Suppression of inflammatory response and endothelial nitric oxide synthase downregulation in hyperlipidaemic C57BL/6J mice by eugenosedin-A

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Title:	Suppression of inflammatory response and endothelial nitric oxide synthase downregulation in hyperlipidaemic C57BL/6J mice by eugenosedin-A
Authors:	Shen KP;Lin HL;Chang WT;An LM;Chen IJ;Wu BN
Date:	2011-06
Issue Date:	2011-09-30T07:36:07Z (UTC)
Abstract:	OBJECTIVES: Eugenosedin-A has been found to ameliorate high-fat diet (HFD)-induced hyperglycaemia and hyperlipidaemia in C57BL/6J mice. This study aimed to investigate the mechanisms of action of eugenosedin-A on endothelial function and inflammation in hyperlipidaemic mice. METHODS: C57BL/6J mice were randomly divided into two control groups and two treatment groups. The control mice received either a regular diet or HFD, and the treatment groups were fed HFD with either 5 mg/kg eugenosedin-A or atorvastatin for eight weeks. KEY FINDINGS: Mice fed a HFD had higher concentrations of nitrate (NO) but not prostaglandin E2 (PGE2), increased tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) mRNA and inducible nitric oxide synthase (iNOS) proteins, but decreased endothelial nitric oxide synthase (eNOS) proteins. HFD-induced upregulation of iNOS is associated with p38, extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK), PI3K and Akt/IKKα/p65. Eugenosedin-A and atorvastatin reduced HFD-induced TNF-α and IFN-γ mRNA, NO generation, upregulation of iNOS protein, and down-regulation of eNOS protein. Both agents inhibited p38, ERK, JNK and Akt/IKKα/p65 protein levels in the aorta. However, eugenosedin-A did not significantly reduce p38 in the liver. CONCLUSIONS: Our results showed an association between obesity-induced inflammation and altered levels of TNF-α, IFN-γ, p38, ERK, JNK and Akt/IKKα/p65. Eugenosedin-A, like atorvastatin, could inhibit p38, ERK, JNK, Akt/IKKα/p65 proteins, as well as TNF-α and IFN-γ mRNA during the regulation of the obesity-induced inflammatory process.
Relation:	J Pharm Pharmacol. 2011 Jun;63(6):860-8
Appears in Collections:	[Department of Nursing] Papers

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