Eugenosedin-A prevents hyperglycaemia, hyperlipidaemia and lipid peroxidation in C57BL/6J mice fed a high-fat diet

Abstract

Eugenosedin-A may improve plasma lipid metabolism by increasing low-density lipoprotein receptor and peroxisome proliferator-activated receptor gamma expression and diminishing sterol regulatory element binding protein 1a, fatty acid synthase and sterol-CoA desaturase. Reduction of plasma glucose and lipid levels may, in turn, reduce insulin concentration, which would explain the marked improvement in obesity-related hyperglycaemia and hyperlipidaemia. Furthermore, eugenosedin-A affected malondialdehyde concentration and glutathione peroxidase activity, suggesting it may have anti-peroxidation effects in mice fed a high-fat diet.

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

“…Taken together, these findings suggested that hyperlipidaemia could induce inflammation in the liver. However, in a previous animal study, we found no relationship between hyperlipidaemia and alanine aminotransferase (ALT) and aspartate aminotransferase (AST), though this lack of such a relationship could be due to the short length of time studied (eight weeks) [17] . In this study, we found that eugenosedin‐A significantly reduced the upstream of ERK, JNK and p65 pathways, and iNOS protein expression in the liver of HFD mice, but p38 and PI3K were not significantly reduced.…”

“…In previous studies, we found eugenosedin‐A, a 5‐HT 1B/2A and α 1 / α 2 / β 1 ‐adrenergic blocker, to be capable of reducing inflammation and scavenging free radicals [15,16] . We found that, like atorvastatin, it reduced weight gain and corrected obesity‐associated hyperglycaemia, hyperinsulinaemia, hyperlipidaemia, and lipid peroxidation in mice fed high‐fat diets (HFD) [17] . However, we do not know if eugenosedin‐A, like atorvastatin, can prevent HFD‐induced inflammation.…”

“…Previously, we demonstrated that eugenosedin‐A was able to reduce glucose and lipid levels and indicated that in the future it may be used to improve obesity‐related hyperglycaemia, hyperinsulinaemia, and hyperlipidaemia and scavenge free radicals, which would result in the reduction of obesity‐induced lipid peroxidation [17] . In this study, we have provided further evidence that eugenosedin‐A reduced protein levels of p38, ERK, JNK, Akt/IKKα/p65 and mRNA expression of TNF‐α and IFN‐γ in the liver and aorta, and reduced nitrate in the plasma of mice with hyperlipidaemia‐induced inflammation.…”

“…The membranes were blocked with 1% bovine serum albumin in Tris buffer solution (TBS) containing 0.1% Tween‐20 for 2 h and then incubated with anti‐mouse Tak, Ask, MEK3/6, p38, Src, Ras, MEK1/2, ERK1, Rac, MEK4, JNK1, PI3K, IKK α , Akt, p65, iNOS, COX‐2 and eNOS antibody (Santa Cruz Biotechnology, CA, USA; 1 : 500 dilution) in TBS containing 0.1% Tween‐20 for 2 h. The membrane was washed and finally incubated with a 1 : 1000 dilution of anti‐mouse IgG conjugated to horseradish antibody for 2 h. After successive washings, the immunocomplexes were developed using an enhanced horseradish peroxide/luminol chemiluminescence reaction (ECL Western blotting detection reagents, GE Healthcare Bio‐Sciences Corp.) and exposed to X‐ray film for 10 min. The relative expression of those proteins in each tissue was quantified by densitometric scanning of the Western blots using Image‐pro plus software (Media Cybernetics, MD, USA) as described previously [17] …”

Transcriptional networks implicated in human nonalcoholic fatty liver disease

“…According to the two most significant modules P4 and P8 in the network, we found the top 2 molecules (sulconazole and doxazosin) for these two modules. Interestingly, we found that the roles of doxazosin not only include treating hypertension but also include preventing hepatic steatosis (Menacho-Marquez et al 2013), even alleviating insulin resistance (Shen et al 2009). The drug is widely used to treat hypertension, but its roles in NASH are limited to animal experiment.…”