Eugenosedin-A prevents high-fat diet increased adhesion molecules through inhibition of MAPK- and p65-mediated NF-κB pathway in rat model

Abstract

Taken together, hyperlipidaemia enhances the expression of adhesion molecules and ACAT-1 protein, and eugenosedin-A ameliorates those increases. Through inhibition of MAPK- and p-65-mediated NF-κB pathway, eugenosedin-A decreases the quantity of adhesion molecules.

Eugenosedin‐A improves glucose metabolism and inhibits MAPKs expression in streptozotocin/nicotinamide‐induced diabetic rats

“…Eu‐A treatment improved the body weight and blood glucose levels, and enhanced the insulin concentrations. We previously reported that Eu‐A ameliorated HFD‐induced hyperglycemia, hyperinsulinemia, hyperlipidemia, lipid peroxidation, and vascular disorders [13–16]. In this study, Eu‐A prevented STZ/nicotinamide‐reduced insulin receptor and its cascade proteins (IR, IRS‐1, IRS‐2, AMPK, GLUT4), modulated glycolysis (GCK, PPAR‐γ) and glycogenesis (GSK) proteins and stimulated MAPKs (p38, ERK, JNK) and inflammatory p65 proteins.…”

“…Treatment with Eu‐A not only prevented STZ/nicotinamide‐induced hyperglycemia, MAPKs and inflammatory p65 activation, but also stimulated insulin secretion. In our previous reports, we demonstrated that Eu‐A ameliorated HFD‐induced inflammation by reducing the MAPKs pathway [14,15]. Thus, we suggested that Eu‐A prevents STZ/nicotinamide‐induced T2DM in part by blockade of the MAPKs‐ and p65‐mediated inflammatory cascade.…”

“…The homogenized liver tissues were identified by insulin receptor (IR, 95 kDa), insulin receptor substrate‐1 (IRS‐1, 180 kDa), IRS‐2 (185 kDa), AMP‐activated protein kinase (AMPK, 63 kDa), glucose transporter‐4 (GLUT‐4, 50 kDa), glucokinase (GCK, 56 kDa), glycogen synthase kinase (GSK, 51 kDa), peroxisome proliferator‐activated receptor γ (PPAR‐γ, 54 kDa), p38 (38 kDa), ERK (42 kDa), JNK (46 kDa), and p65 (65 kDa) antibodies (Santa Cruz Biotechnology, Santa Cruz, CA; 1:500 dilution) and IgG conjugated antibody (Santa Cruz Biotechnology, Santa Cruz, CA; 1:10,000 dilution). The relative protein expression in each tissue was quantified by densitometric scanning of the western blots using Image‐Pro Plus software (Media Cybernetics, Rockville, MD) as previously described [13–15].…”

“…Eugenosedin‐A (Eu‐A), synthesized by our laboratory, is a 5‐HT 1B/2A and α 1 /α 2 /β 1 ‐adrenergic blocker that can decrease blood pressure and heart rate [10], diminish inflammation, scavenge free radicals [11], and inhibit platelet aggregation [12]. Eu‐A reduced obesity‐related hyperglycemia, hyperinsulinemia, hyperlipidemia [13], inflammation, and adhesion molecules [14–16]. Eu‐A also inhibited high‐fat diet (HFD)‐induced vascular and endothelial dysfunction and oxidative stress by attenuating α 1‐ adrenoceptor/5‐HT activity and NADPH oxidase [16].…”

Ethanol extract of Zhongtian hawthorn lowers serum cholesterol in mice by inhibiting transcription of 3-hydroxy-3-methylglutaryl-CoA reductase via nuclear factor-kappa B signal pathway

“…Previous studies have demonstrated that increased NF-jB signal is correlated with obesity and numerous metabolic disorders, and plays important roles in the high-fat diet-induced hypercholesterolemia and atherosclerosis, whereas suppression of NF-jB signal pathway is involved in the antiatherosclerosis and cholesterol-lowering effects of statins and other pharmacologic agents. [34][35][36][37][38][39][40] Furthermore, it has been demonstrated that there is a cross-talk between MyD88-NFjB and SCAP-SREBP2 pathways in the lipopolysaccharides-induced inflammatory response, upregulation of HMGCR, and cholesterol disorders, 41 and the promoter region of both SREBP-2 and HMGCR contains putative NF-jB response elements and they are all direct target genes of NF-jB. 42,43 Similarly, here, our results showed that the repression of NF-jB pathway was also implicated in the transcriptional inhibition of HMGCR by Zhongtian hawthorn ethanol extract.…”