Anti-inflammatory effects of the ethyl acetate extract of Aquilaria crassna inhibits LPS-induced tumour necrosis factor-alpha production by attenuating P38 MAPK activation
DOI:
https://doi.org/10.22377/ijgp.v5i1.173Abstract
To study the inhibitory effect of the ethyl acetate extract of Aquilaria crassna on lipopolysaccharide (LPS)-induced tumournecrosis factor-alpha (TNF-α) secretion from isolated human peripheral blood mononuclear cells and its mechanisms of antiinflammation so as to provide some evidence for its traditional use. Human peripheral blood mononuclear cells (hPBMCs) were isolated from healthy volunteers. Cells, at a concentration of 1×106 cell/ml, were induced to secrete TNF-α by exposure to 10 ng/ml LPS in the presence and absence of the ethyl acetate extract of Aquilaria crassna. The TNF-α secretion in the collection medium was measured by enzyme-linked immunosorbent assay and the TNF-α gene expression was measured by reverse transcriptase-polymerase chain reaction. Determination of ERK1/2 MAPK and p38 MAPK activation were performedby Western blot analysis using a specific phosphorylated form of ERK1/2, p38 MAPK antibody. LPS at a concentration of 10 ng/ ml significantly increased in TNF-α secretion and was significantly inhibited when treated with 1.5 mg/ml ethyl acetate extract of Aquilaria crassna (P<0.05). Moreover, on treatment with 1.5 mg/ml, the extracts showed TNF-α gene expression inhibition.
Co-treatment of the extract with LPS could not block p38 MAPK activation, but pre-treatment of the extracts significantly
reduced the p38 MAPK phosphorylation without affecting the ERK1/2 MAPK activation (P<0.05). The ethyl acetate extract
of Aquilaria crassna inhibits TNF-α gene expression and secretion in LPS-induced hPBMCs. This inhibitory effect apparently
resulted from selectively attenuating the p38 MAPK activation.
Key words: Anti-inflammatory, Aquilaria crassna, p38 MAPK, PBMCs, TNF-α
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References
Dash M, Patra JK, Panda PP. Phytochemical and antimicrobial
screening of extracts of Aquilaria agallocha Roxb. Afr J Biotechnol
;7:3531-4.
Kim YC, Lee EH, Lee YM, Kim HK, Song BK, Lee EJ, et al. Effect of
the aqueous extract of Aquilaria agallocha stems on the immediate
hypersensitivity reactions. J Ethnopharmacol 1997;58:31-8.
Miniyar PB, Chitre TS, Karve SS, Deuskar HJ, Jain KS. Anti-oxidant
activity of ethyl acetate extract of Aquilaria agallocha on nitriteinduced
methemoglobin formation. Int J Green Pharm 2008;2:
-4.
Gunasekera SP, Kinghorn AD, Cordell GA, Farnsworth NR. Plant
anticancer agents. XIX Constituents of Aquilaria malaccensis. J
Nat Prod 1981;44:569-72.
Okugawa H, Ueda R, Matsumoto K, Kawanishi K, Kato A. Effects
of agarwood extracts on the central nervous system in mice. Planta
Med 1993;59:32-6.
S u v i t a ya va t W, K o d c h a wo n g s J , T h i r a wa r a p a n S S ,
Bunyapraphatsara N. Effects of Ya-hom on the gastric secretion
in rats. J Ethnopharmacol 2004;94:331-8.
Chitre T, Bhutada P, Nandakumar K, Somani R, Miniyar P,
Mundhada Y, et al. Analgesic and anti-inflammatory activity of
heartwood of Aquilaria agallocha in laboratory animals. Pharmacol
Online 2007;1:288-98.
Peana AT, D'aquila PS, Chessa ML, Moretti MD, Serra G, Pippia P.
(-)-Linalool produces antinociception in two experimental models
of pain. Eur J Pharmacol 2003;460:37-41.
Peana AT, D'aquila PS, Panin F, Serra G, Pippia P, Moretti MD. Antiinflammatory
activity of linalool and linalyl acetate constituents
of essential oils. Phytomedicine 2002;9:721-6.
Zhou M, Wang H, Suolangjiba Kou J, Yu B. Antinociceptive and
anti-inflammatory activities of Aquilaria sinensis (Lour.) Gilg.
Leaves extract. J Ethnopharmacol 2008;117:345-50.
Van-Der BT, Nijenhuis S, Van RE, Verhoef J, Van-Asbeck BS.
Lipopolysaccharide-induced tumor necrosis factor alpha
production by human monocytes involves the raf-1/MEK1-MEK2/
ERK1-ERK2 pathway. Infect Immun 1999;67:3824-9.
Bhat NR, Zhang P, Lee JC, Hogan EL. Extracellular signal-regulated
kinase and p38 subgroups of mitogen-activated protein kinases
regulate inducible nitric oxide synthase and tumor necrosis factoralpha
gene expression in endotoxin-stimulated primary glial
cultures. JNeurosci 1998;18:1633-41.
Trotta R, Kanakaraj P, Perussia B. Fc gamma R-dependent mitogenactivated
protein kinase activation in leukocytes: a common signal
transduction event necessary for expression of TNF-alpha and
early activation genes. J Exp Med 1996;184:1027-35.
Hambleton J, Weinstein SL, Lem L, Defranco AL. Activation of
c-Jun N-terminal kinase in bacterial lipopolysaccharide-stimulated
macrophages. Proc Natl Acad Sci USA 1996;93:2774-8.
Han J, Lee JD, Bibbs L, Ulevitch RJ. A MAP kinase targeted by
endotoxin and hyperosmolarity in mammalian cells. Science
;265:808-11.
Sanghera JS, Weinstein SL, Aluwalia M, Girn J, Pelech SL.
Activation of multiple proline-directed kinases by bacterial
lipopolysaccharide in murine macrophages. J Immunol
;156:4457-65.
Lee JC, Young PR. Role of CSB/p38/RK stress response kinase
in LPS and cytokine signaling mechanisms. J Leukoc Biol 1996;
:152-7.
Young PR, Mclaughlin MM, Kumar S, Kassis S, Doyle ML,
Mcnulty D, et al. Pyridinyl imidazole inhibitors of p38 mitogenactivated
protein kinase bind in the ATP site. J Biol Chem 1997;272:
-21.
Swantek JL, Cobb MH, Geppert TD. Jun N-terminal kinase/
stress-activated protein kinase (JNK/SAPK) is required for
lipopolysaccharide stimulation of tumor necrosis factor alpha
(TNF-alpha) translation: glucocorticoids inhibit TNF-alpha
translation by blocking JNK/SAPK. Mol Cell Biol 1997;17:
-82.
Clark JE, Sarafraz N, Marber MS. Potential of p38-MAPK inhibitors
in the treatment of ischaemic heart disease. Pharmacol Ther
;116:192-206.
Kumphune S, Bassi R, Jacquet S, Sicard P, Clark JE, Verma S,
et al. A chemical genetic approach reveals that p38alpha MAPK
activation by diphosphorylation aggravates myocardial infarction
and is prevented by the direct binding of SB203580. J Biol Chem
;285:2968-75.
Suvitayavat W, Tunlert S, Thirawarapan SS, Kitpati C, Bunyapraphatsara
N. Actions of Ya-hom, a herbal drug combination,
on isolated rat aortic ring and atrial contractions. Phytomedicine
;12:561-9.