DOI QR코드

DOI QR Code

Glycosyl flavones from Humulus japonicus suppress MMP-1 production via decreasing oxidative stress in UVB irradiated human dermal fibroblasts

  • Nam, Eui Jeong (New Product Development Team, COSMAXNBT) ;
  • Yoo, Gyhye (Smart Farm Research Center, Korea Institute of Science and Technology (KIST) Gangneung Institute) ;
  • Lee, Joo Young (Natural Products Research Center, Korea Institute of Science and Technology (KIST) Gangneung Institute) ;
  • Kim, Myungsuk (Smart Farm Research Center, Korea Institute of Science and Technology (KIST) Gangneung Institute) ;
  • Jhin, Changho (Smart Farm Research Center, Korea Institute of Science and Technology (KIST) Gangneung Institute) ;
  • Son, Yang-Ju (Smart Farm Research Center, Korea Institute of Science and Technology (KIST) Gangneung Institute) ;
  • Kim, Sun Young (Smart Farm Research Center, Korea Institute of Science and Technology (KIST) Gangneung Institute) ;
  • Jung, Sang Hoon (Natural Products Research Center, Korea Institute of Science and Technology (KIST) Gangneung Institute) ;
  • Nho, Chu Won (Smart Farm Research Center, Korea Institute of Science and Technology (KIST) Gangneung Institute)
  • Received : 2019.10.22
  • Accepted : 2020.01.07
  • Published : 2020.07.31

Abstract

Exposure to Ultraviolet (UV) light induces photoaging of skin, leading to wrinkles and sunburn. The perennial herb Humulus japonicus, widely distributed in Asia, is known to have anti-inflammatory, antimicrobial, and antioxidant effects. However, the physiological activities of isolated compounds from H. japonicus have rarely been investigated. This study focused on the isolation of active compounds from H. japonicus and the evaluation of their effects on photoaging in UVB-irradiated human fibroblast (Hs68) cells. When the extract and four fractions of H. japonicus were treated respectively in UVB-irradiated Hs68 cells to investigate anti-photoaging effects, the ethyl acetate (EtOAc) fraction showed the strongest inhibitory effect on MMP1 secretion. From EtOAc fraction, we isolated luteolin-8-C-glucoside (1), apigenin-8-C-glucoside (2), and luteolin-7-O-glucoside (3). These compounds suppressed UVB-induced MMP-1 production by inhibiting the phosphorylation of the mitogen-activated protein kinases (MAPKs) and activator protein-1 (AP-1). When the antioxidant activity of the compounds were estimated by conducting western blot, calculating the bond dissociation energies of the O-H bond (BDE) at different grade, and measuring radical scavenging activity, we found luteolin-8-C-glucoside (1) showed the strongest activity on the suppression of UVB-induced photoaging. These results demonstrate the inhibitory effect of three flavone glycosides derived from H. japonicus on MMP-1 production, MAPK and AP-1 signaling, and oxidative stress; this could prove useful in suppressing UVB induced photoaging.

Keywords

References

  1. Bosch R, Philips N, Suarez-Perez JA et al (2015) Mechanisms of photoaging and cutaneous photocarcinogenesis, and photoprotective strategies with phytochemicals. Antioxidants (Basel) 4, 248-268 https://doi.org/10.3390/antiox4020248
  2. Fisher GJ, Wang ZQ, Datta SC et al (1997) Pathophysiology of premature skin aging induced by ultraviolet light. N Engl J Med 337, 1419-1428 https://doi.org/10.1056/NEJM199711133372003
  3. Jenkins G (2002) Molecular mechanisms of skin ageing. Mech Ageing Dev 123, 801-810 https://doi.org/10.1016/S0047-6374(01)00425-0
  4. Narayanan DL, Saladi RN and Fox JL (2010) Ultraviolet radiation and skin cancer. Int J Dermatol 49, 978-986 https://doi.org/10.1111/j.1365-4632.2010.04474.x
  5. Quan T, Qin Z, Xia W et al (2009) Matrix-degrading metalloproteinases in photoaging. J Investig Dermatol Symp Proc 14, 20-24 https://doi.org/10.1038/jidsymp.2009.8
  6. Fisher GJ and Voorhees JJ (1998) Molecular mechanisms of photoaging and its prevention by retinoic acid: ultraviolet irradiation induces MAP kinase signal transduction cascades that induce Ap-1-regulated matrix metalloproteinases that degrade human skin in vivo. J Investig Dermatol Symp Proc 3, 61-68 https://doi.org/10.1038/jidsp.1998.15
  7. Naya Y and Kotake M (1970) Constituents of Hops. 5. volatile composition of humulus-japonicus sieb et zucc. Bull Chem Soc Jpn 43, 3594-3596 https://doi.org/10.1246/bcsj.43.3594
  8. Hwang SY, Jung HJ, Jang WS et al (2009) Antiinflammaory effects of the MeOH extract of Humulus japonicus in vitro. J Korean Med Ophthalmol Otolaryngol Dermatol 22, 71-79
  9. Lee YR, Kim KY, Lee SH et al (2012) Antioxidant and antitumor activities of methanolic extracts from Humulus japonicus. Korean J Food & Nutr 25, 357-361 https://doi.org/10.9799/ksfan.2012.25.2.357
  10. Sung B, Chung JW, Bae HR, Choi JS, Kim CM and Kim ND (2015) Humulus japonicus extract exhibits antioxidative and anti-aging effects via modulation of the AMPK-SIRT1 pathway. Exp Ther Med 9, 1819-1826 https://doi.org/10.3892/etm.2015.2302
  11. Yu BC, Yang MC, Lee KH et al (2007) Norsesquiterpene and steroid constituents of Humulus japonicus. Nat Prod Sci 13, 332-336
  12. Yu BC, Yang MC, Lee KH et al (2007) Two new phenolic constituents of Humulus japonicus and their cytotoxicity test in vitro. Arch Pharm Res 30, 1471-1475 https://doi.org/10.1007/BF02977373
  13. Kim JE, Shin MH and Chung JH (2013) Epigallocatechin-3-gallate prevents heat shock-induced MMP-1 expression by inhibiting AP-1 activity in human dermal fibroblasts. Arch Dermatol Res 305, 595-602 https://doi.org/10.1007/s00403-013-1393-y
  14. Amic D and Lucic B (2010) Reliability of bond dissociation enthalpy calculated by the PM6 method and experimental TEAC values in antiradical QSAR of flavonoids. Bioorg Med Chem 18, 28-35 https://doi.org/10.1016/j.bmc.2009.11.015
  15. Amic D, Stepanic V, Lucic B et al (2013) PM6 study of free radical scavenging mechanisms of flavonoids: why does O-H bond dissociation enthalpy effectively represent free radical scavenging activity? J Mol Model 19, 2593-2603 https://doi.org/10.1007/s00894-013-1800-5
  16. Zhang HY, Sun YM and Wang XL (2003) Substituent effects on O--H bond dissociation enthalpies and ionization potentials of catechols: a DFT study and its implications in the rational design of phenolic antioxidants and elucidation of structure-activity relationships for flavonoid antioxidants. Chemistry 9, 502-508 https://doi.org/10.1002/chem.200390052
  17. American Cancer Society, Cancer Facts & Figures 2019. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2019/cancer-facts-and-figures-2019.pdf
  18. Sim GS, Lee BC, Cho HS et al (2007) Structure activity relationship of antioxidative property of flavonoids and inhibitory effect on matrix metalloproteinase activity in UVA-irradiated human dermal fibroblast. Arch Pharm Res 30, 290-298 https://doi.org/10.1007/BF02977608
  19. Rittie L and Fisher GJ (2002) UV-light-induced signal cascades and skin aging. Ageing Res Rev 1, 705-720 https://doi.org/10.1016/S1568-1637(02)00024-7
  20. Benavente-Garcia O, Castillo J, Lorente J et al (2000) Antioxidant activity of phenolics extracted from Olea europaea L. leaves. Food Chem 68, 457-462 https://doi.org/10.1016/S0308-8146(99)00221-6
  21. Perveen S, El-Shafae AM, Al-Taweel A et al (2011) Antioxidant and urease inhibitory C-glycosylflavonoids from Celtis africana. J Asian Nat Prod Res 13, 799-804 https://doi.org/10.1080/10286020.2011.593171
  22. Praveena R, Sadasivam K, Deepha V et al (2014) Antioxidant potential of orientin: A combined experimental and DFT approach. J Mol Struct 1061, 114-123 https://doi.org/10.1016/j.molstruc.2014.01.002
  23. Praveena R, Sadasivam K, Kumaresan R et al (2013) Experimental and DFT studies on the antioxidant activity of a C-glycoside from Rhynchosia capitata. Spectrochim Acta A Mol Biomol Spectrosc 103, 442-452 https://doi.org/10.1016/j.saa.2012.11.001
  24. Wang Y, Xiao J, Suzek TO et al (2009) PubChem: a public information system for analyzing bioactivities of small molecules. Nucleic Acids Res 37, W623-W633 https://doi.org/10.1093/nar/gkp456
  25. O'Boyle NM, Banck M, James CA et al (2011) Open Babel: An open chemical toolbox. J Cheminform 3, 1 https://doi.org/10.1186/1758-2946-3-1
  26. Stewart JJ (2013) Optimization of parameters for semiempirical methods VI: more modifications to the NDDO approximations and re-optimization of parameters. J Mol Model 19, 1-32 https://doi.org/10.1007/s00894-012-1667-x
  27. Brand-Williams W, Cuvelier ME and Berset C (1995) Use of a free-radical method to evaluate antioxidant activity. Food Sci Technol-Leb 28, 25-30 https://doi.org/10.1016/S0023-6438(95)80008-5