Sika deer (Cervus nippon) velvet antler ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis-like clinical signs in a rodent model
Young-Jin Choi A , Meiqi Fan A , Yonghai Yu B , Xiaoli Wang B , Yujiao Tang A B C and Eun-Kyung Kim A CA Division of Food Bioscience, College of Biomedical and Health Sciences, Konkuk University, 268 Chungwondaero, Chungju 27478, Republic of Korea.
B School of Bio-science and Food Engineering, Changchun University of Science and Technology, 7089 Weixing Road, Changchun 130-600, China.
C Corresponding author. Email: yuanxi00@126.com; eunkyungkim@kku.ac.kr
Animal Production Science 60(10) 1357-1363 https://doi.org/10.1071/AN19500
Submitted: 12 September 2019 Accepted: 18 January 2020 Published: 13 May 2020
Abstract
Context: Deer velvet is a rarely used component in traditional Chinese medicine and has beneficial effects against several diseases. As a substance that covers the bone and cartilage of immature antlers, deer velvet is a natural cytokine ‘storeroom’ that is rich in protein and proteoglycans. Recently, proteoglycans have been shown to have beneficial effects against inflammation.
Aims: To determine whether antler extract possesses therapeutic effects in a mouse model of atopic dermatitis (AD) and to explore the underlying mechanisms of action.
Methods: BALB/c mice were randomly divided into the following groups: control, AD, and AD + antler groups. We established an in vivo AD model by repeatedly exposing the ears of mice to Dermatophagoides farinae extract (house dust-mite extract) and 2,4-dinitrochlorobenzene once per week for 4 weeks. On the day after induction, ear thickness was measured. Antler extract (100 mg/kg) was administered orally once a day for 26 days. After 4 weeks of treatment with antler extract, the epidermal and dermal ear thickness, mast-cell infiltration, spleen weight, and lymph-node weight were measured. In addition, the mRNA levels of several pathogenic cytokines in the ears were measured. The concentrations of IL-4, IL-5, IL-10, IL-31 and IL-17 mRNA in the skin lesions of each group were measured by quantitative polymerase chain reaction.
Key results: Epidermal and dermal ear thickness, mast-cell infiltration, lymph-node weight, and gene expression levels of pathogenic cytokines in ear tissue were diminished following oral administration of antler extract, unlike in the control group.
Conclusions: The results of the present study strongly suggest that antler extract exhibits therapeutic activity against atopic dermatitis via regulation of inflammatory response.
Implications: Further exploration of the mechanisms of action of antler extract will be important for clinical application.
Additional keywords: allergic disease, inflammation. skin disease.
References
Bai XY, Liu P, Chai YW, Wang Y, Ren SH, Li YY, Zhou H (2020) Artesunate attenuates 2, 4-dinitrochlorobenzene-induced atopic dermatitis by down-regulating Th17 cell responses in BALB/c mice. European Journal of Pharmacology 874, 173020| Artesunate attenuates 2, 4-dinitrochlorobenzene-induced atopic dermatitis by down-regulating Th17 cell responses in BALB/c mice.Crossref | GoogleScholarGoogle Scholar | 32087254PubMed |
Banerjee S, Resch Y, Chen KW, Swoboda I, Focke-Tejkl M, Blatt K, Novak N, Wickman M, Hage M, Ferrara R, Mari A (2015) Der p 11 is a major allergen for house dust mite-allergic patients suffering from atopic dermatitis. The Journal of Investigative Dermatology 135, 102–109.
| Der p 11 is a major allergen for house dust mite-allergic patients suffering from atopic dermatitis.Crossref | GoogleScholarGoogle Scholar | 24999597PubMed |
Boguniewicz M, Leung DY (2011) Atopic dermatitis: a disease of altered skin barrier and immune dysregulation. Immunological Reviews 242, 233–246.
| Atopic dermatitis: a disease of altered skin barrier and immune dysregulation.Crossref | GoogleScholarGoogle Scholar | 21682749PubMed |
Borish L, Joseph BZ (1992) Inflammation and the allergic response. The Medical Clinics of North America 76, 765–787.
| Inflammation and the allergic response.Crossref | GoogleScholarGoogle Scholar | 1614234PubMed |
Cavani A, Pennino D, Eyerich K (2012) Th17 and Th22 in skin allergy. New Trends in Allergy and Atopic Eczema 96, 39–44.
| Th17 and Th22 in skin allergy.Crossref | GoogleScholarGoogle Scholar |
Chalmers J, Deckert S, Schmitt J (2015) Reaching clinically relevant outcome measures for new pharmacotherapy and immunotherapy of atopic eczema. Current Opinion in Allergy and Clinical Immunology 15, 227–233.
Chan LS, Robinson N, Xu L (2001) Expression of interleukin-4 in the epidermis of transgenic mice results in a pruritic inflammatory skin disease: an experimental animal model to study atopic dermatitis. The Journal of Investigative Dermatology 117, 977–983.
| Expression of interleukin-4 in the epidermis of transgenic mice results in a pruritic inflammatory skin disease: an experimental animal model to study atopic dermatitis.Crossref | GoogleScholarGoogle Scholar | 11676841PubMed |
Choi EJ, Park ZY, Kim EK (2016) Chemical composition and inhibitory effect of Lentinula edodes ethanolic extract on experimentally induced atopic dermatitis in vitro and in vivo. Molecules 21, 993.
Deleuran M, Vestergaard C (2014) Clinical heterogeneity and differential diagnosis of atopic dermatitis. British Journal of Dermatology 170, 2–6.
| Clinical heterogeneity and differential diagnosis of atopic dermatitis.Crossref | GoogleScholarGoogle Scholar | 24720512PubMed |
Fukuyama A, Tanaka K, Kakizaki I, Kasai K, Chiba M, Nakamura T, Mizunuma H (2012) Anti-inflammatory effect of proteoglycan and progesterone on human uterine cervical fibroblasts. Life Sciences 90, 484–488.
| Anti-inflammatory effect of proteoglycan and progesterone on human uterine cervical fibroblasts.Crossref | GoogleScholarGoogle Scholar | 22314502PubMed |
Hong SH, Ku JM, Kim HI, Lee SJ, Lim YS, Seo HS, Shin YC, Ko SG (2018) Oral administration of Cervus nippon mantchuricus extract suppresses 2,4-dinitrochlorobenzene-induced atopic dermatitis in BALB/c mice and inflammatory effects in mast cells. International Journal of Molecular Medicine 42, 2961–2971.
Koga C, Kabashima K, Shiraishi N, Kobayashi M, Tokura Y (2008) Possible pathogenic role of Th17 cells for atopic dermatitis. The Journal of Investigative Dermatology 128, 2625–2630.
| Possible pathogenic role of Th17 cells for atopic dermatitis.Crossref | GoogleScholarGoogle Scholar | 18432274PubMed |
Kolls JK (2010) Th17 cells in mucosal immunity and tissue inflammation. Seminars in Immunopathology 32, 1–2.
| Th17 cells in mucosal immunity and tissue inflammation.Crossref | GoogleScholarGoogle Scholar | 20182729PubMed |
Kuo CY, Wang T, Dai TY, Wang CH, Chen KN, Chen YP, Chen MJ (2012) Effect of the velvet antler of Formosan sambar deer (Cervus unicolor swinhoei) on the prevention of an allergic airway response in mice. Evidence-Based Complementary and Alternative Medicine 2012, 481318
| Effect of the velvet antler of Formosan sambar deer (Cervus unicolor swinhoei) on the prevention of an allergic airway response in mice.Crossref | GoogleScholarGoogle Scholar | 23346203PubMed |
Lee SH, Yang HW, Ding Y, Wang Y, Jeon YJ, Moon SH, Jeon BT, Sung SH (2015) Anti-inflammatory effects of enzymatic hydrolysates of velvet antler in raw 264.7 cells in vitro and zebrafish model. EXCLI Journal 14, 1122–1132.
Lyons JJ, Milner JD, Stone KD (2015) Atopic dermatitis in children: clinical features, pathophysiology, and treatment. Immunology and Allergy Clinics 35, 161–183.
| Atopic dermatitis in children: clinical features, pathophysiology, and treatment.Crossref | GoogleScholarGoogle Scholar |
Ma L, Xue HB, Wang F, Shu CM, Zhang JH (2015) MicroRNA‐155 may be involved in the pathogenesis of atopic dermatitis by modulating the differentiation and function of T helper type 17 (Th17) cells. Clinical and Experimental Immunology 181, 142–149.
| MicroRNA‐155 may be involved in the pathogenesis of atopic dermatitis by modulating the differentiation and function of T helper type 17 (Th17) cells.Crossref | GoogleScholarGoogle Scholar | 25761610PubMed |
Miossec P, Kolls JK (2012) Targeting IL-17 and TH17 cells in chronic inflammation. Nature Reviews. Drug Discovery 11, 763–776.
| Targeting IL-17 and TH17 cells in chronic inflammation.Crossref | GoogleScholarGoogle Scholar | 23023676PubMed |
Morren MA, Przybilla B, Bamelis M, Heykants B, Reynaers A, Degreef H (1994) Atopic dermatitis: triggering factors. Journal of the American Academy of Dermatology 31, 467–473.
| Atopic dermatitis: triggering factors.Crossref | GoogleScholarGoogle Scholar | 8077475PubMed |
Neis MM, Peters B, Dreuw A, Wenzel J, Bieber T, Mauch C, Krieg T, Stanzel T, Heinrich PC, Merk HF, Bosio A, Baron JM, Hermanns HM (2006) Enhanced expression levels of IL-31 correlate with IL-4 and IL-13 in atopic and allergic contact dermatitis. The Journal of Allergy and Clinical Immunology 118, 930–937.
| Enhanced expression levels of IL-31 correlate with IL-4 and IL-13 in atopic and allergic contact dermatitis.Crossref | GoogleScholarGoogle Scholar | 17030248PubMed |
Nobbe S, Dziunycz P, Mühleisen B, Bilsborough J, Dillon SR, French LE, Hofbauer GF (2012) IL-31 expression by inflammatory cells is preferentially elevated in atopic dermatitis. Acta Dermato-Venereologica 92, 24–28.
| IL-31 expression by inflammatory cells is preferentially elevated in atopic dermatitis.Crossref | GoogleScholarGoogle Scholar | 22041865PubMed |
Pravin SK, Durgacharan AB, Dinesh MS (2010) Deer antlers: traditional use and future perspectives. Indian Journal of Traditional Knowledge 9, 245–251.
Qiu FP, Ma B, Wang ZB, Xie SL (2007) Study on the purification and activity of antler plate protein. Journal of Changchun University of Technology 28, 144–147.
Raap U, Wichmann K, Bruder M, Ständer S, Wedi B, Kapp A, Werfel T (2008) Correlation of IL-31 serum levels with severity of atopic dermatitis. The Journal of Allergy and Clinical Immunology 122, 421–423.
| Correlation of IL-31 serum levels with severity of atopic dermatitis.Crossref | GoogleScholarGoogle Scholar | 18678344PubMed |
Saito S, Nakashima A, Shima T, Ito M (2010) Th1/Th2/Th17 and regulatory T‐cell paradigm in pregnancy. American Journal of Reproductive Immunology 63, 601–610.
| Th1/Th2/Th17 and regulatory T‐cell paradigm in pregnancy.Crossref | GoogleScholarGoogle Scholar | 20455873PubMed |
Saraiva M, O’Garra A (2010) The regulation of IL-10 production by immune cells. Nature Reviews. Immunology 10, 170-181
| The regulation of IL-10 production by immune cells.Crossref | GoogleScholarGoogle Scholar | 20154735PubMed |
Siegel R, Ward E, Brawley O, Jemal A (2011) Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA: A Cancer Journal for Clinicians 61, 212–236.
| Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths.Crossref | GoogleScholarGoogle Scholar |
Sugaya M (2020) The role of Th17-related cytokines in atopic dermatitis. International Journal of Molecular Sciences 21, 1314
| The role of Th17-related cytokines in atopic dermatitis.Crossref | GoogleScholarGoogle Scholar |
Suárez-Fariñas M, Dhingra N, Gittler J, Shemer A, Cardinale I, de Guzman Strong C, Krueger JG, Guttman-Yassky E (2013) Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis. The Journal of Allergy and Clinical Immunology 132, 361–370.
| Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis.Crossref | GoogleScholarGoogle Scholar | 23777851PubMed |
Sunwoo HH, Sim JS (2000) Potential uses of velvet antler as nutraceuticals, functional and medical foods in the West. Journal of Nutraceuticals, Functional & Medical Foods 2, 5–23.
| Potential uses of velvet antler as nutraceuticals, functional and medical foods in the West.Crossref | GoogleScholarGoogle Scholar |
Tang Y, Jeon BT, Wang Y, Choi EJ, Park PJ, Seong HJ, Moon SH, Kim EK (2015) First evaluation of the biologically active substances and antioxidant potential of regrowth velvet antler by means of multiple biochemical assays. Journal of Chemistry 2015, 975292
Tangye SG, Pillay B, Randall KL, Avery DT, Phan TG, Gray P, Ziegler JB, Smart JM, Peake J, Arkwright PD, Hambleton S, Orange J, Goodnow CC, Uzel G, Casanova JL, Reyes SO, Freeman AL, Su HC, Ma CS (2017) Dedicator of cytokinesis 8–deficient CD4+ T cells are biased to a TH2 effector fate at the expense of TH1 and TH17 cells. The Journal of Allergy and Clinical Immunology 139, 933–949.
| Dedicator of cytokinesis 8–deficient CD4+ T cells are biased to a TH2 effector fate at the expense of TH1 and TH17 cells.Crossref | GoogleScholarGoogle Scholar | 27554822PubMed |
Weaver CT, Harrington LE, Mangan PR, Gavrieli M, Murphy KM (2006) Th17: an effector CD4 T cell lineage with regulatory T cell ties. Immunity 24, 677–688.
| Th17: an effector CD4 T cell lineage with regulatory T cell ties.Crossref | GoogleScholarGoogle Scholar | 16782025PubMed |
Wedi B, Raap U, Lewrick H, Kapp A (1997) Delayed eosinophil programmed cell death in vitro: a common feature of inhalant allergy and extrinsic and intrinsic atopic dermatitis. The Journal of Allergy and Clinical Immunology 100, 536–543.
| Delayed eosinophil programmed cell death in vitro: a common feature of inhalant allergy and extrinsic and intrinsic atopic dermatitis.Crossref | GoogleScholarGoogle Scholar | 9338549PubMed |
Weidinger S, Beck LA, Bieber T, Kabashima K, Irvine AD (2016) Atopic dermatitis. Lancet 387, 1109–1122.
| Atopic dermatitis.Crossref | GoogleScholarGoogle Scholar | 26377142PubMed |
Wu F, Li H, Jin L, Li X, Ma Y, You J, Xu Y (2013) Deer antler base as a traditional Chinese medicine: a review of its traditional uses, chemistry and pharmacology. Journal of Ethnopharmacology 145, 403–415.
| Deer antler base as a traditional Chinese medicine: a review of its traditional uses, chemistry and pharmacology.Crossref | GoogleScholarGoogle Scholar | 23246455PubMed |
Zha E, Dandan L, Bai X, Zhou T, Li Y, Shenyang G, Yue X (2016) A recombinant polypeptide from velvet antler of Cervus nippon Temminck exhibits similar immunomodulatory effects as its natural counterpart. Immunopharmacology and Immunotoxicology 38, 385–389.
| A recombinant polypeptide from velvet antler of Cervus nippon Temminck exhibits similar immunomodulatory effects as its natural counterpart.Crossref | GoogleScholarGoogle Scholar | 27600490PubMed |
Zhang ZQ, Wang Y, Zhang H, Zhang W, Zhang Y, Wang BX (1994) Anti-inflammatory effects of pilose antler peptide. Acta Pharmacologica Sinica 15, 282–284.
Zhang Q, Putheti P, Zhou Q, Liu Q, Gao W (2008) Structures and biological functions of IL-31 and IL-31 receptors. Cytokine & Growth Factor Reviews 19, 347–356.
| Structures and biological functions of IL-31 and IL-31 receptors.Crossref | GoogleScholarGoogle Scholar |