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http://dx.doi.org/10.5021/ad.2018.30.6.653

Citron Essential Oils Alleviate the Mediators Related to Rosacea Pathophysiology in Epidermal Keratinocytes  

Jeon, Hyeon Woo (Department of Dermatology, Chonnam National University Medical School)
Na, Eui Young (Department of Dermatology, Chonnam National University Medical School)
Yun, Sook Jung (Department of Dermatology, Chonnam National University Medical School)
Lee, Seung-Chul (Department of Dermatology, Chonnam National University Medical School)
Lee, Jee-Bum (Department of Dermatology, Chonnam National University Medical School)
Publication Information
Annals of dermatology / v.30, no.6, 2018 , pp. 653-661 More about this Journal
Abstract
Background: Citron is well known for an abundance of antioxidative and anti-inflammatory ingredients such as vitamin C, polyphenol compounds, flavonoids, and limonoids. Objective: In this study, we aimed to evaluate the effects of citron essential oils on rosacea mediators in activated keratinocytes in vitro. Methods: Normal human epidermal keratinocytes (NHEKs) were stimulated with $1{\alpha}$, 25-dihydroxyvitamin $D_3$ ($VD_3$) and interleukin 33 (IL-33) with LL-37 to induce rosacea mediators such as kallikrein 5 (KLK5), cathelicidin, vascular endothelial growth factor (VEGF), and transient receptor potential vanilloid 1 (TRPV1). These mediators were analyzed by performing reverse-transcription polymerase chain reaction (PCR), quantitative real-time PCR, immunocytofluorescence and enzyme-linked immunosorbent assay after NHEKs were treated with citron seed and unripe citron essential oils. Results: The messenger RNA (mRNA) and protein levels of KLK5 and LL-37 induced by $VD_3$ were suppressed by citron seed and unripe citron essential oils. Furthermore, the mRNA and protein levels of VEGF and TRPV1 induced by IL-33 with LL-37 were also suppressed by citron essential oils. Conclusion: These results show that citron essential oils have suppressive effects on rosacea mediators in activated epidermal keratinocytes, which indicates that the citron essential oils may be valuable adjuvant therapeutic agents for rosacea.
Keywords
Citron essential oils; Rosacea;
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1 Sawamura M, Wu Y, Fujiwara C, Urushibata M. Inhibitory effect of yuzu essential oil on the formation of N-nitrosodimethylamine in vegetables. J Agric Food Chem 2005;53:4281-4287.   DOI
2 Yoo KM, Lee KW, Park JB, Lee HJ, Hwang IK. Variation in major antioxidants and total antioxidant activity of Yuzu (Citrus junos Sieb ex Tanaka) during maturation and between cultivars. J Agric Food Chem 2004;52:5907-5913.   DOI
3 Zou Z, Xi W, Hu Y, Nie C, Zhou Z. Antioxidant activity of citrus fruits. Food Chem 2016;196:885-896.   DOI
4 Hirota R, Roger NN, Nakamura H, Song HS, Sawamura M, Suganuma N. Anti-inflammatory Effects of limonene from yuzu (Citrus junos Tanaka) essential oil on eosinophils. J Food Sci 2010;75:H87-H92.   DOI
5 Crawford GH, Pelle MT, James WD. Rosacea: I. Etiology, pathogenesis, and subtype classification. J Am Acad Dermatol 2004;51:327-341.   DOI
6 Schwab VD, Sulk M, Seeliger S, Nowak P, Aubert J, Mess C, et al. Neurovascular and neuroimmune aspects in the pathophysiology of rosacea. J Investig Dermatol Symp Proc 2011;15:53-62.   DOI
7 Two AM, Del Rosso JQ. Kallikrein 5-mediated inflammation in rosacea: clinically relevant correlations with acute and chronic manifestations in rosacea and how individual treatments may provide therapeutic benefit. J Clin Aesthet Dermatol 2014;7:20-25.
8 Langeswaran K, Jagadeesan AJ, Revathy R, Balasubramanian MP. Chemotherapeutic efficacy of limonin against Aflatoxin B1 induced primary hepatocarcinogenesis in Wistar albino rats. Biomed Aging Pathol 2012;2:206-211.   DOI
9 Giamperi L, Fraternale D, Bucchini A, Ricci D. Antioxidant activity of citrus paradisi seeds glyceric extract. Fitoterapia 2004;75:221-224.   DOI
10 Koczulla R, von Degenfeld G, Kupatt C, Krotz F, Zahler S, Gloe T, et al. An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest 2003;111:1665-1672.   DOI
11 Two AM, Wu W, Gallo RL, Hata TR. Rosacea: part I. Introduction, categorization, histology, pathogenesis, and risk factors. J Am Acad Dermatol 2015;72:749-758.   DOI
12 Earley S. Vanilloid and melastatin transient receptor potential channels in vascular smooth muscle. Microcirculation 2010;17:237-249.   DOI
13 Morizane S, Yamasaki K, Muhleisen B, Kotol PF, Murakami M, Aoyama Y, et al. Cathelicidin antimicrobial peptide LL-37 in psoriasis enables keratinocyte reactivity against TLR9 ligands. J Invest Dermatol 2012;132:135-143.   DOI
14 Wang TT, Nestel FP, Bourdeau V, Nagai Y, Wang Q, Liao J, et al. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol 2004;173:2909-2912.   DOI
15 Nilius B, Owsianik G, Voets T, Peters JA. Transient receptor potential cation channels in disease. Physiol Rev 2007;87:165-217.   DOI
16 Steinhoff M, Schauber J, Leyden JJ. New insights into rosacea pathophysiology: a review of recent findings. J Am Acad Dermatol 2013;69:S15-S26.   DOI
17 Yamasaki K, Di Nardo A, Bardan A, Murakami M, Ohtake T, Coda A, et al. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med 2007;13:975-980.   DOI
18 Yamasaki K, Schauber J, Coda A, Lin H, Dorschner RA, Schechter NM, et al. Kallikrein-mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin. FASEB J 2006;20:2068-2080.   DOI
19 Schauber J, Gallo RL. The vitamin D pathway: a new target for control of the skin's immune response? Exp Dermatol 2008;17:633-639.   DOI
20 Pecze L, Szabo K, Szell M, Josvay K, Kaszas K, Kusz E, et al. Human keratinocytes are vanilloid resistant. PLoS One 2008;3:e3419.   DOI
21 Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 1997;389:816-824.   DOI
22 Sulk M, Seeliger S, Aubert J, Schwab VD, Cevikbas F, Rivier M, et al. Distribution and expression of non-neuronal transient receptor potential (TRPV) ion channels in rosacea. J Invest Dermatol 2012;132:1253-1262.   DOI
23 Schauber J, Dorschner RA, Coda AB, Buchau AS, Liu PT, Kiken D, et al. Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism. J Clin Invest 2007;117:803-811.   DOI
24 Huggenberger R, Detmar M. The cutaneous vascular system in chronic skin inflammation. J Investig Dermatol Symp Proc 2011;15:24-32.   DOI
25 Gomaa AH, Yaar M, Eyada MM, Bhawan J. Lymphangiogenesis and angiogenesis in non-phymatous rosacea. J Cutan Pathol 2007;34:748-753.   DOI
26 Balato A, Lembo S, Mattii M, Schiattarella M, Marino R, De Paulis A, et al. IL-33 is secreted by psoriatic keratinocytes and induces pro-inflammatory cytokines via keratinocyte and mast cell activation. Exp Dermatol 2012;21:892-894.   DOI
27 Borelli C, Becker B, Thude S, Fehrenbacher B, Isermann D. Dermasence refining gel modulates pathogenetic factors of rosacea in vitro. J Cosmet Dermatol 2017;16:e31-e36.   DOI
28 Denizot F, Lang R. Rapid colorimetric assay for cell growth and survival: modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods 1986;89:271-277.   DOI
29 Thibaut de Menonville ST, Rosignoli C, Soares E, Roquet M, Bertino B, Chappuis JP, et al. Topical treatment of rosacea with ivermectin inhibits gene expression of cathelicidin innate immune mediators, LL-37 and KLK5, in reconstructed and ex vivo skin models. Dermatol Ther (Heidelb) 2017;7:213-225.   DOI
30 Lee JB, Bae SH, Moon KR, Na EY, Yun SJ, Lee SC. Light-emitting diodes downregulate cathelicidin, kallikrein and toll-like receptor 2 expressions in keratinocytes and rosacea-like mouse skin. Exp Dermatol 2016;25:956-961.   DOI
31 Woo DH. Stabilization to sunlight of natural coloring matter by soluble methyl-hesperidin. Korean J Food Sci Technol 2000;32:50-55.
32 Morizane S, Yamasaki K, Kabigting FD, Gallo RL. Kallikrein expression and cathelicidin processing are independently controlled in keratinocytes by calcium, vitamin D(3), and retinoic acid. J Invest Dermatol 2010;130:1297-1306.   DOI
33 Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D. Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet 1993;342:1007-1011.   DOI
34 Vinson JA, Su X, Zubik L, Bose P. Phenol antioxidant quantity and quality in foods: fruits. J Acric Food Chem 2001;49:5315-5321.   DOI
35 Lee SL, Seo CS, Kim JH, Shin HK. Contents of poncirin and naringin in fruit of poncirus trifoliata according to different harvesting times and locations for two years. Korean J Pharmacogn 2011;42:138-143.
36 Yang HS, Eun JB. Fermentation and sensory characteristics of Korean traditional fermented liquor (makgeolli) added with citron (Citrus junos SIEB ex TANAKA) juice. Korean J Food Sci Technol 2011;43:438-445.   DOI
37 Kim SY, Shin KS. Evaluation of physiological activities of the citron (Citrus junos Sieb. ex TANAKA) seed extracts. Prev Nutr Food Sci 2013;18:196-202.   DOI
38 Woo KL, Kim JI, Kim MC, Chang DK. Determination of flavonoid and limonoid compounds in citron (Citrus junos Sieb. et Tanaka) seeds by HPLC and HPLC/MS. J Korean Soc Food Sci Nutr 2006;35:353-358.   DOI
39 Manners GD. Citrus limonoids: analysis, bioactivity, and biomedical prospects. J Agric Food Chem 2007;55:8285-8294.   DOI
40 Miller EG, Gonzales-Sanders AP, Couvillon AM, Wright JM, Hasegawa S, Lam LK. Inhibition of hamster buccal pouch carcinogenesis by limonin 17-beta-D-glucopyranoside. Nutr Cancer 1992;17:1-7.   DOI
41 El-Readi MZ, Hamdan D, Farrag N, El-Shazly A, Wink M. Inhibition of P-glycoprotein activity by limonin and other secondary metabolites from citrus species in human colon and leukaemia cell lines. Eur J Pharmacol 2010;626:139-145.   DOI