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

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.

• Authors: Kuo-Ping Shen, Hui-Li Lin, Wen-Tsan Chang, Li-Mei An, Ing-Jun Chen, Bin-Nan Wu
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 63 Issue 6 Pg. 860-8 (Jun 2011) ISSN: 2042-7158 [Electronic] England
• PMID: 21585385 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

Chemical References

• Anti-Inflammatory Agents
• Dietary Fats
• Heptanoic Acids
• Piperazines
• Pyrroles
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• eugenosedin-A
• Nitric Oxide
• Interferon-gamma
• Atorvastatin
• Nitric Oxide Synthase Type III
• Mitogen-Activated Protein Kinases

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Aorta (drug effects, metabolism)
• Atorvastatin
• Dietary Fats (adverse effects)
• Down-Regulation
• Endothelium, Vascular (drug effects, metabolism)
• Female
• Heptanoic Acids (pharmacology, therapeutic use)
• Hyperlipidemias (chemically induced, drug therapy, metabolism)
• Inflammation (chemically induced, drug therapy, metabolism)
• Interferon-gamma (metabolism)
• Liver (drug effects, metabolism)
• Mice
• Mice, Inbred C57BL
• Mitogen-Activated Protein Kinases (antagonists & inhibitors)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type III (metabolism)
• Obesity (complications)
• Piperazines (pharmacology, therapeutic use)
• Pyrroles (pharmacology, therapeutic use)
• RNA, Messenger (metabolism)
• Random Allocation
• Tumor Necrosis Factor-alpha (metabolism)