Kimata K. Mammalian hyaluronan synthases. IUBMB Life 2002;54:195-9.   DOI
7 Nakai K, Yoneda K, Hosokawa Y, Moriue T, Presland RB, Fallon PG, Kabashima K, Kosaka H, Kubota Y. Reduced expression of epidermal growth factor receptor, E-cadherin, and occludin in the skin of flaky tail mice is due to filaggrin and loricrin deficiencies. Am J Pathol 2012;181:969-77.   DOI
8 Tammi R, Ripellino JA, Margolis RU, Tammi M. Localization of epidermal hyaluronic acid using the hyaluronate binding region of cartilage proteoglycan as a specific probe. J Invest Dermatol 1988;90:412-4.   DOI
9 Turino GM, Cantor JO. Hyaluronan in respiratory injury and repair. Am J Respir Crit Care Med 2003;167:1169-75.   DOI
10 Prehm P. Hyaluronate is synthesized at plasma membranes. Biochem J 1984;220:597-600.   DOI
11 Feldman GJ, Mullin JM, Ryan MP. Occludin: structure, function and regulation. Adv Drug Deliv Rev 2005;57:883-917.   DOI
12 Basler K, Bergmann S, Heisig M, Naegel A, Zorn-Kruppa M, Brandner JM. The role of tight junctions in skin barrier function and dermal absorption. J Control Release 2016;242:105-18.   DOI
13 Brandner JM. Importance of tight junctions in relation to skin barrier function. Curr Probl Dermatol 2016;49:27-37.   DOI
14 Tsukita S, Furuse M. Occludin and claudins in tight-junction strands: leading or supporting players? Trends Cell Biol 1999;9:268-73.   DOI
15 Sandilands A, Sutherland C, Irvine AD, McLean WH. Filaggrin in the frontline: role in skin barrier function and disease. J Cell Sci 2009;122:1285-94.   DOI
16 Dale BA, Ling SY. Immunologic cross-reaction of stratum corneum basic protein and a keratohyalin granule protein. J Invest Dermatol 1979;72:257-61.   DOI
17 Steinert PM, Marekov LN. The proteins elafin, filaggrin, keratin intermediate filaments, loricrin, and small proline-rich proteins 1 and 2 are isodipeptide cross-linked components of the human epidermal cornified cell envelope. J Biol Chem 1995;270:17702-11.   DOI
18 Thacher SM, Rice RH. Keratinocyte-specific transglutaminase of cultured human epidermal cells: relation to cross-linked envelope formation and terminal differentiation. Cell 1985;40:685-95.   DOI
19 Harding CR, Watkinson A, Rawlings AV, Scott IR. Dry skin, moisturization and corneodesmolysis. Int J Cosmet Sci 2000;22:21-52.   DOI
20 Rawlings AV, Scott IR, Harding CR, Bowser PA. Stratum corneum moisturization at the molecular level. J Invest Dermatol 1994;103:731-41.   DOI
21 Blank IH. Factors which influence the water content of the stratum corneum. J Invest Dermatol 1952;18:433-40.   DOI
22 Matoltsy AG, Matoltsy MN. The membrane protein of horny cells. J Invest Dermatol 1966;46:127-9.   DOI
23 Juhlin L. Hyaluronan in skin. J Intern Med 1997;242:61-6.   DOI
24 Robinson NA, Lapic S, Welter JF, Eckert RL. S100A11, S100A10, annexin I, desmosomal proteins, small proline-rich proteins, plasminogen activator inhibitor-2, and involucrin are components of the cornified envelope of cultured human epidermal keratinocytes. J Biol Chem 1997;272:12035-46.   DOI
25 Matthews CP, Colburn NH, Young MR. AP-1 a target for cancer prevention. Curr Cancer Drug Targets 2007;7:317-24.   DOI
26 Oh GS, Pae HO, Choi BM, Seo EA, Kim DH, Shin MK, Kim JD, Kim JB, Chung HT. 20(S)-Protopanaxatriol, one of ginsenoside metabolites, inhibits inducible nitric oxide synthase and cyclooxygenase-2 expressions through inactivation of nuclear factor-kappaB in RAW 264.7 macrophages stimulated with lipopolysaccharide. Cancer Lett 2004;205:23-9.   DOI
27 Schonthaler HB, Guinea-Viniegra J, Wagner EF. Targeting inflammation by modulating the Jun/AP-1 pathway. Ann Rheum Dis 2011;70(Suppl 1). i109-112.   DOI
28 Agre P. The aquaporin water channels. Proc Am Thorac Soc 2006;3:5-13.   DOI
29 Kim JH, Yi YS, Kim MY, Cho JY. Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases. J Ginseng Res 2017;41:435-43.   DOI
30 Jeong D, Lee J, Park SH, Kim YA, Park BJ, Oh J, Sung GH, Aravinthan A, Kim JH, Kang H, et al. Antiphotoaging and antimelanogenic effects of penthorum chinense pursh ethanol extract due to antioxidant- and autophagy-inducing properties. Oxid Med Cell Longev 2019;2019:9679731.   DOI
31 Peng S, Zhang Y, Zhang J, Wang H, Ren B. ERK in learning and memory: a review of recent research. Int J Mol Sci 2010;11:222-32.   DOI
32 Yang WS, Yi YS, Kim D, Kim MH, Park JG, Kim E, Lee SY, Yoon K, Kim JH, Park J, et al. Nuclear factor kappa-B- and activator protein-1-mediated immunostimulatory activity of compound K in monocytes and macrophages. J Ginseng Res 2017;41:298-306.   DOI
33 Baek KS, Yi YS, Son YJ, Yoo S, Sung NY, Kim Y, Hong S, Aravinthan A, Kim JH, Cho JY. In vitro and in vivo anti-inflammatory activities of Korean Red Ginseng-derived components. J Ginseng Res 2016;40:437-44.   DOI
34 Shaywitz AJ, Greenberg ME. CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu Rev Biochem 1999;68:821-61.   DOI
35 Mechin MC, Enji M, Nachat R, Chavanas S, Charveron M, Ishida-Yamamoto A, Serre G, Takahara H, Simon M. The peptidylarginine deiminases expressed in human epidermis differ in their substrate specificities and subcellular locations. Cell Mol Life Sci 2005;62:1984-95.   DOI
36 Ishida-Yamamoto A, Senshu T, Eady RA, Takahashi H, Shimizu H, Akiyama M, Iizuka H. Sequential reorganization of cornified cell keratin filaments involving filaggrin-mediated compaction and keratin 1 deimination. J Invest Dermatol 2002;118:282-7.   DOI
37 Zhang Y, Yu L, Cai W, Fan S, Feng L, Ji G, Huang C. Protopanaxatriol, a novel PPARgamma antagonist from Panax ginseng, alleviates steatosis in mice. Sci Rep 2014;4:7375.   DOI
38 Choi JW, Kwon SH, Huh CH, Park KC, Youn SW. The influences of skin viscoelasticity, hydration level and aging on the formation of wrinkles: a comprehensive and objective approach. Skin Res Technol 2013;19. e349-355.   DOI
39 Papakonstantinou E, Roth M, Karakiulakis G. Hyaluronic acid: a key molecule in skin aging. Dermatoendocrinol 2012;4:253-8.   DOI
40 Reed RK, Laurent UB, Fraser JR, Laurent TC. Removal rate of [3H]hyaluronan injected subcutaneously in rabbits. Am J Physiol 1990;259:H532-5.
41 Oh HA, Kim DE, Choi HJ, Kim NJ, Kim DH. Anti-fatigue effects of 20(S)-Protopanaxadiol and 20(S)-Protopanaxatriol in mice. Biol Pharm Bull 2015;38:1415-9.   DOI
42 Jang S, Lim Y, Valacchi G, Sorn S, Park H, Park NY, Lee M. Preventive effects of protopanaxadiol and protopanaxatriol ginsenosides on liver inflammation and apoptosis in hyperlipidemic apoE KO mice. Genes Nutr 2012;7:319-29.   DOI
43 Deng J, Liu Y, Duan Z, Zhu C, Hui J, Mi Y, Ma P, Ma X, Fan D, Yang H. Protopanaxadiol and protopanaxatriol-type saponins ameliorate glucose and lipid metabolism in type 2 diabetes mellitus in high-fat diet/streptozocin-induced mice. Front Pharmacol 2017;8:506.   DOI
44 Chen XJ, Zhang XJ, Shui YM, Wan JB, Gao JL. Anticancer activities of protopanaxadiol- and protopanaxatriol-type ginsenosides and their metabolites. Evid Based Complement Alternat Med 2016;2016:5738694.
45 Oh SJ, Kim K, Lim CJ. Photoprotective properties of 20(S)-protopanaxatriol, an aglycone of ginseng saponins: protection from ultraviolet-B radiation-induced oxidative stress in human epidermal keratinocytes. Mol Med Rep 2016;14:2839-45.   DOI
46 Ben-Neriah Y, Karin M. Inflammation meets cancer, with NF-kappaB as the matchmaker. Nat Immunol 2011;12:715-23.   DOI
47 Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248-54.   DOI
48 Rauhala L, Jokela T, Karna R, Bart G, Takabe P, Oikari S, Tammi MI, Pasonen-Seppanen S, Tammi RH. Extracellular ATP activates hyaluronan synthase 2 (HAS2) in epidermal keratinocytes via P2Y2, Ca(2+) signaling, and MAPK pathways. Biochem J 2018;475:1755-72.   DOI
49 Otsuka A, Doi H, Egawa G, Maekawa A, Fujita T, Nakamizo S, Nakashima C, Nakajima S, Watanabe T, Miyachi Y, et al. Possible new therapeutic strategy to regulate atopic dermatitis through upregulating filaggrin expression. J Allergy Clin Immunol 2014;133:139-146 e131-110.   DOI