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Published in: BMC Complementary Medicine and Therapies 1/2015

Open Access 01-12-2015 | Research article

Effects of Ixeris dentata water extract and caffeic acid on allergic inflammation in vivo and in vitro

Authors: Yong-Deok Jeon, Ji-Ye Kee, Dae-Seung Kim, Yo-Han Han, Sung-Hoon Kim, Su-Jin Kim, Jae-Young Um, Seung-Heon Hong

Published in: BMC Complementary Medicine and Therapies | Issue 1/2015

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Abstract

Background

Ixeris dentata Nakai has been used for the treatment of mithridatism, calculous, indigestion, pneumonia, hepatitis, and tumors in Korea, China, and Japan. However, the effect of a water extract of Ixeris dentata (ID) and its molecular mechanism on allergic inflammation has not been elucidated. In this study, we attempted to evaluate the effects of ID and its major compound caffeic acid on allergic inflammation in vivo and in vitro.

Methods

ID was applied to 2, 4-dinitrofluorobenzene (DNFB)-induced atopic dermatitis (AD)-like skin lesion mice and immune cell infiltration, cytokine production, and the activation of mitogen-activated protein kinases (MAPKs) were investigated. Moreover, the effect of ID on compound 48/80-induced anaphylactic shock was investigated in a mouse model. The human keratinocyte cell line (HaCaT cells) and human mast cells (HMC-1) were treated with ID or caffeic acid to investigate the effects on the production of chemokines and proinflammatory cytokines and on the activation of MAPKs.

Results

ID inhibited the serum levels of IgE and interleukin (IL)-1β in DNFB-induced AD-like skin lesion mouse models and suppressed anaphylactic shock in the mouse models. ID and caffeic acid inhibited the production of chemokines and adhesion molecules in HaCaT cells. In addition, ID reduced the release of tumor necrosis factor-α and IL-8 via the inhibition of MAPKs phosphorylation in HMC-1 cells.

Conclusions

These results suggest that ID is a potential therapeutic agent for allergic inflammatory diseases, including dermatitis.
Literature
3.
go back to reference Bonness S, Bieber T. Molecular basis of atopic dermatitis. Curr Opin Allergy Clin Immunol. 2007;7:382–6.CrossRefPubMed Bonness S, Bieber T. Molecular basis of atopic dermatitis. Curr Opin Allergy Clin Immunol. 2007;7:382–6.CrossRefPubMed
4.
go back to reference Novak N. New insights into the mechanism and management of allergic diseases: atopic dermatitis. Allergy. 2009;64:265–75.CrossRefPubMed Novak N. New insights into the mechanism and management of allergic diseases: atopic dermatitis. Allergy. 2009;64:265–75.CrossRefPubMed
5.
go back to reference Ahn EM, Bang MH, Song MC, Park MH, Kim HY, Kwon BM, et al. Cytotoxic and ACAT-inhibitory sesquiterpene lactones from the root of Ixeris dentata forma albiflora. Arch Pharm Res. 2006;29:937–41.CrossRefPubMed Ahn EM, Bang MH, Song MC, Park MH, Kim HY, Kwon BM, et al. Cytotoxic and ACAT-inhibitory sesquiterpene lactones from the root of Ixeris dentata forma albiflora. Arch Pharm Res. 2006;29:937–41.CrossRefPubMed
6.
go back to reference Oh SH, Sung TH, Kim MR. Ixeris dentata extract maintains glutathione concentrations in mouse brain tissue under oxidative stress induced by kainic acid. J Med Food. 2003;6:353–8.CrossRefPubMed Oh SH, Sung TH, Kim MR. Ixeris dentata extract maintains glutathione concentrations in mouse brain tissue under oxidative stress induced by kainic acid. J Med Food. 2003;6:353–8.CrossRefPubMed
7.
go back to reference Lee HY, Lee GH, Kim HK, Kim SH, Kp P, Chae HJ, et al. Ixeris dentata-induced regulation of amylase synthesis and secretion in glucose-treated human salivary gland cells. Food Chem Toxicol. 2013;62:739–49.CrossRefPubMed Lee HY, Lee GH, Kim HK, Kim SH, Kp P, Chae HJ, et al. Ixeris dentata-induced regulation of amylase synthesis and secretion in glucose-treated human salivary gland cells. Food Chem Toxicol. 2013;62:739–49.CrossRefPubMed
8.
go back to reference Kim DS, Ko JH, Jeon YD, Han YH, Kim HJ, Poudel A, et al. Ixeris dentata NAKAI Reduces Clinical Score and HIF-1 Expression in Experimental Colitis in Mice. Evid Based Complement Alternat Med. 2013;2013:671281.PubMedPubMedCentral Kim DS, Ko JH, Jeon YD, Han YH, Kim HJ, Poudel A, et al. Ixeris dentata NAKAI Reduces Clinical Score and HIF-1 Expression in Experimental Colitis in Mice. Evid Based Complement Alternat Med. 2013;2013:671281.PubMedPubMedCentral
9.
go back to reference Kim SB, Kang OH, Joung DK, Mun SH, Seo YS, Cha MR, et al. Anti-inflammatory effects of tectroside on UVB-induced HaCaT cells. Int J Mol Med. 2013;31:1471–6.PubMed Kim SB, Kang OH, Joung DK, Mun SH, Seo YS, Cha MR, et al. Anti-inflammatory effects of tectroside on UVB-induced HaCaT cells. Int J Mol Med. 2013;31:1471–6.PubMed
10.
go back to reference Yi JM, Hong SH, Lee HJ, Won JH, Kim JM, Jeong DM, et al. Ixeris dentata green sap inhibits both compound 48/80-induced aanaphylaxis-like response and IgE-mediated anaphylactic response in murine model. Biol Pharm Bull. 2002;25:5–9.CrossRefPubMed Yi JM, Hong SH, Lee HJ, Won JH, Kim JM, Jeong DM, et al. Ixeris dentata green sap inhibits both compound 48/80-induced aanaphylaxis-like response and IgE-mediated anaphylactic response in murine model. Biol Pharm Bull. 2002;25:5–9.CrossRefPubMed
11.
go back to reference Park EK, Sung JH, Trinh HT, Bae EA, Yun HK, Hong SS, et al. Lactic acid bacterial fermentation increases the antiallergic effects of Ixeris dentata. J Microbiol Biotechnol. 2008;18:308–13.PubMed Park EK, Sung JH, Trinh HT, Bae EA, Yun HK, Hong SS, et al. Lactic acid bacterial fermentation increases the antiallergic effects of Ixeris dentata. J Microbiol Biotechnol. 2008;18:308–13.PubMed
12.
go back to reference Albanesi C. Keratinocytes in allergic skin diseases. Curr Opin Allergy Clin Immunol. 2010;10:452–6.CrossRefPubMed Albanesi C. Keratinocytes in allergic skin diseases. Curr Opin Allergy Clin Immunol. 2010;10:452–6.CrossRefPubMed
13.
go back to reference Pastore S, Lulli D, Potapovich AI, Fidanza P, Kostyuk VA, Dellambra E, et al. Differential modulation of stress-inflammation responses by plant polyphenols in cultured normal human keratinocytes and immortalized HaCaT cells. J Dermatol Sci. 2011;63:104–14.PubMed Pastore S, Lulli D, Potapovich AI, Fidanza P, Kostyuk VA, Dellambra E, et al. Differential modulation of stress-inflammation responses by plant polyphenols in cultured normal human keratinocytes and immortalized HaCaT cells. J Dermatol Sci. 2011;63:104–14.PubMed
14.
go back to reference Albanesi C, Scarponi C, Cavani A, Federici M, Nasorri F, Girolomoni G. Interleukin-17 is produced by both Th1 and Th2 lymphocytes, and modulates interferon-gamma- and interleukin-4-induced activation of human keratinocytes. J Invest Dermatol. 2000;115:81–7.CrossRefPubMed Albanesi C, Scarponi C, Cavani A, Federici M, Nasorri F, Girolomoni G. Interleukin-17 is produced by both Th1 and Th2 lymphocytes, and modulates interferon-gamma- and interleukin-4-induced activation of human keratinocytes. J Invest Dermatol. 2000;115:81–7.CrossRefPubMed
15.
go back to reference Saeki H, Tamaki K. Thymus and activation regulated chemokine (TARC)/CCL17 and skin diseases. J Dermatol Sci. 2006;43:75–84.CrossRefPubMed Saeki H, Tamaki K. Thymus and activation regulated chemokine (TARC)/CCL17 and skin diseases. J Dermatol Sci. 2006;43:75–84.CrossRefPubMed
16.
go back to reference Hijnen D, De Bruin-Weller M, Oosting B, Lebre C, De Jong E, Bruijnzeel-Koomen C, et al. Serum thymus and activation-regulated chemokine (TARC) and cutaneous T cell- attracting chemokine (CTACK) levels in allergic diseases: TARC and CTACK are disease-specific markers for atopic dermatitis. J Allergy Clin Immunol. 2004;113:334–40.CrossRefPubMed Hijnen D, De Bruin-Weller M, Oosting B, Lebre C, De Jong E, Bruijnzeel-Koomen C, et al. Serum thymus and activation-regulated chemokine (TARC) and cutaneous T cell- attracting chemokine (CTACK) levels in allergic diseases: TARC and CTACK are disease-specific markers for atopic dermatitis. J Allergy Clin Immunol. 2004;113:334–40.CrossRefPubMed
17.
go back to reference Leung TF, Ma KC, Hon KL, Lam CW, Wan H, Li CY, et al. Serum concentration of macrophage-derived chemokine may be a useful inflammatory marker for assessing severity of atopic dermatitis in infants and young children. Pediatr Allergy Immunol. 2003;14:296–301.CrossRefPubMed Leung TF, Ma KC, Hon KL, Lam CW, Wan H, Li CY, et al. Serum concentration of macrophage-derived chemokine may be a useful inflammatory marker for assessing severity of atopic dermatitis in infants and young children. Pediatr Allergy Immunol. 2003;14:296–301.CrossRefPubMed
18.
go back to reference Galli SJ, Kalesnikoff J, Grimbaldeston MA, Piliponsky AM, Williams CM, Tsai M. Mast cells as "tunable" effector and immunoregulatory cells: recent advances. Annu Rev Immunol. 2005;23:749–86.CrossRefPubMed Galli SJ, Kalesnikoff J, Grimbaldeston MA, Piliponsky AM, Williams CM, Tsai M. Mast cells as "tunable" effector and immunoregulatory cells: recent advances. Annu Rev Immunol. 2005;23:749–86.CrossRefPubMed
19.
go back to reference Galli SJ, Tsai M. Mast cells in allergy and infection: versatile effector and regulatory cells in innate and adaptive immunity. Eur J Immunol. 2010;40:1843–51.CrossRefPubMedPubMedCentral Galli SJ, Tsai M. Mast cells in allergy and infection: versatile effector and regulatory cells in innate and adaptive immunity. Eur J Immunol. 2010;40:1843–51.CrossRefPubMedPubMedCentral
21.
go back to reference Finco TS, Baldwin AS. Mechanistic aspects of NF-kappa B regulation: the emerging role of phosphorylation and proteolysis. Immunity. 1995;3:263–72.CrossRefPubMed Finco TS, Baldwin AS. Mechanistic aspects of NF-kappa B regulation: the emerging role of phosphorylation and proteolysis. Immunity. 1995;3:263–72.CrossRefPubMed
22.
go back to reference Barnes PJ, Karin M. Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med. 1997;336:1066–71.CrossRefPubMed Barnes PJ, Karin M. Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med. 1997;336:1066–71.CrossRefPubMed
24.
go back to reference Johnson GL, Lapadat R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science. 2002;298:1911–2.CrossRefPubMed Johnson GL, Lapadat R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science. 2002;298:1911–2.CrossRefPubMed
25.
go back to reference Hommes DW, Peppelenbosch MP, van Deventer SJ. Mitogen activated protein (MAP) kinase signal transduction pathways and novel anti-inflammatory targets. Gut. 2003;52:144–51.CrossRefPubMedPubMedCentral Hommes DW, Peppelenbosch MP, van Deventer SJ. Mitogen activated protein (MAP) kinase signal transduction pathways and novel anti-inflammatory targets. Gut. 2003;52:144–51.CrossRefPubMedPubMedCentral
26.
27.
go back to reference Arthur JS, Ley SC. Mitogen-activated protein kinases in innate immunity. Nat Rev Immunol. 2013;13:679–92.CrossRefPubMed Arthur JS, Ley SC. Mitogen-activated protein kinases in innate immunity. Nat Rev Immunol. 2013;13:679–92.CrossRefPubMed
28.
go back to reference Kim SJ, Kee JY, Choi IY, Kim MC, Kim DS, Jeon YD, et al. Insamhodo-tang, a traditional Korean medicine, regulates mast cell-mediated allergic inflammation in vivo and in vitro. J Ethnopharmacol. 2011;134:339–47.CrossRefPubMed Kim SJ, Kee JY, Choi IY, Kim MC, Kim DS, Jeon YD, et al. Insamhodo-tang, a traditional Korean medicine, regulates mast cell-mediated allergic inflammation in vivo and in vitro. J Ethnopharmacol. 2011;134:339–47.CrossRefPubMed
29.
go back to reference Gould HJ, Sutton BJ, Beavil AJ, Beavil RL, McCloskey N, Coker HA, et al. The biology of IGE and the basis of allergic disease. Annu Rev Immunol. 2003;21:579–628.CrossRefPubMed Gould HJ, Sutton BJ, Beavil AJ, Beavil RL, McCloskey N, Coker HA, et al. The biology of IGE and the basis of allergic disease. Annu Rev Immunol. 2003;21:579–628.CrossRefPubMed
30.
go back to reference Cohen DE, Heidary N. Treatment of irritant and allergic contact dermatitis. Dermatol Ther. 2004;17:334–40.CrossRefPubMed Cohen DE, Heidary N. Treatment of irritant and allergic contact dermatitis. Dermatol Ther. 2004;17:334–40.CrossRefPubMed
31.
go back to reference Tan HY, Zhang AL, Chen D, Xue CC, Lenon GB. Chinese herbal medicine for atopic dermatitis: a systematic review. J Am Acad Dermatol. 2013;69:295–304.CrossRefPubMed Tan HY, Zhang AL, Chen D, Xue CC, Lenon GB. Chinese herbal medicine for atopic dermatitis: a systematic review. J Am Acad Dermatol. 2013;69:295–304.CrossRefPubMed
32.
go back to reference Yamashita H, Tanaka H, Inagaki N. Treatment of the chronic itch of atopic dermatitis using standard drugs and kampo medicines. Biol Pharm Bull. 2013;36:1253–7.CrossRefPubMed Yamashita H, Tanaka H, Inagaki N. Treatment of the chronic itch of atopic dermatitis using standard drugs and kampo medicines. Biol Pharm Bull. 2013;36:1253–7.CrossRefPubMed
33.
go back to reference Honda T, Egawa G, Grabbe S, Kabashima K. Update of immune events in the murine contact hypersensitivity model: toward the understanding of allergic contact dermatitis. J Invest Dermatol. 2013;133:303–15.CrossRefPubMed Honda T, Egawa G, Grabbe S, Kabashima K. Update of immune events in the murine contact hypersensitivity model: toward the understanding of allergic contact dermatitis. J Invest Dermatol. 2013;133:303–15.CrossRefPubMed
34.
35.
go back to reference Liu FT, Goodarzi H, Chen HY. IgE, mast cells, and eosinophils in atopic dermatitis. Clin Rev Allergy Immunol. 2011;41:298–310.CrossRefPubMed Liu FT, Goodarzi H, Chen HY. IgE, mast cells, and eosinophils in atopic dermatitis. Clin Rev Allergy Immunol. 2011;41:298–310.CrossRefPubMed
36.
go back to reference Watanabe H, Gaide O, Pétrilli V, Martinon F, Contassot E, Roques S, et al. Activation of the IL-1beta-processing inflammasome is involved in contact hypersensitivity. J Invest Dermatol. 2007;127:1956–63.CrossRefPubMed Watanabe H, Gaide O, Pétrilli V, Martinon F, Contassot E, Roques S, et al. Activation of the IL-1beta-processing inflammasome is involved in contact hypersensitivity. J Invest Dermatol. 2007;127:1956–63.CrossRefPubMed
37.
go back to reference Tasaka K, Mio M, Okamoto M. Intracellular calcium release induced by histamine releasers and its inhibition by some antiallergic drugs. Ann Allergy. 1986;56:464–9.PubMed Tasaka K, Mio M, Okamoto M. Intracellular calcium release induced by histamine releasers and its inhibition by some antiallergic drugs. Ann Allergy. 1986;56:464–9.PubMed
38.
go back to reference Boukamp P, Petrussevska RT, Breitkreutz D, Hornung J, Markham A, Fusenig NE. Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. J Cell Biol. 1988;106:761–71.CrossRefPubMed Boukamp P, Petrussevska RT, Breitkreutz D, Hornung J, Markham A, Fusenig NE. Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. J Cell Biol. 1988;106:761–71.CrossRefPubMed
39.
go back to reference Horikawa T, Nakayama T, Hikita I, Yamada H, Fujisawa R, Bito T, et al. IFN-gamma-inducible expression of thymus and activation-regulated chemokine/CCL17 and macrophage-derived chemokine/CCL22 in epidermal keratinocytes and their roles in atopic dermatitis. Int Immunol. 2002;14:767–73.CrossRefPubMed Horikawa T, Nakayama T, Hikita I, Yamada H, Fujisawa R, Bito T, et al. IFN-gamma-inducible expression of thymus and activation-regulated chemokine/CCL17 and macrophage-derived chemokine/CCL22 in epidermal keratinocytes and their roles in atopic dermatitis. Int Immunol. 2002;14:767–73.CrossRefPubMed
40.
go back to reference Sebastiani S, Albanesi C, De PO, Puddu P, Cavani A, Girolomoni G. The role of chemokines in allergic contact dermatitis. Arch Dermatol Res. 2002;293:552–9.CrossRefPubMed Sebastiani S, Albanesi C, De PO, Puddu P, Cavani A, Girolomoni G. The role of chemokines in allergic contact dermatitis. Arch Dermatol Res. 2002;293:552–9.CrossRefPubMed
41.
go back to reference Navi D, Saegusa J, Liu FT. Mast cells and immunological skin diseases. Clin Rev Allergy Immunol. 2007;33:144–55.CrossRefPubMed Navi D, Saegusa J, Liu FT. Mast cells and immunological skin diseases. Clin Rev Allergy Immunol. 2007;33:144–55.CrossRefPubMed
42.
go back to reference Hamann K, Grabbe J, Welker P, Haas N, Algermissen B, Czarnetzki BM. Phenotypic evaluation of cultured human mast and basophilic cells and of normal human skin mast cells. Arch Dermatol Res. 1994;286:380–5.CrossRefPubMed Hamann K, Grabbe J, Welker P, Haas N, Algermissen B, Czarnetzki BM. Phenotypic evaluation of cultured human mast and basophilic cells and of normal human skin mast cells. Arch Dermatol Res. 1994;286:380–5.CrossRefPubMed
43.
go back to reference de Haij S, Bakker AC, van der Geest RN, Haegeman G, Vanden Berghe W, Aarbiou J, et al. NF-kappaB mediated IL-6 production by renal epithelial cells is regulated by c-jun NH2-terminal kinase. J Am Soc Nephrol. 2005;16:1603–11.CrossRefPubMed de Haij S, Bakker AC, van der Geest RN, Haegeman G, Vanden Berghe W, Aarbiou J, et al. NF-kappaB mediated IL-6 production by renal epithelial cells is regulated by c-jun NH2-terminal kinase. J Am Soc Nephrol. 2005;16:1603–11.CrossRefPubMed
45.
go back to reference Cha MR, Choi YH, Choi CW, Yoo DS, Kim YS, Choi SU, et al. New guaiane sesquiterpene lactones from Ixeris dentata. Planta Med. 2011;77:380–2.CrossRefPubMed Cha MR, Choi YH, Choi CW, Yoo DS, Kim YS, Choi SU, et al. New guaiane sesquiterpene lactones from Ixeris dentata. Planta Med. 2011;77:380–2.CrossRefPubMed
46.
go back to reference Karki S, Park HJ, Nugroho A, Kim EJ, Jung HA, Choi JS. Quantification of major compounds from Ixeris dentata, Ixeris dentata Var. albiflora, and Ixeris sonchifolia and their comparative anti-inflammatory activity in lipopolysaccharide-stimulated RAW 264.7 cells. J Med Food. 2015;18:83–94.CrossRefPubMed Karki S, Park HJ, Nugroho A, Kim EJ, Jung HA, Choi JS. Quantification of major compounds from Ixeris dentata, Ixeris dentata Var. albiflora, and Ixeris sonchifolia and their comparative anti-inflammatory activity in lipopolysaccharide-stimulated RAW 264.7 cells. J Med Food. 2015;18:83–94.CrossRefPubMed
47.
go back to reference Kritas SK, Saggini A, Varvara G, Murmura G, Caraffa A, Antinolfi P, et al. Luteolin inhibits mast cell-mediated allergic inflammation. J Biol Regul Homeost Agents. 2013;27:955–9.PubMed Kritas SK, Saggini A, Varvara G, Murmura G, Caraffa A, Antinolfi P, et al. Luteolin inhibits mast cell-mediated allergic inflammation. J Biol Regul Homeost Agents. 2013;27:955–9.PubMed
48.
go back to reference Kwon OS, Choi JS, Islam MN, Kim YS, Kim HP. Inhibition of 5-lipoxygenase and skin inflammation by the aerial parts of Artemisia capillaris and its constituents. Arch Pharm Res. 2011;34:1561–9.CrossRefPubMed Kwon OS, Choi JS, Islam MN, Kim YS, Kim HP. Inhibition of 5-lipoxygenase and skin inflammation by the aerial parts of Artemisia capillaris and its constituents. Arch Pharm Res. 2011;34:1561–9.CrossRefPubMed
49.
go back to reference Trinh HT, Bae EA, Hyun YJ, Jang YA, Yun HK, Hong SS, et al. Anti-allergic effects of fermented Ixeris sonchifolia and its constituent in mice. J Microbiol Biotechnol. 2010;20:217–23.PubMed Trinh HT, Bae EA, Hyun YJ, Jang YA, Yun HK, Hong SS, et al. Anti-allergic effects of fermented Ixeris sonchifolia and its constituent in mice. J Microbiol Biotechnol. 2010;20:217–23.PubMed
50.
go back to reference Zhang M, Zhou J, Wang L, Li B, Guo J, Guan X, et al. Caffeic acid reduces cutaneous tumor necrosis factor alpha (TNF-α), IL-6 and IL-1β levels and ameliorates skin edema in acute and chronic model of cutaneous inflammation in mice. Biol Pharm Bull. 2014;37:347–54.CrossRefPubMed Zhang M, Zhou J, Wang L, Li B, Guo J, Guan X, et al. Caffeic acid reduces cutaneous tumor necrosis factor alpha (TNF-α), IL-6 and IL-1β levels and ameliorates skin edema in acute and chronic model of cutaneous inflammation in mice. Biol Pharm Bull. 2014;37:347–54.CrossRefPubMed
51.
go back to reference Hossen MA, Inoue T, Shinmei Y, Minami K, Fujii Y, Kamei C. Caffeic acid inhibits compound 48/80-induced allergic symptoms in mice. Biol Pharm Bull. 2006;29:64–6.CrossRefPubMed Hossen MA, Inoue T, Shinmei Y, Minami K, Fujii Y, Kamei C. Caffeic acid inhibits compound 48/80-induced allergic symptoms in mice. Biol Pharm Bull. 2006;29:64–6.CrossRefPubMed
52.
go back to reference Harvima IT. Induction of matrix metalloproteinase-9 in keratinocytes by histamine. J Invest Dermatol. 2008;128:2748–50.CrossRefPubMed Harvima IT. Induction of matrix metalloproteinase-9 in keratinocytes by histamine. J Invest Dermatol. 2008;128:2748–50.CrossRefPubMed
Metadata
Title
Effects of Ixeris dentata water extract and caffeic acid on allergic inflammation in vivo and in vitro
Authors
Yong-Deok Jeon
Ji-Ye Kee
Dae-Seung Kim
Yo-Han Han
Sung-Hoon Kim
Su-Jin Kim
Jae-Young Um
Seung-Heon Hong
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2015
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-015-0700-x

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