Abstract:
BACKGROUND AND PURPOSE:Betulinic acid (BA) is a naturally occurring triterpenoid widely distributed throughout the plant kingdom. We previously reported that BA inhibits lipopolysaccharide (LPS)-induced interleukin-6 production through modulation of nuclear factor κB (NF-κB) in human peripheral blood mononuclear cells (hPBMCs). This study attempted to identify other mechanisms through which BA modulates LPS signalling in mononuclear cells. The effects of BA on signalling pathways downstream were focused on in this study. EXPERIMENTAL APPROACH:We determined the ability of BA to interfere with p38 and extracellular regulated kinase (ERK) phosphorylation as well as Akt phosphorylation and nuclear factor-κB activation using LPS-activated hPBMCs as an in vitro model. LPS-induced endotoxin shock in mice was the in vivo model employed. KEY RESULTS:BA inhibited LPS-induced COX-2 protein expression and prostaglandin E(2) production and also attenuated LPS-induced ERK and Akt phosphorylation, but not p38 in hPBMCs. BA abolished LPS-induced IκBα phosphorylation and thus normalized the levels of IκBα in cytosol. BA also inhibited LPS-induced reactive oxygen species formation and lactate dehydrogenase release. Interestingly, BA improved the life span of mice in endotoxin shock and also inhibited PGE(2) production and myeloperoxidase activity in vivo. CONCLUSIONS AND IMPLICATIONS:BA modulates LPS-induced COX-2 expression in hPBMCs by inhibiting ERK and Akt pathways as well as by modulating IκBα phosphorylation. At the same time, no cell toxicity was observed. The effect of the drug was confirmed through in vivo experiments. The study gives an insight into the molecular mechanisms of BA.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Viji V,Helen A,Luxmi VRdoi
10.1111/j.1476-5381.2010.01112.xsubject
Has Abstractpub_date
2011-03-01 00:00:00pages
1291-303issue
6eissn
0007-1188issn
1476-5381journal_volume
162pub_type
杂志文章abstract::1. Bicyclic compounds with potential thymoleptic properties (Lu-compounds) have recently become available, and their effects on the membrane pumps of the central and peripheral monoamine neurones have now been tested and compared with those of the tricyclic antidepressant drugs.2. Biochemical and histochemical in vivo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb08299.x
更新日期:1969-05-01 00:00:00
abstract::1. The effects of seven agonist and three antagonist adenosine receptor ligands were compared on the guinea-pig sinoatrial (SA) node (isolated right atrium) and atrioventricular (AV) node (perfused whole heart). Single agonist concentration-effect curves were obtained to 5'-N-ethylcarboxamidoadenosine (NECA), R(-)-N6-...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701891
更新日期:1998-06-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703274
更新日期:2000-04-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13531
更新日期:2016-09-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703492
更新日期:2000-08-01 00:00:00
abstract::1 Embryonic sensory neurones of the chick grown in dissociated cell culture respond to application of low concentrations of gamma-aminobutyric acid (GABA) with a change in resting membrane resistance (R(in)) and/or a change in action potential duration (APD) (Dunlap & Fischbach, 1978; Choi & Fischbach, 1981). Intracel...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1981.tb10467.x
更新日期:1981-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Gallium (Ga) has been shown to be effective in the treatment of disorders associated with accelerated bone loss, including cancer-related hypercalcemia and Paget's disease. These clinical applications suggest that Ga could reduce bone resorption. However, few studies have studied the effects of G...
journal_title:British journal of pharmacology
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更新日期:2010-04-01 00:00:00
abstract::1. The uptake and release of (3)H-digitoxigenin by electrically driven, guinea-pig isolated atria (frequency 180/min) has been determined for two different medium concentrations of the genin. Both concentrations-1 x 10(-7) and 5 x 10(-7) g/ml.-caused a pronounced increase in contractile force.2. The uptake of (3)H-dig...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1968.tb08490.x
更新日期:1968-11-01 00:00:00
abstract::1. The novel bradykinin antagonist, HOE 140, completely blocked the fall in rabbit blood pressure caused, not only by i.v. bradykinin, but also by i.v. kallikrein. This shows that both the effects of exogenously administered bradykinin and those of endogenously released kinins are antagonized by HOE 140. 2. Acute panc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb12751.x
更新日期:1992-10-01 00:00:00
abstract::1. The fall in arterial blood pressure with bradycardia that occurs on injection of clonidine into the cerebral ventricles and into the cisterna magna is attributed to an action on ;chemosensitive zones' situated at the ventral surface of the brain stem. This conclusion is based on the following results obtained in ca...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08532.x
更新日期:1973-12-01 00:00:00
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pub_type: 杂志文章
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更新日期:2010-09-01 00:00:00
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0705062
更新日期:2003-02-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13702.x
更新日期:1993-08-01 00:00:00
abstract::1. In order to determine whether activation of adenosine triphosphate (ATP)-sensitive K+ channels exclusively explains the hypoxia- and ischaemia-induced action potential shortening, effects of tolbutamide and glibenclamide on changes in action potential duration (APD) during hypoxia, metabolic blockade or experimenta...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12294.x
更新日期:1991-05-01 00:00:00
abstract::1 Rats treated for seven days with seryl-trihydroxybenzylhydrazine (benserazide), and inhibitor of peripheral aromatic L-amino acid decarboxylase (500 mg/kg, daily, i.p.) alone or in combination with L-DOPA methylester (500 mg/kg, daily, i.p.) for seven days showed a moderate but significant decrease of liver aldehyde...
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb16746.x
更新日期:1977-05-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1986.tb11122.x
更新日期:1986-09-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11470.x
更新日期:1988-04-01 00:00:00
abstract::1. Protection against 1-methyl-4-phenylpyridinium ion (MPP+) neurotoxicity by two nitric oxide-related compounds, N omega-nitro-L-arginine (L-NOARG) and L-arginine, was studied in the corpus striatum by means of two MPP+ perfusions separated by 24 h. Dopamine extracellular output after the second MPP+ (1, 5 and 10 mM)...
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb14814.x
更新日期:1994-03-01 00:00:00
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pub_type: 杂志文章
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更新日期:2009-06-01 00:00:00
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更新日期:2002-08-01 00:00:00
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pub_type: 评论,杂志文章,评审
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更新日期:2007-12-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12448.x
更新日期:1991-10-01 00:00:00
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pub_type: 杂志文章
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更新日期:1996-12-01 00:00:00
abstract::1. The affinity of the alpha 1-adrenoceptor antagonist SB 216469 (also known as REC 15/2739) has been determined at native and cloned alpha 1-adrenoceptor subtypes by radioligand binding and at functional alpha 1-adrenoceptor subtypes in isolated tissues. 2. In radioligand binding studies with [3H]-prazosin, SB 216469...
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pub_type: 杂志文章
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更新日期:1996-11-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:1987-11-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:2015-04-01 00:00:00
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pub_type: 杂志文章
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更新日期:1995-10-01 00:00:00
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pub_type: 杂志文章
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更新日期:2003-01-01 00:00:00