Abstract
Ultraviolet B (UVB)-induced cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-1 are representative markers for skin inflammation and photoaging, respectively. To evaluate compounds that may counteract the effects of UVB-induced skin damage, we developed an immortalized human keratinocyte (HaCaT) cell line with an MMP-1 reporter construct. Among the 30 botanical extracts screened, we selected Ephedra sinica extract (ESE) as a promising candidate and confirmed that ESE significantly suppresses UVB-induced COX-2 and MMP-1 expression in HaCaT cells. Treatment with ESE also potently suppressed UVB-induced ERK1/2 phosphorylation, as well as UVB-induced MEK1/2 and Raf phosphorylation in HaCaT cells. These findings suggest that our MMP-1 reporter system can be used to evaluate compounds with anti-inflammatory and anti-photoaging effects. We also report that ESE has potent suppressive effects against COX-2 and MMP-1 expression, which occurs via downregulation of Raf/MEK1/2/ERK1/2 phosphorylation.
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Jung SK, Lee KW, Byun S, Kang NJ, Lim SH, Heo YS, Bode AM, Bowden GT, Lee HJ, Dong Z. Myricetin suppresses UVB-induced skin cancer by targeting Fyn. Cancer Res. 68: 6021–6029 (2008)
Fisher GJ. The pathophysiology of photoaging of the skin. Cutis 75: 5–8; discussion 8–9 (2005)
Fisher GJ, Datta SC, Talwar HS, Wang ZQ, Varani J, Kang S, Voorhees JJ. Molecular basis of sun-induced premature skin ageing and retinoid antagonism. Nature 379: 335–339 (1996)
Schäfer M, Werner S. Nrf2—A regulator of keratinocyte redox signaling. Free Radic. Biol. Med. 88: 243–252 (2015)
Eferl R, Wagner EF. AP-1: a double-edged sword in tumorigenesis. Nat. Rev. Cancer 3: 859–868 (2003)
Pittayapruek P, Meephansan J, Prapapan O, Komine M, Ohtsuki M. Role of matrix metalloproteinases in photoaging and photocarcinogenesis. Int. J. Mol. Sci. 17: 868 (2016)
Wang X, Zheng S. Whole fossil plants of Ephedra and their implications on the morphology, ecology and evolution of Ephedraceae (Gnetales). Chinese Sci. Bull. 55: 1511–1519 (2010)
Wei P, Huo H-l, Ma Q-h, Li H-c, Xing X-f, Tan X-m, Luo J-b. Pharmacokinetic comparisons of five ephedrine alkaloids following oral administration of four different Mahuang–Guizhi herb-pair aqueous extracts ratios in rats. J. Ethnopharmacology 155: 642–648 (2014)
Kim B-S, Song M-y, Kim H. The anti-obesity effect of Ephedra sinica through modulation of gut microbiota in obese Korean women. J. Ethnopharmacology 152: 532–539 (2014)
Lv M, Sun J, Wang M, Huang W, Fan H, Xu F, Zhang Z. GC–MS based metabolomics study of stems and roots of Ephedra sinica. J. Pharmaceut. Biomed. 114: 49–52 (2015)
Tseng YL, Hsu H-R, Kuo F-H, Shieh M-H, Chang C-F. Ephedrines in over-the-counter cold medicines and urine specimens collected during sport competitions. J. Anal. Toxicol. 27: 359–365 (2003)
Lee M, Cheng B, Che C, Hsieh D. Cytotoxicity assessment of Ma-huang (Ephedra) under different conditions of preparation. Toxicol. Sci. 56: 424–430 (2000)
Kim MK, Shin JM, Eun HC, Chung JH. The role of p300 histone acetyltransferase in UV-induced histone modifications and MMP-1 gene transcription. PLoS One 4: e4864 (2009)
Jung SK, Ha SJ, Kim YA, Lee J, Lim TG, Kim YT, Lee NH, Park JS, Yeom MH, Lee HJ. MLK3 is a novel target of dehydroglyasperin D for the reduction in UVB‐induced COX‐2 expression in vitro and in vivo. J. Cell. Mol. Med. 19: 135–142 (2015)
Huang C, Ma WY, Hanenberger D, Cleary MP, Bowden GT, Dong Z. Inhibition of ultraviolet B-induced activator protein-1 (AP-1) activity by aspirin in AP-1-luciferase transgenic mice. J. Biol. Chem. 272: 26325–26331 (1997)
Kim HJ, Cho YD, Leem KH, Lee DN, Kim EH, Kim MG, Kim DK, Shin TY, Boo Y, Lee JH, Kim HK. Effects of Ephedrae Herba on melanogenesis and gene expression profiles using cDNA microarray in b16 melanocytes. Phytotherapy Res. 20: 748–754 (2006)
Yeom MJ, Lee HC, Kim GH, Lee HJ, Shim I, Oh SK, Kang SK, Hahm DH. Anti-arthritic effects of Ephedra sinica STAPF herb-acupuncture: inhibition of lipopolysaccharide-induced inflammation and adjuvant-induced polyarthritis. J. Pharmacol. Sci. 100: 41–50 (2006)
Wang QH, Shu ZP, Xing N, Xu BQ, Wang CF, Sun GB, Sun XB, Kuang HX. A pure polysaccharide from Ephedra sinica treating on arthritis and inhibiting cytokines expression. Int. J. Biol. Macromol. 86: 177–188 (2016)
Roberts PJ, Der CJ. Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 26: 3291–3310 (2007)
Ha SJ, Lee J, Kim H, Song K-M, Lee NH, Kim YE, Lee H, Kim YH, Jung SK. Preventive effect of Rhus javanica extract on UVB-induced skin inflammation and photoaging. J. Funct. Foods 27: 589–599 (2016)
Jung SK, Lee KW, Kim HY, Oh MH, Byun S, Lim SH, Heo YS, Kang NJ, Bode AM, Dong Z, Lee HJ. Myricetin suppresses UVB-induced wrinkle formation and MMP-9 expression by inhibiting Raf. Biochem. Pharmacol. 79: 1455–1461 (2010)
Jung SK, Ha SJ, Jung CH, Kim YT, Lee HK, Kim MO, Lee MH, Mottamal M, Bode AM, Lee KW, Dong Z. Naringenin targets ERK2 and suppresses UVB-induced photoaging. J. Cell. Mol. Med. 20: 909–919 (2016)
Bode AM, Dong Z. Mitogen-activated protein kinase activation in UV-induced signal transduction. Sci. STKE 2003: RE2 (2003)
Basbous J, Chalbos D, Hipskind R, Jariel-Encontre I, Piechaczyk M. Ubiquitin-independent proteasomal degradation of Fra-1 is antagonized by Erk1/2 pathway-mediated phosphorylation of a unique C-terminal destabilizer. Mol. Cell. Biol. 27: 3936–3950 (2007)
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This research was supported by a grant from the Korea Food Research Institute, Republic of Korea.
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Ha, S.J., Lee, C.J. & Jung, S.K. Preventive effect of Ephedra sinica extract on UVB-induced COX-2 and MMP-1 expression. Food Sci Biotechnol 27, 1157–1163 (2018). https://doi.org/10.1007/s10068-018-0331-3
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DOI: https://doi.org/10.1007/s10068-018-0331-3