Skip to main content

Advertisement

SpringerLink
Log in

Anti-inflammatory effect of bee venom in phthalic anhydride-induced atopic dermatitis animal model

  • Original Article
  • Published:
Inflammopharmacology Aims and scope Submit manuscript

Abstract

Globally, many people have been affected with atopic dermatitis (AD), a chronic inflammatory skin disease. AD is associated with multiple factors such as genetic, inflammatory, and immune factors. Bee venom (BV) is now widely used for the treatment of several inflammatory diseases. However, its effect on 5% phthalic anhydride (PA)-induced AD has not been reported yet. We investigated the anti-inflammatory and anti-AD effects of BV in a PA-induced animal model of AD. Balb/c mice were treated with topical application of 5% PA to the dorsal skin and ears for induction of AD. After 24 h, BV was applied on the back and ear skin of the mice three times a week for 4 weeks. BV treatment significantly reduced the PA-induced AD clinical score, back and ear epidermal thickness, as well as IgE level and infiltration of immune cells in the skin tissues compared to those of control mice. The levels of inflammatory cytokines in the serum were significantly decreased in BV-treated group compared to PA-treated group. In addition, BV inhibited the expression of iNOS and COX-2 as well as the activation of mitogen-activated protein kinase (MAPK) and NF-ҡB induced by PA in the skin tissues. We also found that BV abrogated the lipopolysaccharide or TNF-α/IFN-γ-induced NO production, expression of iNOS and COX-2, as well as MAPK and NF-ҡB signaling pathway in RAW 264.7 and HaCaT cells. These results suggest that BV may be a potential therapeutic macromolecule for the treatment of AD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Ahn S, Siddiqi MH, Aceituno VC et al (2016) Ginsenoside Rg5:Rk1 attenuates TNF-alpha/IFN-gamma-induced production of thymus- and activation-regulated chemokine (TARC/CCL17) and LPS-induced NO production via downregulation of NF-kappaB/p38 MAPK/STAT1 signaling in human keratinocytes and macrophages. Vitro Cell Dev Biol Anim 52:287–295

    CAS  Google Scholar 

  • Ban M, Hettich D (2005) Effect of Th2 cytokine antagonist treatments on chemical-induced allergic response in mice. J Appl Toxicol 25:239–247

    CAS  PubMed  Google Scholar 

  • Brandt EB, Sivaprasad U (2011) Th2 cytokines and atopic dermatitis. J Clin Cell Immunol 2:2011

    Google Scholar 

  • Brunner PM, Guttman-Yassky E, Leung DY (2017) The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol 139:S65–S76

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen L, Martinez O, Overbergh L, Mathieu C, Prabhakar BS, Chan LS (2004) Early up-regulation of Th2 cytokines and late surge of Th1 cytokines in an atopic dermatitis model. Clin Exp Immunol 138:375–387

    CAS  PubMed  PubMed Central  Google Scholar 

  • Choi YY, Kim MH, Lee H, Jo SY, Yang WM (2018) (R)-(+)-pulegone suppresses allergic and inflammation responses on 2,4-dinitrochlorobenzene-induced atopic dermatitis in mice model. J Dermatol Sci 91:292–300

    CAS  PubMed  Google Scholar 

  • Cohen DE, Heidary N (2004) Treatment of irritant and allergic contact dermatitis. Dermatol Ther 17:334–340

    PubMed  Google Scholar 

  • Dearman RJ, Kimber I (1992) Divergent immune responses to respiratory and contact chemical allergens: antibody elicited by phthalic anhydride and oxazolone. Clin Exp Allergy 22:241–250

    CAS  PubMed  Google Scholar 

  • Friedmann PS (2006) Contact sensitisation and allergic contact dermatitis: immunobiological mechanisms. Toxicol Lett 162:49–54

    CAS  PubMed  Google Scholar 

  • Han JH, Ju JH, Lee YS et al (2018) Astaxanthin alleviated ethanol-induced liver injury by inhibition of oxidative stress and inflammatory responses via blocking of STAT3 activity. Sci Rep 8:14090

    PubMed  PubMed Central  Google Scholar 

  • Hartmann A, Mullner J, Meier N et al (2016) Bee venom for the treatment of Parkinson disease—a randomized controlled clinical trial. PLoS ONE 11:e0158235

    PubMed  PubMed Central  Google Scholar 

  • Homey B, Steinhoff M, Ruzicka T, Leung DY (2006) Cytokines and chemokines orchestrate atopic skin inflammation. J Allergy Clin Immunol 118:178–189

    CAS  PubMed  Google Scholar 

  • Jeon YD, Kee JY, Kim DS et al (2015) Effects of Ixeris dentata water extract and caffeic acid on allergic inflammation in vivo and in vitro. BMC Complement Altern Med 15:196

    PubMed  PubMed Central  Google Scholar 

  • Ju Ho P, Jun Sung J, Ki Cheon K, Jin Tae H (2018) Anti-inflammatory effect of Centella asiatica phytosome in a mouse model of phthalic anhydride-induced atopic dermatitis. Phytomedicine 43:110–119

    PubMed  Google Scholar 

  • Jung M, Choi J, Lee SA, Kim H, Hwang J, Choi EH (2014) Pyrrolidone carboxylic acid levels or caspase-14 expression in the corneocytes of lesional skin correlates with clinical severity, skin barrier function and lesional inflammation in atopic dermatitis. J Dermatol Sci 76:231–239

    CAS  PubMed  Google Scholar 

  • Kim SY, Sohn EJ, Kim DW et al (2011) Transduced PEP-1-FK506BP ameliorates atopic dermatitis in NC/Nga mice. J Invest Dermatol 131:1477–1485

    CAS  PubMed  Google Scholar 

  • Kim IS, Kim MJ, Shin DH, Son KH, Park HY, Lee JS (2013a) Arazyme inhibits cytokine expression and upregulates skin barrier protein expression. Mol Med Rep 8:551–556

    CAS  PubMed  Google Scholar 

  • Kim KH, Lee WR, An HJ et al (2013b) Bee venom ameliorates compound 48/80-induced atopic dermatitis-related symptoms. Int J Clin Exp Pathol 6:2896–2903

    PubMed  PubMed Central  Google Scholar 

  • Kim GD, Lee SE, Park YS, Shin DH, Park GG, Park CS (2014) Immunosuppressive effects of fisetin against dinitrofluorobenzene-induced atopic dermatitis-like symptoms in NC/Nga mice. Food Chem Toxicol 66:341–349

    CAS  PubMed  Google Scholar 

  • Lee JD, Kim SY, Kim TW et al (2004) Anti-inflammatory effect of bee venom on type II collagen-induced arthritis. Am J Chin Med 32:361–367

    PubMed  Google Scholar 

  • Lee YJ, Kim JE, Kwak MH et al (2014) Quantitative evaluation of the therapeutic effect of fermented soybean products containing a high concentration of GABA on phthalic anhydride-induced atopic dermatitis in IL-4/Luc/CNS-1 Tg mice. Int J Mol Med 33:1185–1194

    CAS  PubMed  Google Scholar 

  • Lee HJ, Kim MH, Choi YY et al (2016) Improvement of atopic dermatitis with topical application of Spirodela polyrhiza. J Ethnopharmacol 180:12–17

    PubMed  Google Scholar 

  • Lee DY, Hwang CJ, Choi JY et al (2017) Inhibitory effect of carnosol on phthalic anhydride-induced atopic dermatitis via inhibition of STAT3. Biomol Ther (Seoul) 25:535–544

    CAS  PubMed Central  Google Scholar 

  • Lee YS, Lee CH, Bae JT et al (2018) Inhibition of skin carcinogenesis by suppression of NF-κB dependent ITGAV and TIMP-1 expression in IL-32γ overexpressed condition. J Exp Clin Cancer Res 37:293

    CAS  PubMed  PubMed Central  Google Scholar 

  • Leung DY (2000) Atopic dermatitis: new insights and opportunities for therapeutic intervention. J Allergy Clin Immunol 105:860–876

    CAS  PubMed  Google Scholar 

  • Li C, Maillet I, Mackowiak C et al (2017) Experimental atopic dermatitis depends on IL-33R signaling via MyD88 in dendritic cells. Cell Death Dis 8:e2735

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lim JM, Lee B, Min JH et al (2018) Effect of peiminine on DNCB-induced atopic dermatitis by inhibiting inflammatory cytokine expression in vivo and in vitro. Int Immunopharmacol 56:135–142

    CAS  PubMed  Google Scholar 

  • Man G, Hu LZ, Elias PM, Man MQ (2018) Therapeutic benefits of natural ingredients for atopic dermatitis. Chin J Integr Med 24:308–314

    CAS  PubMed  Google Scholar 

  • Neis MM, Peters B, Dreuw A et al (2006) Enhanced expression levels of IL-31 correlate with IL-4 and IL-13 in atopic and allergic contact dermatitis. J Allergy Clin Immunol 118:930–937

    CAS  PubMed  Google Scholar 

  • Ozturk AB, Bayraktar R, Gogebakan B, Mumbuc S, Bayram H (2017) Comparison of inflammatory cytokine release from nasal epithelial cells of non-atopic non-rhinitic, allergic rhinitic and polyp subjects and effects of diesel exhaust particles in vitro. Allergol Immunopathol (Madr) 45:473–481

    CAS  Google Scholar 

  • Park SJ, Lee YH, Lee KH, Kim TJ (2013) Effect of eriodictyol on the development of atopic dermatitis-like lesions in ICR mice. Biol Pharm Bull 36:1375–1379

    CAS  PubMed  Google Scholar 

  • Park JH, Kim MS, Jeong GS, Yoon J (2015) Xanthii fructus extract inhibits TNF-alpha/IFN-gamma-induced Th2-chemokines production via blockade of NF-kappaB, STAT1 and p38-MAPK activation in human epidermal keratinocytes. J Ethnopharmacol 171:85–93

    CAS  PubMed  Google Scholar 

  • Schakel K, Dobel T, Bosselmann I (2014) Future treatment options for atopic dermatitis—small molecules and beyond. J Dermatol Sci 73:91–100

    PubMed  Google Scholar 

  • Schreiber S, Kilgus O, Payer E et al (1992) Cytokine pattern of Langerhans cells isolated from murine epidermal cell cultures. J Immunol 149:3524–3534

    CAS  PubMed  Google Scholar 

  • Seo WY, Youn GS, Choi SY, Park J (2015) Butein, a tetrahydroxychalcone, suppresses pro-inflammatory responses in HaCaT keratinocytes. BMB Rep 48:495–500

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sredni-Kenigsbuch D, Shohat M, Shohat B, Ben-Amitai D, Chan CC, David M (2008) The novel tellurium immunomodulator AS101 inhibits interleukin-10 production and p38 MAPK expression in atopic dermatitis. J Dermatol Sci 50:232–235

    CAS  PubMed  Google Scholar 

  • Suh SJ, Kim KS, Kim MJ et al (2006) Effects of bee venom on protease activities and free radical damages in synovial fluid from type II collagen-induced rheumatoid arthritis rats. Toxicol In Vitro 20:1465–1471

    CAS  PubMed  Google Scholar 

  • Sun M, Wang S, Zhao L et al (2014) Suppression of 2,4-dinitrochlorobenzene-induced atopic dermatitis by extract of Bacillus Calmette–Guerin. Mol Med Rep 9:689–694

    CAS  PubMed  Google Scholar 

  • Sur B, Lee B, Yeom M et al (2016) Bee venom acupuncture alleviates trimellitic anhydride-induced atopic dermatitis-like skin lesions in mice. BMC Complement Altern Med 16:38

    PubMed  PubMed Central  Google Scholar 

  • Suzuki H, Makino Y, Nagata M et al (2016) A rare variant in CYP27A1 and its association with atopic dermatitis with high serum total IgE. Allergy 71:1486–1489

    CAS  PubMed  Google Scholar 

  • Tan HY, Zhang AL, Chen D, Xue CC, Lenon GB (2013) Chinese herbal medicine for atopic dermatitis: a systematic review. J Am Acad Dermatol 69:295–304

    PubMed  Google Scholar 

  • Tanaka A, Konno M, Muto S et al (2005) A novel NF-kappaB inhibitor, IMD-0354, suppresses neoplastic proliferation of human mast cells with constitutively activated c-kit receptors. Blood 105:2324–2331

    CAS  PubMed  Google Scholar 

  • Tanaka A, Muto S, Jung K, Itai A, Matsuda H (2007) Topical application with a new NF-kappaB inhibitor improves atopic dermatitis in NC/NgaTnd mice. J Invest Dermatol 127:855–863

    CAS  PubMed  Google Scholar 

  • Tokura Y (2010) Extrinsic and intrinsic types of atopic dermatitis. J Dermatol Sci 58:1–7

    CAS  PubMed  Google Scholar 

  • Wullaert A, Bonnet MC, Pasparakis M (2011) NF-kappaB in the regulation of epithelial homeostasis and inflammation. Cell Res 21:146–158

    CAS  PubMed  Google Scholar 

  • Yamashita H, Tanaka H, Inagaki N (2013) Treatment of the chronic itch of atopic dermatitis using standard drugs and kampo medicines. Biol Pharm Bull 36:1253–1257

    CAS  PubMed  Google Scholar 

  • Yanashima K, Chieosilapatham P, Yoshimoto E, Okumura K, Ogawa H, Niyonsaba F (2017) Innate defense regulator IDR-1018 activates human mast cells through G protein-, phospholipase C-, MAPK- and NF-kB-sensitive pathways. Immunol Res 65:920–931

    CAS  PubMed  Google Scholar 

  • Yang G, Choi CH, Lee K, Lee M, Ham I, Choi HY (2013) Effects of Catalpa ovata stem bark on atopic dermatitis-like skin lesions in NC/Nga mice. J Ethnopharmacol 145:416–423

    PubMed  Google Scholar 

  • Zhang S, Liu Y, Ye Y et al (2018) Bee venom therapy: potential mechanisms and therapeutic applications. Toxicon 148:64–73

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work is financially supported by the National Research Foundation of Korea [NRF] Grant funded by the Korea Government (MSIP) (Grant number MRC2017R1A5A2015541). We would like to thank Editage (www.editage.co.kr) for English language editing.

Author information

Author notes

  1. YuJin Lee and MyungJin Oh contributed equally to this work.

Authors and Affiliations

  1. College of Pharmacy and Medical Research Center, Chungbuk National University, 194-31 Osongsaengmyeong 1-ro, Osong-eup, Heungduk-gu, Cheongju, Chungbuk, 28160, Republic of Korea

    Yu Jin Lee, Dong Hun Lee, Yong Sun Lee & Jin Tae Hong

  2. College of Oriental Medicine, Gachon University, San 65, Bokjeong-dong, Sujeong-gu, Seongnam, Gyeonggii-do, 461-701, Republic of Korea

    Myung Jin Oh, Jiin Lee, Deok-Hyun Kim, Cheol-Hoon Choi & Ho Sueb Song

  3. Department of Obstetrics and Gynecology, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 64 Daeheung-ro, Jung gu, Daejeon, 301-723, Republic of Korea

    Min Jong Song

Authors
  1. Yu Jin Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Myung Jin Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dong Hun Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yong Sun Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jiin Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Deok-Hyun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Cheol-Hoon Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Min Jong Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ho Sueb Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jin Tae Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ho Sueb Song or Jin Tae Hong.

Ethics declarations

Conflict of interest

The authors declare that there is no duality of interest associated with this manuscript.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, Y.J., Oh, M.J., Lee, D.H. et al. Anti-inflammatory effect of bee venom in phthalic anhydride-induced atopic dermatitis animal model. Inflammopharmacol 28, 253–263 (2020). https://doi.org/10.1007/s10787-019-00646-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10787-019-00646-w

Keywords

Search

Navigation