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

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2017

Open Access 01-12-2017 | Research article

Tonggyu-tang, a traditional Korean medicine, suppresses pro-inflammatory cytokine production through inhibition of MAPK and NF-κB activation in human mast cells and keratinocytes

Authors: Hyo In Kim, Se Hyang Hong, Jin Mo Ku, Sooyeon Kang, Tai Young Kim, Yong Cheol Shin, Seong-Gyu Ko

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

Login to get access

Abstract

Background

Allergic diseases including allergic rhinitis, asthma, and atopic dermatitis are increasing worldwide. Common medications used to treat these inflammatory disorders are anti-histamines and corticosteroids, but they have their own limitations such as short duration and severe side effects. Thus, interest in complementary and alternative medicine is continually growing. Here, we investigate the anti-inflammatory mechanisms of Tonggyu-tang (TGT), a traditional Korean medicine that has been used to treat patients with allergic nasal disorders.

Methods

We measured mRNA expressions and production of pro-inflammatory cytokines such as interleukin (IL)-4, IL-6, IL-8 and tumor necrosis factor alpha (TNF-α) by RT-PCR and ELISA assays in HMC-1 (human mast cell line-1) and HaCaT cells, immortalized human keratinocytes. Moreover, we evaluated the effect of TGT on two major inflammation-related pathways, mitogen activated protein kinase (MAPK) and NF-κB signaling pathway in these two cells.

Results

Our results revealed that that TGT significantly reduced the expression and production of inflammatory cytokines such as IL-4, IL-6, IL-8, and TNF-α in the agonist-treated HMC-1 and HaCaT cells. We also found that TGT suppressed MAPK signaling pathway including extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38), and c-Jun N-terminal kinase (JNK) as well as NF-κB pathway, which are known to regulate inflammatory cytokine expression.

Conclusion

Taken together, our results demonstrate that TGT inhibits expression of pro-inflammatory cytokines by suppressing MAPK and NF-kB pathway in both mast cells and keratinocytes, suggesting the potential use of TGT in treating allergic inflammatory diseases.
Appendix
Available only for authorised users
Literature
1.
Bradding P, Feather IH, Wilson S, Bardin PG, Heusser CH, Holgate ST, et al. Immunolocalization of cytokines in the nasal mucosa of normal and perennial rhinitic subjects. The mast cell as a source of IL-4, IL-5, and IL-6 in human allergic mucosal inflammation. J Immunol. 1993;151(7):3853–65.PubMed
2.
Minty A, Chalon P, Derocq JM, Dumont X, Guillemot JC, Kaghad M, et al. Interleukin-13 is a new human lymphokine regulating inflammatory and immune responses. Nature. 1993;362(6417):248–50.CrossRefPubMed
3.
Hammad H, Lambrecht BN. Dendritic cells and epithelial cells: linking innate and adaptive immunity in asthma. Nat Rev Immunol. 2008;8(3):193–204.CrossRefPubMed
4.
Holgate ST, Polosa R. Treatment strategies for allergy and asthma. Nat Rev Immunol. 2008;8(3):218–30.CrossRefPubMed
5.
Hoyte FC, Katial RK. Antihistamine therapy in allergic rhinitis. Immunol Allergy Clin N Am. 2011;31(3):509–43.CrossRef
6.
Hajar T, Leshem YA, Hanifin JM, Nedorost ST, Lio PA, Paller AS, et al. A systematic review of topical corticosteroid withdrawal ("steroid addiction") in patients with atopic dermatitis and other dermatoses. J Am Acad Dermatol. 2015;72(3):541–9. e2CrossRefPubMed
7.
Oh HA, Kim HM, Jeong HJ. Alleviation of allergic rhinitis symptoms with Pyeongwee-san extract (KMP6). Immunopharmacol Immunotoxicol. 2012;34(1):135–42.CrossRefPubMed
8.
Jeong KT, Kim SG, Lee J, Park YN, Park HH, Park NY, et al. Anti-allergic effect of a Korean traditional medicine, Biyeom-tang on mast cells and allergic rhinitis. BMC Complement Altern Med. 2014;14:54.CrossRefPubMedPubMedCentral
9.
Hong SH, Kim SR, Choi HS, Ku JM, Seo HS, Shin YC, et al. Effects of Hyeonggaeyeongyo-tang in ovalbumin-induced allergic rhinitis model. Mediat Inflamm. 2014;2014:418705.CrossRef
10.
Ku JM, Hong SH, Kim SR, Choi HS, Seo HS, Jang BH, et al. Anti-allergic effects of so-Cheong-Ryong-tang in ovalbumin-induced allergic rhinitis model. Eur Arch Otorhinolaryngol. 2016;273(1):123–31.CrossRefPubMed
11.
Lee K-J, Nam H-J, Kim Y-B. Effect of Tongqiao-tang on OVA induced allergic rhinitis mouse model. The Journal of Korean Oriental Medicine. 2008;29(5):96–103.
12.
Ryu M, Kim EH, Chun M, Kang S, Shim B, Yu YB, et al. Astragali radix elicits anti-inflammation via activation of MKP-1, concomitant with attenuation of p38 and Erk. J Ethnopharmacol. 2008;115(2):184–93.CrossRefPubMed
13.
Qin Q, Niu J, Wang Z, Xu W, Qiao Z, Gu Y. Astragalus Membranaceus inhibits inflammation via phospho-P38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappaB pathways in advanced glycation end product-stimulated macrophages. Int J Mol Sci. 2012;13(7):8379–87.CrossRefPubMedPubMedCentral
14.
Yeom M, Kim JH, Min JH, Hwang MK, Jung HS, Sohn Y. Xanthii fructus inhibits inflammatory responses in LPS-stimulated RAW 264.7 macrophages through suppressing NF-kappaB and JNK/p38 MAPK. J Ethnopharmacol. 2015;176:394–401.CrossRefPubMed
15.
Kim D-Y, Jeong W-S, Moon H-C, Park S-J. Water extract of flowers of Magnolia denudata inhibits LPS-induced nitric oxide and pro-inflammatory cytokines production in Murine peritoneal macrophage by inhibiting NF-{\kappa}B activation. Korean Journal of Oriental Physiology and Pathology. 2007;21(4):916–20.
16.
Verma SM, Arora H, Dubey R. Anti - inflammatory and sedative - hypnotic activity of the methanolic extract of the leaves of Mentha arvensis. Anc Sci Life. 2003;23(2):95–9.PubMedPubMedCentral
17.
Kyriakis JM, Avruch J. Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update. Physiol Rev. 2012;92(2):689–737.CrossRefPubMed
18.
Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, et al. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev. 2001;22(2):153–83.PubMed
19.
Finco TS, Baldwin AS. Mechanistic aspects of NF-kappa B regulation: the emerging role of phosphorylation and proteolysis. Immunity. 1995;3(3):263–72.CrossRefPubMed
20.
Barnes PJ, Karin M. Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med. 1997;336(15):1066–71.CrossRefPubMed
21.
Zheng T, Yu J, Oh MH, Zhu Z. The atopic march: progression from atopic dermatitis to allergic rhinitis and asthma. Allergy Asthma Immunol Res. 2011;3(2):67–73.CrossRefPubMedPubMedCentral
22.
Kim H, Bae S, Kwon KY, Hwang YI, Kang JS, Lee WJ. A combinational effect of acetaminophen and oriental herbs on the regulation of inflammatory mediators in microglia cell line, BV2. Anat Cell Biol. 2015;48(4):244–50.CrossRefPubMedPubMedCentral
23.
Min SW, Park YJ, Kim DH. Kakkalide and its metabolite irisolidone ameliorate carrageenan-induced inflammation in mice by inhibiting NF-kappaB pathway. Inflammation. 2011;34(5):344–51.CrossRefPubMed
24.
Lee YJ, Hwang SM, Yoon JJ, Lee SM, Kyung EH, Kim JS, et al. Inhibitory effect of Thuja orientalis on TNF-alpha-induced vascular inflammation. Phytother Res. 2010;24(10):1489–95.CrossRefPubMed
25.
Jung HW, Kang SY, Park KH, Oh TW, Jung JK, Kim SH, et al. Effect of the semen extract of Thuja orientalis on inflammatory responses in transient focal cerebral ischemia rat model and LPS-stimulated BV-2 microglia. Am J Chin Med. 2013;41(1):99–117.CrossRefPubMed
26.
Shin IS, Shin NR, Jeon CM, Kwon OK, Hong JM, Kim HS, et al. Thuja orientalis Reduces airway inflammation in ovalbumin-induced allergic asthma. Mol Med Rep. 2015;12(3):4640–6.PubMed
27.
Yeom GG, Min S, Kim SY. 2,3,5,6-Tetramethylpyrazine of Ephedra sinica regulates melanogenesis and inflammation in a UVA-induced melanoma/keratinocytes co-culture system. Int Immunopharmacol. 2014;18(2):262–9.CrossRefPubMed
28.
Wang Q, Shu Z, Xing N, Xu B, Wang C, Sun G, et al. A pure polysaccharide from Ephedra sinica treating on arthritis and inhibiting cytokines expression. Int J Biol Macromol. 2016;86:177–88.CrossRefPubMed
29.
Cao LH, Lee YJ, Kang DG, Kim JS, Lee HS. Effect of Zanthoxylum schinifolium on TNF-alpha-induced vascular inflammation in human umbilical vein endothelial cells. Vasc Pharmacol. 2009;50(5–6):200–7.CrossRef
30.
Quang TH, Ngan NT, Minh CV, Kiem PV, Tai BH, Thao NP, et al. Anti-inflammatory and PPAR transactivational effects of secondary metabolites from the roots of Asarum Sieboldii. Bioorg Med Chem Lett. 2012;22(7):2527–33.CrossRefPubMed
31.
Ram A, Mabalirajan U, Das M, Bhattacharya I, Dinda AK, Gangal SV, et al. Glycyrrhizin alleviates experimental allergic asthma in mice. Int Immunopharmacol. 2006;6(9):1468–77.CrossRefPubMed
32.
Genovese T, Menegazzi M, Mazzon E, Crisafulli C, Di Paola R, Dal Bosco M, et al. Glycyrrhizin reduces secondary inflammatory process after spinal cord compression injury in mice. Shock. 2009;31(4):367–75.CrossRefPubMed
33.
Chu X, Ci X, Wei M, Yang X, Cao Q, Guan M, et al. Licochalcone a inhibits lipopolysaccharide-induced inflammatory response in vitro and in vivo. J Agric Food Chem. 2012;60(15):3947–54.CrossRefPubMed
34.
Li C, Eom T, Jeong Y. Glycyrrhiza glabra L. Extract inhibits LPS-induced inflammation in RAW macrophages. J Nutr Sci Vitaminol (Tokyo) 2015, 61(5):375-381.
35.
Gonzalez-Reyes S, Santillan-Cigales JJ, Jimenez-Osorio AS, Pedraza-Chaverri J, Guevara-Guzman R. Glycyrrhizin ameliorates oxidative stress and inflammation in hippocampus and olfactory bulb in lithium/pilocarpine-induced status epilepticus in rats. Epilepsy Res. 2016;126:126–33.CrossRefPubMed
36.
Zhang WJ, Hufnagl P, Binder BR, Wojta J. Antiinflammatory activity of astragaloside IV is mediated by inhibition of NF-kappaB activation and adhesion molecule expression. Thromb Haemost. 2003;90(5):904–14.PubMed
37.
Chu XP, Xu ZH, Zhan GX, Wu DZ, Qiu MF, Jia W. Study on the proportion & mechanism of reliving asthma of drug partnership comprising herbal Ephedrae sinica & Pheretima aspergilum. Zhongguo Zhong Yao Za Zhi. 2006;31(3):236–9.PubMed
38.
Kim SJ, Gao Zhang C, Taek LJ. Mechanism of anti-nociceptive effects of Asarum Sieboldii Miq. Radix: potential role of bradykinin, histamine and opioid receptor-mediated pathways. J Ethnopharmacol. 2003;88(1):5–9.CrossRefPubMed
39.
Luo GJ, Gan XL, Hei ZQ, Chen LX, Li SR. Effect of Astragalus membranacaus injection on activity of intestinal mucosal mast cells and inflammatory response after hemorrahagic shock-reperfusion in rats. Zhongguo Zhong Yao Za Zhi. 2007;32(14):1436–40.PubMed
40.
Hong SH, Oh MJ, Lee EJ, Park JH, Kim NH, Rhee HK, et al. Processed Xanthii fructus increases cell viability of mast cell line, RBL-2H3. Orient Pharm Exp Med. 2004;4(1):60–4.CrossRef
41.
Shen Y, Pang EC, Xue CC, Zhao ZZ, Lin JG, Li CG. Inhibitions of mast cell-derived histamine release by different Flos Magnoliae species in rat peritoneal mast cells. Phytomedicine. 2008;15(10):808–14.CrossRefPubMed
42.
Shin TY. Inhibition of immunologic and nonimmunologic stimulation-mediated anaphylactic reactions by the aqueous extract of Mentha arvensis. Immunopharmacol Immunotoxicol. 2003;25(2):273–83.CrossRefPubMed
43.
Stassen M, Muller C, Arnold M, Hultner L, Klein-Hessling S, Neudorfl C, et al. IL-9 and IL-13 production by activated mast cells is strongly enhanced in the presence of lipopolysaccharide: NF-kappa B is decisively involved in the expression of IL-9. J Immunol. 2001;166(7):4391–8.CrossRefPubMed
44.
Barnes PJ, Adcock I. Anti-inflammatory actions of steroids: molecular mechanisms. Trends Pharmacol Sci. 1993;14(12):436–41.CrossRefPubMed
45.
Ershler WB, Keller ET. Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty. Annu Rev Med. 2000;51:245–70.CrossRefPubMed
46.
Wedi B, Raap U, Lewrick H, Kapp A. IL-4-induced apoptosis in peripheral blood eosinophils. J Allergy Clin Immunol. 1998;102(6 Pt 1):1013–20.CrossRefPubMed
47.
Levi-Schaffer F, Temkin V, Malamud V, Feld S, Zilberman Y. Mast cells enhance eosinophil survival in vitro: role of TNF-alpha and granulocyte-macrophage colony-stimulating factor. J Immunol. 1998;160(11):5554–62.PubMed
48.
Zheng T, Oh MH, Oh SY, Schroeder JT, Glick AB, Zhu Z. Transgenic expression of interleukin-13 in the skin induces a pruritic dermatitis and skin remodeling. J Invest Dermatol. 2009;129(3):742–51.CrossRefPubMed
Metadata
Title
Tonggyu-tang, a traditional Korean medicine, suppresses pro-inflammatory cytokine production through inhibition of MAPK and NF-κB activation in human mast cells and keratinocytes
Authors
Hyo In Kim
Se Hyang Hong
Jin Mo Ku
Sooyeon Kang
Tai Young Kim
Yong Cheol Shin
Seong-Gyu Ko
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-017-1704-5

Other articles of this Issue 1/2017

BMC Complementary Medicine and Therapies 1/2017 Go to the issue

Research article

Chemical composition and evaluation of the antibacterial and Cytotoxic activities of the essential oil from the leaves of Myracrodruon urundeuva

Research article

Post-market outcome of an extract of traditional Cretan herbs on upper respiratory tract infections: a pragmatic, prospective observational study

Research article

The modified Yi qi decoction protects cardiac ischemia-reperfusion induced injury in rats

Research article

Profile of bioactive compounds in Nymphaea alba L. leaves growing in Egypt: hepatoprotective, antioxidant and anti-inflammatory activity

Research article

Influence of Plantago ovata husk (dietary fiber) on the bioavailability and other pharmacokinetic parameters of metformin in diabetic rabbits

Research article

Ameliorative potential of Alstonia scholaris (Linn.) R. Br. against chronic constriction injury-induced neuropathic pain in rats