Browse > Article
http://dx.doi.org/10.1016/j.jgr.2014.11.001

20(S)-Protopanaxatriol inhibits release of inflammatory mediators in immunoglobulin E-mediated mast cell activation  

Kim, Dae Yong (Department of Pharmacology, School of Medicine, Sungkyunkwan University)
Ro, Jai Youl (Department of Pharmacology, School of Medicine, Sungkyunkwan University)
Lee, Chang Ho (Department of Pharmacology, College of Medicine, Hanyang University)
Publication Information
Journal of Ginseng Research / v.39, no.3, 2015 , pp. 189-198 More about this Journal
Abstract
Background: Antiallergic effect of 20(S)-protopanaxatriol (PPT), an intestinal metabolite of ginseng saponins, was investigated in guinea pig lung mast cells and mouse bone marrow-derived mast cells activated by a specific antigen/antibody reaction. Methods: Increasing concentrations of PPT were pretreated 5 min prior to antigen stimulation, and various inflammatory mediator releases and their relevant cellular signaling events were measured in those cells. Results: PPT dose-dependently reduced the release of histamine and leukotrienes in both types of mast cells. Especially, in activated bone marrow-derived mast cells, PPT inhibited the expression of Syk protein, cytokine mRNA, cyclooxygenase-1/2, and phospholipase $A_2$ ($PLA_2$), as well as the activities of various protein kinase C isoforms, mitogen-activated protein kinases, $PLA_2$, and transcription factors (nuclear factor-${\kappa}B$ and activator protein-1). Conclusion: PPT reduces the release of inflammatory mediators via inhibiting multiple cellular signaling pathways comprising the $Ca^{2+}$ influx, protein kinase C, and $PLA_2$, which are propagated by Syk activation upon allergic stimulation of mast cells.
Keywords
20(S)-protopanaxatriol; inflammatory mediators; mast cells; Panax ginseng;
Citations & Related Records
Times Cited By KSCI : 4  (Citation Analysis)
연도 인용수 순위
1 Chang WC, Nelson C, Parekh AB. $Ca^{2+}$ influx through CRAC channels activates cytosolic phospholipase A2, leukotriene C4 secretion, and expression of c-fos through ERK-dependent and -independent pathways in mast cells. FASEB J 2006;20:2381-3.   DOI
2 Kim JY, Kim DY, Ro JY. Granule formation in NGF-cultured mast cells is associated with expressions of pyruvate kinase type M2 and annexin I proteins. Int Arch Allergy Immunol 2008;146:287-97.   DOI
3 Hirasawa N, Santini F, Beaven MA. Activation of the mitogen-activated protein kinase/cytosolic phospholipase A2 pathway in a rat mast cell line. Indications of different pathways for release of arachidonic acid and secretory granules. J Immunol 1995;154:5391-402.
4 Lin X, Takemori H, Katoh Y, Doi J, Horike N, Makino A, Nonaka Y, Okamoto M. Salt-inducible kinase is involved in the ACTH/cAMP-dependent protein kinase signaling in Y1 mouse adrenocortical tumor cells. Mol Endocrinol 2001;15: 1264-76.   DOI
5 Bureau F, Bonizzi G, Kirschvink N, Delhalle S, Desmecht D, Merville MP, Bours V, Lekeux P. Correlation between nuclear factor-kappaB activity in bronchial brushing samples and lung dysfunction in an animal model of asthma. Am J Respir Crit Care Med 2000;161:1314-21.   DOI
6 Choo MK, Park EK, Han MJ, Kim DH. Antiallergic activity of ginseng and its ginsenosides. Planta Med 2003;69:518-22.   DOI
7 Lim YJ, Na HS, Yun YS, Choi IS, Oh JS, Rhee JH, Cho BH, Lee HC. Suppressive effects of ginsan on the development of allergic reaction in murine asthmatic model. Int Arch Allergy Immunol 2009;150:32-42.   DOI
8 Hasegawa H, Sung JH, Matsumiya S, Uchiyama M. Main ginseng saponin metabolites formed by intestinal bacteria. Planta Med 1996;62:453-7.   DOI
9 Bae EA, Park SY, Kim DH. Constitutive beta-glucosidases hydrolyzing ginsenoside Rb1 and Rb2 from human intestinal bacteria. Biol Pharm Bull 2000;23: 1481-5.   DOI
10 Park EK, Choo MK, Kim EJ, Han MJ, Kim DH. Antiallergic activity of ginsenoside Rh2. Biol Pharm Bull 2003;26:1581-4.   DOI
11 Brown JM, Wilson TM, Metcalfe DD. The mast cell and allergic diseases: role in pathogenesis and implications for therapy. Clin Exp Allergy 2008;38:4-18.
12 Kalesnikoff J, Galli SJ. New developments in mast cell biology. Nat Immunol 2008;9:1215-23.   DOI
13 Hakim-Rad K, Metz M, Maurer M. Mast cells: makers and breakers of allergic inflammation. Curr Opin Allergy Clin Immunol 2009;9:427-30.   DOI
14 Okayama Y, Ra C, Saito H. Role of mast cells in airway remodeling. Curr Opin Immunol 2007;19:687-93.   DOI
15 Kim MY, Cho JY. 20S-dihydroprotopanaxadiol, a ginsenoside derivative, boosts innate immune responses of monocytes and macrophages. J Ginseng Res 2013;37:293-9.   DOI
16 Kim MY, Cho JY. 20S-dihydroprotopanaxatriol modulates functional activation of monocytes and macrophages. J Ginseng Res 2013;37:300-7.   DOI
17 Reddy ST, Winstead MV, Tischfield JA, Herschman HR. Analysis of the secretory phospholipase A2 that mediates prostaglandin production in mast cells. J Biol Chem 1997;272:13591-6.   DOI
18 Tanaka O, Nagai M, Shibata S. Chemical studies on the oriental plant drugs. XVI. The stereochemistry of protopanaxadiol, a genuine sapogenin of ginseng. Chem Pharm Bull 1966;14:1150-6.   DOI
19 Ro JY, Lee BC, Kim JY, Chung YJ, Chung MH, Lee SK, Jo TH, Kim KH, Park YI. Inhibitory mechanism of aloe single component (alprogen) on mediator release in guinea pig lung mast cells activated with specific antigen-antibody reactions. J Pharmacol Exp Ther 2000;292:114-21.
20 Kim DY, Park JW, Jeoung D, Ro JY. Celastrol suppresses allergen-induced airway inflammation in a mouse allergic asthma model. Eur J Pharmacol 2009;612:98-105.   DOI
21 Takata M, Sabe H, Hata A, Inazu T, Homma Y, Nukada T, Yamamura H, Kurosaki T. Tyrosine kinases Lyn and Syk regulate B cell receptor-coupled $Ca^{2+}$ mobilization through distinct pathways. EMBO J 1994;13:1341-9.
22 Barbu EA, Zhang J, Siraganian RP. The limited contribution of Fyn and Gab2 to the high affinity IgE receptor signaling in mast cells. J Biol Chem 2010;285: 15761-8.   DOI
23 Fehrenbach K, Lessmann E, Zorn CN, Kuhny M, Grochowy G, Krystal G, Leitges M, Huber M. Steel factor enhances supraoptimal antigen-induced IL-6 production from mast cells via activation of protein kinase C-beta. J Immunol 2009;182:7897-905.   DOI
24 Boyce JA. Eicosanoid mediators of mast cells: receptors, regulation of synthesis, and pathobiologic implications. Chem Immunol Allergy 2005;87:59-79.
25 Lin TY, London CA. Characterization and modulation of canine mast cell derived eicosanoids. Vet Immunol Immunopathol 2010;135:118-27.   DOI
26 Turner H, Kinet JP. Signalling through the high-affinity IgE receptor Fc epsilonRI. Nature 1999;402:B24-30.   DOI
27 Marshall JS, Jawdat DM. Mast cells in innate immunity. J Allergy Clin Immunol 2004;114:21-7.   DOI
28 Ichikawa H, Takada Y, Shishodia S, Jayaprakasam B, Nair MG, Aggarwal BB. Withanolides potentiate apoptosis, inhibit invasion, and abolish osteoclastogenesis through suppression of nuclear factor-kappaB (NF-kappaB) activation and NF-kappaB-regulated gene expression. Mol Cancer Ther 2006;5: 1434-45.   DOI
29 Kimata M, Shichijo M, Miura T, Serizawa I, Inagaki N, Nagai H. $Ca^{2+}$ and protein kinase C signaling for histamine and sulfidoleukotrienes released from human cultured mast cells. Biochem Biophys Res Commun 1999;257: 895-900.   DOI
30 Triggiani M, Granata F, Frattini A, Marone G. Activation of human inflammatory cells by secreted phospholipases A2. Biochim Biophys Acta 2006;1761: 1289-300.   DOI
31 Leslie CC. Properties and regulation of cytosolic phospholipase A2. J Biol Chem 1997;272:16709-12.   DOI
32 Lee YN, Tuckerman J, Nechushtan H, Schutz G, Razin E, Angel P. c-Fos as a regulator of degranulation and cytokine production in FcepsilonRI-activated mast cells. J Immunol 2004;173:2571-7.   DOI
33 Kettner A, Di Matteo M, Santoni A. Insulin potentiates FcepsilonRI-mediated signaling in mouse bone marrow-derived mast cells. Mol Immunol 2010;47: 1039-46.   DOI
34 Kempuraj D, Huang M, Kandere-Grzybowska K, Basu S, Boucher W, Letourneau R, Athanassiou A, Theoharides TC. Azelastine inhibits secretion of IL-6, TNF-alpha and IL-8 as well as NF-kappaB activation and intracellular calcium ion levels in normal human mast cells. Int Arch Allergy Immunol 2003;132:231-9.   DOI
35 Liu J, Wang S, Liu H, Yang L, Nan G. Stimulatory effect of saponin from Panax ginseng on immune function of lymphocytes in the elderly. Mech Ageing Dev 1995;83:43-53.   DOI
36 Macian FNFAT. proteins: key regulators of T-cell development and function. Nat Rev Immunol 2005;5:472-84.   DOI
37 Klein M, Klein-Hessling S, Palmetshofer A, Serfling E, Tertilt C, Bopp T, Heib V, Becker M, Taube C, Schild H, et al. Specific and redundant roles for NFAT transcription factors in the expression of mast cell-derived cytokines. J Immunol 2006;177:6667-74.   DOI
38 Perkins ND. Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol 2007;8:49-62.   DOI
39 Kang S, Min H. Ginseng, the 'immunity boost': the effects of Panax ginseng on immune system. J Ginseng Res 2012;36:354-68.   DOI
40 Mizuno M, Yamada J, Terai H, Kozukue N, Lee YS, Tsuchida H. Differences in immunomodulating effects between wild and cultured Panax ginseng. Biochem Biophys Res Commun 1994;200:1672-8.   DOI
41 Park EK, Choo MK, Han MJ, Kim DH. Ginsenoside Rh1 possesses antiallergic and anti-inflammatory activities. Int Arch Allergy Immunol 2004;133:113-20.   DOI
42 Scaglione F, Ferrara F, Dugnani S, Falchi M, Santoro G, Fraschini F. Immunomodulatory effects of two extracts of Panax ginseng C.A. Meyer. Drugs Exp Clin Res 1990;16:537-42.
43 Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol 1999;58:1685-93.   DOI
44 Hu S, Concha C, Cooray R, Holmberg O. Ginseng-enhanced oxidative and phagocytic activities of polymorphonuclear leucocytes from bovine peripheral blood and stripping milk. Vet Res 1995;26:155-61.
45 Kim KM, Kwon HS, Jeon SG, Park CH, Sohn SW, Kim DI, Kim SS, Chang YS, Kim YK, Cho SH, et al. Korean ginseng-induced occupational asthma and determination of IgE binding components. J Korean Med Sci 2008;23:232-5.   DOI
46 Ro JY, Ahn YS, Kim KH. Inhibitory effect of ginsenoside on the mediator release in the guinea pig lung mast cells activated by specific antigen-antibody reactions. Int J Immunopharmacol 1998;20:625-41.   DOI
47 Babayigit A, Olmez D, Karaman O, Bagriyanik HA, Yilmaz O, Kivcak B, Erbil G, Uzuner N. Ginseng ameliorates chronic histopathologic changes in a murine model of asthma. Allergy Asthma Proc 2008;29:493-8.   DOI
48 Song JY, Han SK, Son EH, Pyo SN, Yun YS, Yi SY. Induction of secretory and tumoricidal activities in peritoneal macrophages by ginsan. Int Immunopharmacol 2002;2:857-65.   DOI
49 Ahn JY, Song JY, Yun YS, Jeong G, Choi IS. Protection of Staphylococcus aureusinfected septic mice by suppression of early acute inflammation and enhanced antimicrobial activity by ginsan. FEMS Immunol Med Microbiol 2006;46:187-97.   DOI