Topical Application of Cudrania tricuspidata Stem Extract Inhibits Atopic Dermatitis-Like Skin Lesions in an NC/Nga Mouse Model: An Experimental Animal Study — Oak Academic Publishing
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Topical Application of Cudrania tricuspidata Stem Extract Inhibits Atopic Dermatitis-Like Skin Lesions in an NC/Nga Mouse Model: An Experimental Animal Study
Division of Molecular Therapeutics Development, Hanyang Biomedical Research Institute, Hanyang University, Seoul, Republic of Korea
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Department of Clinical Nutrition, Shintong Rehabilitation Clinic, Yongin, Republic of Korea
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Department of Food & Nutrition, Hanyang Women’s University, Seoul, Republic of Korea
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Department of Pharmacology, College of Medicine, Hanyang University, Seoul, Republic of Korea
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Institute of Medical Science, Hanyang University, Seoul, Republic of Korea
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Department of Pharmacology, College of Medicine, Hanyang University, Seoul, Republic of Korea
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Department of New Drug Development, College of Medicine, Hanyang University, Seoul, Republic of Korea
,
Department of Pharmacology, College of Medicine, Hanyang University, Seoul, Republic of Korea
,
Department of Biology, Johns Hopkins University, Maryland, USA
,
Division of Molecular Therapeutics Development, Hanyang Biomedical Research Institute, Hanyang University, Seoul, Republic of Korea
,
Department of Pharmacology, College of Medicine, Hanyang University, Seoul, Republic of Korea
,
Institute of Medical Science, Hanyang University, Seoul, Republic of Korea
,
Department of New Drug Development, College of Medicine, Hanyang University, Seoul, Republic of Korea
,
Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Republic of Korea
1 Division of Molecular Therapeutics Development, Hanyang Biomedical Research Institute, Hanyang University, Seoul, Republic of Korea
2 Department of Clinical Nutrition, Shintong Rehabilitation Clinic, Yongin, Republic of Korea
3 Department of Food & Nutrition, Hanyang Women’s University, Seoul, Republic of Korea
4 Department of Pharmacology, College of Medicine, Hanyang University, Seoul, Republic of Korea
5 Institute of Medical Science, Hanyang University, Seoul, Republic of Korea
6 Department of Pharmacology, College of Medicine, Hanyang University, Seoul, Republic of Korea
7 Department of New Drug Development, College of Medicine, Hanyang University, Seoul, Republic of Korea
8 Department of Pharmacology, College of Medicine, Hanyang University, Seoul, Republic of Korea
9 Department of Biology, Johns Hopkins University, Maryland, USA
10 Division of Molecular Therapeutics Development, Hanyang Biomedical Research Institute, Hanyang University, Seoul, Republic of Korea
11 Department of Pharmacology, College of Medicine, Hanyang University, Seoul, Republic of Korea
12 Institute of Medical Science, Hanyang University, Seoul, Republic of Korea
13 Department of New Drug Development, College of Medicine, Hanyang University, Seoul, Republic of Korea
14 Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Republic of Korea
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by elevated immunoglobulin E (IgE), mast cell infiltration and skin lesions including pruritus, erythema and eczema. Cudrania tricuspidata extracts have been clinically administered for a long time in the East Asia including Korean and China as a home-remedy to diminish the inflammation of gastritis and hepatitis. To examine whether it works on AD or not, an AD-like animal model was experimented in this study. AD was induced by applying Dermatophagoides farinae ( D. farinae ) extract to the backs of 9-week old NC/Nga mice for 21 days. Following this, an ethanol extract of C. tricuspidata stems (EECT) was applied topically for 14 days to the sensitized skin, while distilled water was used as a control (EECT0 mice). Anti-AD effects of EECT were evaluated using scores for AD-like skin lesions, serum IgE levels and mast cell counts in the skin dermal layers to assess inflammation. Topically applied ethanol extract of Cudrania tricuspidata stems (EECT 7.5, 25 and 75 mg/mL) markedly reduced AD-like skin lesions after 4 days (by 30.1%, 31.4% and 38.5%, respectively) and also after 14 days (by 63.6%, 66.1% and 49.6%, respectively), while distilled water improved AD by 17.8% and 38.7%, respectively (p < 0.05). Serum IgE production was reduced in the EECT7.5, EECT25 and EECT75 groups after 4 days (by 57.6%, 65.9% and 59.3%, respectively) and after 14 days of the treatment (by 82.0%, 79.6% and 75.3%, respectively), while distilled water decreased it by 38.8% and 62.3% (p = 0.0001 and p = 0.0001, respectively). Mast cell counts increased after sensitization by D. farinae extract (p = 0.003) and EECT attenuated the mast cell overproduction, and reduced mast cell degranulation markedly. Attenuation was most obvious in the early stage of EECT treatment when the AD was most acute.
KeywordsAtopic Dermatitis<i>Cudrania tricuspidata StemDermatophagoides farina</i>Immunoglobulin E (IgE)NC/Nga Mouse
Leung, D.Y.M. (1999) Pathogenesis of Atopic Dermatitis. Journal of Allergy and Clinical Immunology, 104, S99-S108. http://dx.doi.org/10.1016/S0091-6749(99)70051-5
Joo, S.S., Kim, S.G., Choi, S.E., Kim, Y.-B., Park, H.Y., Seo, S.J., Choi, Y.W., Lee, M.W. and Lee, D.I. (2009) Suppression of T Cell Activation by Hirsutenone, Isolated from the Bark of Alnus japonica, and Its Therapeutic Advantages for Atopic Dermatitis. European Journal of Pharmacology, 614, 98-105. http://dx.doi.org/10.1016/j.ejphar.2009.04.047
Damsgaard, T.E., Olesen, A.B., SØrensen, F.B., Thestrup-Pedersen, K. and SchiØtz, P.O. (1997) Mast Cells and Atopic Dermatitis. Stereological Quantification of Mast Cells in Atopic Dermatitis and Normal Human Skin. Archives of Dermatological Research, 289, 256-260. http://dx.doi.org/10.1007/s004030050189
Cho, E.J., Yokozawa, T., Rhyu, D.Y., Kim, S.C., Shibahara, N. and Park, J.C. (2003) Study on the Inhibitory Effects of Korean Medicinal Plants and Their Main Compounds on the 1,1-Diphenyl-2-Picrylhydrazyl Radical. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology, 10, 544-551. http://dx.doi.org/10.1078/094471103322331520
Song, M.J. and Kim, H. (2011) Ethnomedicinal Application of Plants in the Western Plain Region of North Jeolla Province in Korea. Journal of Ethnopharmacology, 137, 167-175. http://dx.doi.org/10.1016/j.jep.2011.05.001
Shi, L., Fu, Y.L. and Chen, K.S. (2007) A Novel Water-Soluble α-(1→4)-Glucan from the Root of Cudrania tricuspidata. Fitoterapia, 78, 298-301. http://dx.doi.org/10.1016/j.fitote.2007.03.007
Kang, B., Liu, S., Cai, D. and Wen, Y. (2006) Species Composition and Correlation of Understory Woody Plants in Chinese Fir Plantation in the Lower Subtropical Area. Frontiers of Biology in China, 1, 423-429. http://dx.doi.org/10.1007/s11515-006-0057-0
Tian, Y.H., Kim, H.C., Cui, J.M. and Kim, Y.C. (2005) Hepatoprotective Constituents of Cudrania tricuspidata. Archives of Pharmacal Research, 28, 44-48. http://dx.doi.org/10.1007/BF02975134
An, R.B., Sohn, D.H. and Kim, Y.C. (2006) Hepatoprotective Compounds of the Roots of Cudrania tricuspidata on Tacrine-Induced Cytotoxicity in Hep G2 Cells. Biological &Pharmaceutical Bulletin, 29, 838-840. http://dx.doi.org/10.1248/bpb.29.838
Kim, O.K., Ho, J.N., Nam, D.E., Jun, W., Hwang, K.T., Kang, J.E., Chae, O.S. and Lee, J. (2012) Hepatoprotective Effect of Curdrania tricuspidata Extracts against Oxidative Damage. Journal of the Korean Society of Food Science and Nutrition, 41, 7-13. http://dx.doi.org/10.3746/jkfn.2012.41.1.007
Kang, D.G., Hur, T.Y., Lee, G.M., Oh, H., Kwon, T.O., Sohn, E.J. and Lee, H.S. (2002) Effects of Cudrania tricuspidata Water Extract on Blood Pressure and Renal Functions in NO-Dependent Hypertension. Life Sciences, 70, 2599- 2609. http://dx.doi.org/10.1016/S0024-3205(02)01547-3
Park, J.H., Lee, K.W., Sung, K.S., Kim, S.S., Cho, K.D., Lee, B.H. and Han, C.K. (2012) Effect of Diets with Mulberry Leaf and Cudrania tricuspidata Leaf Powder Supplements on Blood Glucose-Related Biomarkers in Streptozotocin-Induced Diabetic Rats. Journal of the Korean Society of Food Science and Nutrition, 41, 766-773. http://dx.doi.org/10.3746/jkfn.2012.41.6.766
Park, W.Y., Ro, J.S. and Lee, K.S. (2001) Hypoglycemic Effect of Cudrania tricuspidata Root Bark. Korean Journal of Pharmacognosy, 32, 248-252.
Oh, P.S., Lee, H.J. and Lim, K.T. (2009) Inhibitory Effect of Glycoprotein Isolated from Cudrania tricuspidata Bureau on Histamine Release and COX-2 Activity in RBL-2H3 Cells. Korean Journal of Food Science and Technology, 41, 405-412.
Park, B.H., Back, K.Y., Lee, S.I. and Kim, S.D. (2008) Quality and Antioxidative Characteristics of Cudrania tricuspidata Leaves Tea. Korean Journal of Food Preservation, 15, 461-468.
Jeong, C.H., Choi, G.N., Kim, J.H., Kwak, J.H., Heo, H.J., Shim, K.H., Cho, B.R., Bae, Y.I. and Choi, J.S. (2009) In Vitro Antioxidative Activities and Phenolic Composition of Hot Water Extract from Different Parts of Cudrania tricuspidata. Preventive Nutrition and Food Science, 14, 283-289. http://dx.doi.org/10.3746/jfn.2009.14.4.283
Han, X.H., Hong, S.S., Jin, Q., Li, D., Kim, H.-K., Lee, J., Kwon, S.H., Lee, D., Lee, C.-K., Lee, M.K. and Hwang, B.Y. (2009) Prenylated and Benzylated Flavonoids from the Fruits of Cudrania tricuspidata. Journal of Natural Products, 72, 164-167. http://dx.doi.org/10.1021/np800418j
Kim, Y.C., Hur, J., Sohn, D.H. and Kim, H.S. (2008) Antibacterial Compounds of the Root Barks of Cudrania tricuspidata. Korean Journal of Pharmacognosy, 39, 246-248.
Kim, S.H., Kim, N.J., Choi, J.S. and Park, J.C. (1993) Determination of Flavonoid by HPLC and Biological Activities from the Leaves of Cudrania tricuspidata Bureau. Journal of the Korean Society of Food Science and Nutrition, 22, 68-72.
Park, J.C., Young, H.S. and Choi, J.S. (1992) Constituents of Cudrania tricuspidata in Korea. Yakhak Hoeji, 36, 40-45.
Lee, H., Ha, H., Lee, J.K., Seo, C.S., Lee, N.H., Jung, D.Y., Park, S.J. and Shin, H.K. (2012) The Fruits of Cudrania tricuspidata Suppress Development of Atopic Dermatitis in NC/Nga Mice. Phytotherapy Research, 26, 594-599. http://dx.doi.org/10.1002/ptr.3577
Yamamoto, M., Haruna, T., Yasui, K., Takahashi, H., Iduhara, M., Takaki, S., Deguchi, M. and Arimura, A. (2007) A Novel Atopic Dermatitis Model Induced by Topical Application with Dermatophagoides farinae Extract in NC/Nga Mice. Allergology International, 56, 139-148. http://dx.doi.org/10.2332/allergolint.O-06-458
Leung, D.Y., Hirsch, R.L., Schneider, L., Moody, C., Takaoka, R., Li, S.H., Meyerson, L.A., Mariam, S.G., Goldstein, G. and Hanifin, J.M. (1990) Thymopentin Therapy Reduces the Clinical Severity of Atopic Dermatitis. The Journal of Allergy and Clinical Immunology, 85, 927-933. http://dx.doi.org/10.1016/0091-6749(90)90079-J
Yamaguchi, T., Maekawa, T., Nishikawa, Y., Nojima, H., Kaneko, M., Kawakita, T., Miyamoto, T. and Kuraishi, Y. (2001) Characterization of Itch-Associated Responses of NC Mice with Mite-Induced Chronic Dermatitis. Journal of Dermatological Science, 25, 20-28. http://dx.doi.org/10.1016/S0923-1811(00)00099-2
Administration KFD (2010) The Guideline for Effect Tests of Herbal Medicines: Atopic Dermatitis. In: Department of Bio-Herbal Medicine KFDA, Ed., Korean Food and Drug Administration, Seoul, 1-14.
Damsgaard, T.E., Olesen, A.B., SØrensen, F.B., Thestrup-Pedersen, K. and SchiØtz, P.O. (1997) Mast Cells and Atopic Dermatitis. Stereological Quantification of Mast Cells in Atopic Dermatitis and Normal Human Skin. Archives of Dermatological Research, 289, 256-260. http://dx.doi.org/10.1007/s004030050189
Internet Pathology Laboratory (2011) Mast Cells—O TOLUIDINE Blue. http://www-medlib.med.utah.edu/WebPath/webpath.html
Leung, D.Y.M. (2006) New Insights into the Complex Gene-Environment Interactions Evolving into Atopic Dermatitis. The Journal of Allergy and Clinical Immunology, 118, 37-39. http://dx.doi.org/10.1016/j.jaci.2006.04.045
Kawakami, T., Ando, T., Kimura, M., Wilson, B.S. and Kawakami, Y. (2009) Mast Cells in Atopic Dermatitis. Current Opinion in Immunology, 21, 666-678. http://dx.doi.org/10.1016/j.coi.2009.09.006
Matsuda, H., Watanabe, N., Geba, G.P., Sperl, J., Tsudzuki, M., Hiroi, J., Matsumoto, M., Ushio, H., Saito, S., Askenase, P.W. and Ra, C. (1997) Development of Atopic Dermatitis-Like Skin Lesion with IgE Hyperproduction in NC/ Nga Mice. International Immunology, 9, 461-466. http://dx.doi.org/10.1093/intimm/9.3.461
Park, S., Lee, J.B. and Kang, S. (2012) Topical Application of Chrysanthemum indicum L. Attenuates the Development of Atopic Dermatitis-Like Skin Lesions by Suppressing Serum IgE Levels, IFN-gamma, and IL-4 in Nc/Nga Mice. Evidence-Based Complementary and Alternative Medicine, 2012, Article ID: 821967. http://dx.doi.org/10.1155/2012/821967
Van Bever, H.P. (1992) Recent Advances in the Pathogenesis of Atopic Dermatitis. European Journal of Pediatrics, 151, 870-873. http://dx.doi.org/10.1007/BF01954120
Cikler, E., Ersoy, Y., Cetinel, S. and Ercan, F. (2009) The Leukotriene d4 Receptor Antagonist, Montelukast, Inhibits Mast Cell Degranulation in the Dermis Induced by Water Avoidance Stress. Acta Histochemica, 111, 112-118. http://dx.doi.org/10.1016/j.acthis.2008.04.006
Seo, Y.M. and Jeong, S.H. (2015) Effects of Blending Oil of Lavender and Thyme on Oxidative Stress, Immunity, and Skin Condition in Atopic Dermatitis Induced Mice. Journal of Korean Academy of Nursing, 45, 367-377. http://dx.doi.org/10.4040/jkan.2015.45.3.367
Cikler, E., Ercan, F., Cetinel, S., Contuk, G. and Sener, G. (2009) The Protective Effects of Melatonin against Water Avoidance Stress-Induced Mast Cell Degranulation in Dermis. Acta Histochemica, 106, 467-475. http://dx.doi.org/10.1016/j.acthis.2004.10.001
Elias, P.M. and Schmuth, M. (2009) Abnormal Skin Barrier in the Etiopathogenesis of Atopic Dermatitis. Current Opinion in Allergy & Clinical Immunology, 9, 437-446. http://dx.doi.org/10.1097/ACI.0b013e32832e7d36
Yamashita, H., Tasaki, D., Makino, T., Matsuoka, K., Nose, M., Inagaki, N. and Mizukami, H. (2009) The Role of IgE and Repeated Challenge in the Induction of Persistent Increases in Scratching Behavior in a Mouse Model of Allergic Dermatitis. European Journal of Pharmacology, 605, 153-157. http://dx.doi.org/10.1016/j.ejphar.2009.01.006
Cowden, J.M., Zhang, M., Dunford, P.J. and Thurmond, R.L. (2010) The Histamine H4 Receptor Mediates Inflammation and Pruritus in Th2-Dependent Dermal Inflammation. Journal of Investigative Dermatology, 130, 1023-1033. http://dx.doi.org/10.1038/jid.2009.358