Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2016

Open Access 01-12-2016 | Research article

Douchi (fermented Glycine max Merr.) alleviates atopic dermatitis-like skin lesions in NC/Nga mice by regulation of PKC and IL-4

Authors: A-Ram Jung, Sang-hyun Ahn, In-Sik Park, Sun-Young Park, Seung-Il Jeong, Jin-Hong Cheon, Kibong Kim

Published in: BMC Complementary Medicine and Therapies | Issue 1/2016

Login to get access

Abstract

Background

Douchi (fermented Glycine max Merr.) is produced from fermented soybeans, which is widely used in traditional herbal medicine. In this study, we investigated whether Douchi attenuates protein kinase C (PKC) and interleukin (IL)-4 response and cutaneous inflammation in Atopic dermatitis (AD)-like NC/Nga mice.

Methods

To induce AD-like skin lesions, D. farinae antigen was applied to the dorsal skin of 3-week-old NC/Nga mice. After inducing AD, Douchi extract was administered 20 mg/kg daily for 3 weeks to the Douchi-treated mice group. We identified the changes of skin barrier and Th2 differentiation through PKC and IL-4 by immunohistochemistry.

Results

Douchi treatment of NC/Nga mice significantly reduced clinical scores (p < 0.01) and histological features. The levels of PKC and IL-4 were significantly reduced in the Douchi-treated group (p < 0.01). The reduction of IL-4 and PKC led to decrease of inflammatory factors such as substance P, inducible nitric oxide synthase (iNOS) and Matrix metallopeptidase 9 (MMP-9) (all p < 0.01). Douchi also down-regulated Th1 markers (IL-12, TNF-α) as well as Th2 markers (IL-4, p-IκB) (p < 0.01).

Conclusion

Douchi alleviates AD-like skin lesions through suppressing of PKC and IL-4. These results also lead to diminish levels of substance P, iNOS and MMP-9 in skin lesions. Therefore, Douchi may have potential applications for the prevention and treatment of AD.
Literature
1.
2.
Bantz SK, Zhu Z, Zheng T. The Atopic March: Progression from Atopic Dermatitis to Allergic Rhinitis and Asthma. J Clin Cell Immunol. 2014;5(2).
3.
Georas SN, Guo J, De Fanis U, Casolaro V. T-helper cell type-2 regulation in allergic disease. Eur Respir J. 2005;26(6):1119–37.CrossRefPubMed
4.
5.
Chan LS, Robinson N, Xu L. 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. J Investig Dermatol. 2001;117(4):977–83.CrossRefPubMed
6.
Renz H, Jujo K, Bradley KL, Domenico J, Gelfand EW, Leung DY. Enhanced IL-4 production and IL-4 receptor expression in atopic dermatitis and their modulation by interferon-gamma. J Investig Dermatol. 1992;99(4):403–8.CrossRefPubMed
7.
Ochi H, De Jesus NH, Hsieh FH, Austen KF, Boyce JA. IL-4 and -5 prime human mast cells for different profiles of IgE-dependent cytokine production. Proc Natl Acad Sci U S A. 2000;97(19):10509–13.CrossRefPubMedPubMedCentral
8.
Lacraz S, Nicod L, Galve-de Rochemonteix B, Baumberger C, Dayer JM, Welgus HG. Suppression of metalloproteinase biosynthesis in human alveolar macrophages by interleukin-4. J Clin Invest. 1992;90(2):382–8.CrossRefPubMedPubMedCentral
9.
Hiroi M, Sakaeda Y, Yamaguchi H, Ohmori Y. Anti-inflammatory cytokine interleukin-4 inhibits inducible nitric oxide synthase gene expression in the mouse macrophage cell line RAW264.7 through the repression of octamer-dependent transcription. Mediators Inflamm. 2013;2013:369693.CrossRefPubMedPubMedCentral
10.
Homey B, Steinhoff M, Ruzicka T, Leung DYM. Cytokines and chemokines orchestrate atopic skin inflammation. J Allergy Clin Immunol. 2006;118(1):178–89.CrossRefPubMed
11.
Cork MJ, Danby SG, Vasilopoulos Y, Hadgraft J, Lane ME, Moustafa M, Guy RH, Macgowan AL, Tazi-Ahnini R, Ward SJ. Epidermal barrier dysfunction in atopic dermatitis. J Invest Dermatol. 2009;129(8):1892–908.CrossRefPubMed
12.
Kim H, Zamel R, Bai XH, Liu M. PKC activation induces inflammatory response and cell death in human bronchial epithelial cells. PLoS One. 2013;8(5):e64182.CrossRefPubMedPubMedCentral
13.
Pastore S, Mascia F, Girolomoni G. The contribution of keratinocytes to the pathogenesis of atopic dermatitis. Eur J Dermatol. 2006;16(2):125–31.PubMed
14.
Robert V, Triffaux E, Paulet PE, Guery JC, Pelletier L, Savignac M. Protein kinase C-dependent activation of CaV1.2 channels selectively controls human TH2-lymphocyte functions. J Allergy Clin Immunol. 2014;133(4):1175–83.CrossRefPubMed
15.
Halonen M, Lohman IC, Stern DA, Spangenberg A, Anderson D, Mobley S, Ciano K, Peck M, Wright AL. Th1/Th2 patterns and balance in cytokine production in the parents and infants of a large birth cohort. J Immunol. 2009;182(5):3285–93.CrossRefPubMed
16.
Hengge UR, Ruzicka T, Schwartz RA, Cork MJ. Adverse effects of topical glucocorticosteroids. J Am Acad Dermatol. 2006;54(1):1–15.CrossRefPubMed
17.
Wu D, Huang C, Mo X, Liu J, Cai J, Liu C, Zhu H, Li H, Chen D. Development and initial validation of a Traditional Chinese Medicine symptom-specific outcome measure: a Zheng-related atopic dermatitis symptom questionnaire (ZRADSQ). Health Qual Life Outcomes. 2013;11:212.CrossRefPubMedPubMedCentral
18.
Hsu CH, Yu MC, Lee CH, Lee TC, Yang SY. High eosinophil cationic protein level in asthmatic patients with “heat” Zheng. Am J Chin Med. 2003;31(2):277–83.CrossRefPubMed
19.
Li S, Zhang ZQ, Wu LJ, Zhang XG, Li YD, Wang YY. Understanding ZHENG in traditional Chinese medicine in the context of neuro-endocrine-immune network. IET Syst Biol. 2007;1(1):51–60.CrossRefPubMed
20.
Muluye RA, Bian Y, Alemu PN. Anti-inflammatory and Antimicrobial Effects of Heat-Clearing Chinese Herbs: A Current Review. J Tradit Complement Med. 2014;4(2):93–8.CrossRefPubMedPubMedCentral
21.
Song JH, Ahn SH, Cheon JH, Park SY, Kim HH, Kim KB. Effects of Hataedock with Douchi on 2,4-dinitrofluorobenzene-induced Atopic Dermatitis-like Skin Lesion in NC/Nga Mice. J Physiol Pathol Korean Med. 2016;30(2):109–15.CrossRef
22.
Zhang JH, Tatsumi E, Ding CH, Li LT. Angiotensin I-converting enzyme inhibitory peptides in douchi, a Chinese traditional fermented soybean product. Food Chem. 2006;3:551–7.CrossRef
23.
Lin J, Xu Y, Zhao T, Sun L, Yang M, Liu T, Sun H, Zhang L. Genistein suppresses smooth muscle cell-derived foam cell formation through tyrosine kinase pathway. Biochem Biophys Res Commun. 2015;463(4):1297–304.CrossRefPubMed
24.
Nazir N, Koul S, Qurishi MA, Taneja SC, Ahmad SF, Khan B, Bani S, Qazi GN. Immunomodulatory activity of isoflavones isolated from Iris germanica (Iridaceae) on T-lymphocytes and cytokines. Phytother Res. 2009;23(3):428–33.CrossRefPubMed
25.
Bao ZS, Hong L, Guan Y, Dong XW, Zheng HS, Tan GL, Xie QM. Inhibition of airway inflammation, hyperresponsiveness and remodeling by soy isoflavone in a murine model of allergic asthma. Int Immunopharmacol. 2011;11(8):899–906.CrossRefPubMed
26.
Kim JH, Jia Y, Lee JG, Nam B, Lee JH, Shin KS, Hurh BS, Choi YH, Lee SJ. Hypolipidemic and antiinflammation activities of fermented soybean fibers from meju in C57BL/6 J mice. Phytother Res. 2014;28(9):1335–41.CrossRefPubMed
27.
Matsuda A, Tanaka A, Pan W, Okamoto N, Oida K, Kingyo N, Amagai Y, Xia Y, Jang H, Nishikawa S, et al. Supplementation of the fermented soy product ImmuBalance effectively reduces itching behavior of atopic NC/Tnd mice. J Dermatol Sci. 2012;67(2):130–9.CrossRefPubMed
28.
van Diepen JA, Berbee JF, Havekes LM, Rensen PC. Interactions between inflammation and lipid metabolism: relevance for efficacy of anti-inflammatory drugs in the treatment of atherosclerosis. Atherosclerosis. 2013;228(2):306–15.CrossRefPubMed
29.
Wang L, Li D, Zou L, Chen XD, Cheng YQ, Yamaki K. Antioxidative activity of Douchi (a Chinese traditional salt-fermented soybean food) extracts during its processing. Int J Food Prop. 2007;10(2):385–96.CrossRef
30.
Wang D, Wang L-j, Zhu F-x, Zhu J-y, Chen XD, Zou L, Saito M, Li L-t. In vitro and in vivo studies on the antioxidant activities of the aqueous extracts of Douchi (a traditional Chinese salt-fermented soybean food). Food Chem. 2008;107(4):1421–8.CrossRef
31.
32.
Sung YY, Yoon T, Jang JY, Park SJ, Kim HK. Topical application of Rehmannia glutinosa extract inhibits mite allergen-induced atopic dermatitis in NC/Nga mice. J Ethnopharmacol. 2011;134(1):37–44.CrossRefPubMed
33.
Choi SE, Park KH, Jeong MS, Kim HH, Lee DI, Joo SS, Lee CS, Bang H, Choi YW, Lee MK, et al. Effect of Alnus japonica extract on a model of atopic dermatitis in NC/Nga mice. J Ethnopharmacol. 2011;136(3):406–13.CrossRefPubMed
34.
Lee H, Lee JK, Ha H, Lee MY, Seo CS, Shin HK. Angelicae Dahuricae Radix Inhibits Dust Mite Extract-Induced Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice. Evid Based Complement Alternat Med. 2012;2012:743075.PubMedPubMedCentral
35.
Sung YY, Yoon T, Jang JY, Park SJ, Jeong GH, Kim HK. Inhibitory effects of Cinnamomum cassia extract on atopic dermatitis-like skin lesions induced by mite antigen in NC/Nga mice. J Ethnopharmacol. 2011;133(2):621–8.CrossRefPubMed
36.
Leung DYM, Hirsch RL, Schneider L, Moody C, Takaoka R, Li SH, Meyerson LA, Mariam SG, Goldstein G, Hanifin JM. Thymopentin therapy reduces the clinical severity of atopic dermatitis. J Allergy Clin Immunol. 1990;85(5):927–33.CrossRefPubMed
37.
Hill JR, Wertz PW. Molecular models of the intercellular lipid lamellae from epidermal stratum corneum. Biochim Biophys Acta. 2003;1616(2):121–6.CrossRefPubMed
38.
Shelburne CP, Ryan JJ. The role of Th2 cytokines in mast cell homeostasis. Immunol Rev. 2001;179:82–93.CrossRefPubMed
39.
O’Connor TM, O’Connell J, O’Brien DI, Goode T, Bredin CP, Shanahan F. The role of substance P in inflammatory disease. J Cell Physiol. 2004;201(2):167–80.CrossRefPubMed
40.
Leung DYM. Atopic dermatitis: The skin as a window into the pathogenesis of chronic allergic diseases. J Allergy Clin Immunol. 1995;96(3):302–19.CrossRefPubMed
41.
Matsusaka T, Fujikawa K, Nishio Y, Mukaida N, Matsushima K, Kishimoto T, Akira S. Transcription factors NF-IL6 and NF-kappa B synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8. Proc Natl Acad Sci U S A. 1993;90(21):10193–7.CrossRefPubMedPubMedCentral
42.
Tanaka A, Muto S, Jung K, Itai A, Matsuda H. Topical application with a new NF-kappaB inhibitor improves atopic dermatitis in NC/NgaTnd mice. J Invest Dermatol. 2007;127(4):855–63.CrossRefPubMed
43.
Viatour P, Merville MP, Bours V, Chariot A. Phosphorylation of NF-kappaB and IkappaB proteins: implications in cancer and inflammation. Trends Biochem Sci. 2005;30(1):43–52.CrossRefPubMed
44.
Harskamp CT, Armstrong AW. Immunology of atopic dermatitis: novel insights into mechanisms and immunomodulatory therapies. Semin Cutan Med Surg. 2013;32(3):132–9.CrossRefPubMed
45.
Esaki H, Shirasaki T, Yamashita K, Nakamura Y, Kawakishi S, Osawa T. Absorption and excretion of the 8-hydroxydaidzein in rats after oral administration and its antioxidant effect. J Nutr Sci Vitaminol (Tokyo). 2005;51(2):80–6.CrossRef
46.
Kim JG. Antigenotoxic effects of water extract from Korean fermented soybean paste (doen-jang). J Food Prot. 2004;67(1):156–61.CrossRefPubMed
47.
Fujita H, Yamagami T. Absence of mutagenicity, genotoxicity, and subchronic oral toxicity of Touchi extract. Int J Toxicol. 2007;26(5):465–73.CrossRefPubMed
48.
Matsuoka H, Maki N, Yoshida S, Arai M, Wang J, Oikawa Y, Ikeda T, Hirota N, Nakagawa H, Ishii A. A mouse model of the atopic eczema/dermatitis syndrome by repeated application of a crude extract of house-dust mite Dermatophagoides farinae. Allergy. 2003;58(2):139–45.CrossRefPubMed
49.
Hogan MB, Peele K, Wilson NW. Skin barrier function and its importance at the start of the atopic march. J Allergy (Cairo). 2012;2012:901940.
50.
Fox TE, Houck KL, O’Neill SM, Nagarajan M, Stover TC, Pomianowski PT, Unal O, Yun JK, Naides SJ, Kester M. Ceramide recruits and activates protein kinase C zeta (PKC zeta) within structured membrane microdomains. J Biol Chem. 2007;282(17):12450–7.CrossRefPubMed
51.
52.
Baram D, Vaday GG, Salamon P, Drucker I, Hershkoviz R, Mekori YA. Human mast cells release metalloproteinase-9 on contact with activated T cells: juxtacrine regulation by TNF-alpha. J Immunol. 2001;167(7):4008–16.CrossRefPubMed
53.
Matsuda H, Kawakita K, Kiso Y, Nakano T, Kitamura Y. Substance P induces granulocyte infiltration through degranulation of mast cells. J Immunol. 1989;142(3):927–31.PubMed
54.
Ohmura T, Hayashi T, Satoh Y, Konomi A, Jung B, Satoh H. Involvement of substance P in scratching behaviour in an atopic dermatitis model. Eur J Pharmacol. 2004;491(2-3):191–4.CrossRefPubMed
55.
Wang P, Wu P, Siegel MI, Egan RW, Billah MM. Interleukin (IL)-10 inhibits nuclear factor kappa B (NF kappa B) activation in human monocytes. IL-10 and IL-4 suppress cytokine synthesis by different mechanisms. J Biol Chem. 1995;270(16):9558–63.CrossRefPubMed
56.
Davis RL, Sanchez AC, Lindley DJ, Williams SC, Syapin PJ. Effects of mechanistically distinct NF-kappaB inhibitors on glial inducible nitric-oxide synthase expression. Nitric Oxide. 2005;12(4):200–9.CrossRefPubMed
57.
Kwak CS, Lee MS, Park SC. Higher antioxidant properties of Chungkookjang, a fermented soybean paste, may be due to increased aglycone and malonylglycoside isoflavone during fermentation. Nutr Res. 2007;27(11):719–27.CrossRef
58.
Duan W, Kuo IC, Selvarajan S, Chua KY, Bay BH, Wong WS. Antiinflammatory effects of genistein, a tyrosine kinase inhibitor, on a guinea pig model of asthma. Am J Respir Crit Care Med. 2003;167(2):185–92.CrossRefPubMed
59.
Lu H, Shi JX, Zhang DM, Wang HD, Hang CH, Chen HL, Yin HX. Inhibition of hemolysate-induced iNOS and COX-2 expression by genistein through suppression of NF-small ka, CyrillicB activation in primary astrocytes. J Neurol Sci. 2009;278(1-2):91–5.CrossRefPubMed
60.
J-h Z, Arao Y, S-j S, Kikuchi A, Kayama F. Oral administration of soy-derived genistin suppresses lipopolysaccharide-induced acute liver inflammation but does not induce thymic atrophy in the rat. Life Sci. 2006;78(8):812–9.CrossRef
61.
Oh HJ, Kang YG, Na TY, Kim HJ, Park JS, Cho WJ, Lee MO. Identification of daidzein as a ligand of retinoic acid receptor that suppresses expression of matrix metalloproteinase-9 in HaCaT cells. Mol Cell Endocrinol. 2013;376(1-2):107–13.CrossRefPubMed
62.
Neis MM, Peters B, Dreuw A, Wenzel J, Bieber T, Mauch C, Krieg T, Stanzel S, Heinrich PC, Merk HF, et al. Enhanced expression levels of IL-31 correlate with IL-4 and IL-13 in atopic and allergic contact dermatitis. J Allergy Clin Immunol. 2006;118(4):930–7.CrossRefPubMed
63.
Danso MO, van Drongelen V, Mulder A, van Esch J, Scott H, van Smeden J, El Ghalbzouri A, Bouwstra JA. TNF-α and Th2 Cytokines Induce Atopic Dermatitis-like Features on Epidermal Differentiation Proteins and Stratum Corneum Lipids in Human Skin Equivalents. J Invest Dermatol. 2014;134(7):1941–50.CrossRefPubMed
64.
Choi JH, Park BH, Kim HG, Hwang YP, Han EH, Jin SW, Seo JK, Chung YC, Jeong HG. Inhibitory effect of Psidium guajava water extract in the development of 2,4-dinitrochlorobenzene-induced atopic dermatitis in NC/Nga mice. Food Chem Toxicol. 2012;50(8):2923–9.CrossRefPubMed
65.
Sung YY, Kim DS, Yang WK, Nho KJ, Seo HS, Kim YS, Kim HK. Inhibitory effects of Drynaria fortunei extract on house dust mite antigen-induced atopic dermatitis in NC/Nga mice. J Ethnopharmacol. 2012;144(1):94–100.CrossRefPubMed
66.
Xu L, Du B, Xu B. A systematic, comparative study on the beneficial health components and antioxidant activities of commercially fermented soy products marketed in China. Food Chem. 2015;174:202–13.CrossRefPubMed
67.
Arora N, Shah K, Pandey-Rai S. Inhibition of imiquimod-induced psoriasis-like dermatitis in mice by herbal extracts from some Indian medicinal plants. Protoplasma. 2016;253(2):503–15.CrossRefPubMed
68.
Ben-Gashir MA, Seed PT, Hay RJ. Predictors of atopic dermatitis severity over time. J Am Acad Dermatol. 2004;50(3):349–56.CrossRefPubMed
Metadata
Title
Douchi (fermented Glycine max Merr.) alleviates atopic dermatitis-like skin lesions in NC/Nga mice by regulation of PKC and IL-4
Authors
A-Ram Jung
Sang-hyun Ahn
In-Sik Park
Sun-Young Park
Seung-Il Jeong
Jin-Hong Cheon
Kibong Kim
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2016
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-016-1394-4

Other articles of this Issue 1/2016

BMC Complementary Medicine and Therapies 1/2016 Go to the issue

Research article

Tyrosinase inhibition and antioxidant properties of Asphodelus microcarpus extracts

Research article

Immunomodulatory and anticancer potential of Gan cao (Glycyrrhiza uralensis Fisch.) polysaccharides by CT-26 colon carcinoma cell growth inhibition and cytokine IL-7 upregulation in vitro

Research article

Antiangiogenic and antihepatocellular carcinoma activities of the Juniperus chinensis extract

Research article

In-vitro alpha amylase inhibitory activity of the leaf extracts of Adenanthera pavonina

Research article

A preliminary randomised controlled study of short-term Antrodia cinnamomea treatment combined with chemotherapy for patients with advanced cancer

Research article

The Korean herbal medicine, Do In Seung Gi-Tang, attenuates atherosclerosis via AMPK in high-fat diet-induced ApoE−/− mice