자주쓴풀 메탄올추출물의 IgE-매개 알레르기 반응 억제 및 기전 = Swertia pseudochinensis Methanol Extract Inhibits IgE-mediated Allergic Response In vitro and In vivo

다국어 초록 (Multilingual Abstract)

Mast cells play a key role in IgE-mediated allergic response. We investigated whether Swertia pseudochinensis Hara extract (SPE) inhibits IgE-mediated allergic response in mast cells and an allergic animal model. Additionally, we explored SPE’s mechanism of action in mast cells. Our results showed that SPE inhibited both antigen-stimulated degranulation and the production of TNF-a and IL-4 in bone marrow-derived mast cells (BMMCs) and rat basophilic leukemia (RBL)-2H3 cells. SPE also suppressed allergic response in IgE-mediated passive cutaneous anaphylaxis (PCA) in mice. As for the mechanism of action of SPE in mast cells, it inhibited the activation of Syk kinase, a critical signaling protein in the FcεRI-mediated signaling pathway, and also the activation of LAT, a downstream adaptor protein of Syk. We further observed the reduced activation of mitogen-activated protein (MAP) kinases (P38, ERK1/2, and JNK) and Akt in mast cells. Our results described for the first time that SPE has an anti-allergic effect by suppressing mast cells through the inhibition of Syk kinase. Therefore, SPE may be useful for the treatment of type I allergic diseases.

참고문헌 (Reference)

1 김희규, "알레르기 염증에서의 비만세포 역할과 비만세포 관련 질환" 대한 소아알레르기 호흡기학회 5 (5): 248-255, 2017

2 생약학교재편찬위원회, "생약학" 동명사 177-178, 2001

3 정유진, "급·만성 기관지염과 알레르기성 비염의 국내 의료 이용 현황 분석" 대한한의학회 40 (40): 87-98, 2019

4 Yang, S., "Transcriptional regulation by the MAP kinase signaling cascades" 320 : 3-21, 2003

5 Helm, B., "The mast cell binding site on human immunoglobulin E" 331 : 180-183, 1988

6 Theoharides, T. C., "The critical role of mast cells in allergy and inflammation" 1088 : 78-99, 2006

7 Reber, L. L., "Targeting mast cells in inflammatory diseases" 142 : 416-435, 2014

8 Yang, Q., "Sweroside ameliorates NAFLD in high-fat diet induced obese mice through the regulation of lipid metabolism and inflammatory response" 255 : 112556-, 2020

9 Tkaczyk, C., "Roles of adaptor molecules in mast cell activation" 43-58, 2005

10 Hoyte, F, "Recent advances in allergic rhinitis" 7 : 2018

11 Li, Y. L., "RP-HPLC determination and pharmacokinetic study of magniferin in rat plasma after taking traditional Chinese medicinal-preparation : Zhimu decoction" 57 : 767-770, 2003

12 Sheng, N., "Pharmacokinetic and excretion study of three secoiridoid glycosidesand three flavonoid glycosides in rat by LC–MS/MS after oraladministration of the Swertia pseudochinensis extract" 967 : 75-83, 2014

13 Beaven, M. A., "Our perception of the mast cell from Paul Ehrlich to now" 39 : 11-25, 2009

14 Rivera, J., "Molecular regulation of mast cell activation" 117 : 1214-1223, 2006

15 Bradding, P., "Mast cells in asthma-state of the art" 46 : 194-263, 2016

16 Li, Y. L., "LC determination and pharmacokinetic study of mangiferin in rat plasma and tissues" 67 : 957-960, 2008

17 Lin, C. M., "Isovitexin suppresses lipopolysaccharide-mediated inducible nitric oxide synthase through inhibition of NF-kappa B in mouse macrophages" 71 : 748-753,

18 Azzolina, A., "Involvement of p38 and JNK MAPKs pathways in Substance Pinduced production of TNF-alpha by peritoneal mast cells" 18 : 72-80, 2002

19 Galli, S. J., "IgE and mast cells in allergic disease" 18 : 693-704, 2012

20 Tanaka T., "Flavonoids for allergic diseases: present evidence and future perspective" 20 : 879-885, 2014

21 Eiseman, "Engagement of the highaffinity IgE receptor activates src protein-related tyrosine kinases" 355 : 78-80, 1992

22 Kumarasamy, Y., "Bioactivity of secoiridoid glycosides from Centaurium Erythraea" 10 : 344-347, 2003

23 Yamahara, J., "Anticholinergic action of Swertia japonica and an active constituent" 33 : 31-35, 1991

24 박윤형, "A 9-year Trend in the Prevalence of Allergic Disease Based on National Health Insurance Data" 대한예방의학회 48 (48): 301-309, 2015