zerumbone and Hyperlipidemias

Hyperlipidaemia and cognitive dysfunction (CD) are the two public health concerns. Though hyperlipidaemia has been comprehensively studied in respect to CVD, its role on CD needs to be explored. Hence, we evaluated hyperlipidaemia as a risk factor for CD and the efficacy of EPA (20 : 5n-3) + DHA (22 : 6n-3) and zerumbone (Z) in modulating CD under hyperlipidaemic conditions. Male Wistar rats (Rattus norvegicus) were fed control, high-fat (HF), high-fat + fish oil (HF + F), high-fat + zerumbone (HF+Z) and high-fat + fish oil + zerumbone (HF+F+Z) containing diets. After a 30 d feeding trial, memory parameters (Morris water maze, elevated plus maze (transfer latency) and T-maze (spontaneous alteration)) and locomotor skills (open field test and rotarod test) were assessed. Hyperlipidaemia significantly (P < 0·05) reduced memory and motor coordination skills compared with control. However, the administration of EPA + DHA and zerumbone significantly (P < 0·05) restored the hyperlipidaemia-induced loss of memory and motor coordination skills. Collectively, our data imply that hyperlipidaemia causes CD by decreasing memory and motor coordination skills, and administration of EPA + DHA and zerumbone prevents hyperlipidaemia-induced CD. The augmented effect of EPA + DHA, together with zerumbone, discloses a promising strategy for lowering the severity of CD in hyperlipidaemic conditions.

Topics: Animals; Cognition; Cognitive Dysfunction; Diet, High-Fat; Disease Models, Animal; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fish Oils; Hyperlipidemias; Male; Morris Water Maze Test; Motor Skills; Nootropic Agents; Rats; Rats, Wistar; Risk Factors; Sesquiterpenes

Oxidative stress (OS) plays a vital role in the pathogenesis of cognitive disorders. In this study, brain antioxidant defense dysregulation as a consequence of hyperlipidemia, and the efficacy of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA), and zerumbone (Z) in their modulation are assessed.. Male Wistar rats are fed control, high-fat (HF), HF + fish oil (HF+F), HF + zerumbone (HF+Z), and HF + fish oil + zerumbone (HF+F+Z) diet for 60 days. Markers of OS, antioxidant enzymes, monoamine oxidase, nuclear factor (erythroid-derived 2)-like 2 (NRF-2), nitric oxide-2 (NOS-2), inter cellular adhesion molecule-1 (ICAM-1), and neurotrophins are measured. Hyperlipidemia increases OS, decreases antioxidant enzyme activity, increases monoamine oxidase activity, increases NOS-2 and ICAM-1 expression, decreases NRF-2 activation, decreases nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) levels in the brain compared to control. While EPA+DHA and zerumbone significantly (p < 0.05) restores the perturbations induced by hyperlipidemia.. It is concluded that hyperlipidemia cause OS by decreasing the activity of brain antioxidant enzymes via the downregulation of NRF-2. The reduced brain neurotrophins in hyperlipidemia indicate its potential risk on cognitive attributes. EPA+DHA, together with zerumbone, positively modulates hyperlipidemia induced brain dysfunction thereby offering promising therapeutic strategy.

Topics: Animals; Antioxidants; Biomarkers; Brain; Docosahexaenoic Acids; Down-Regulation; Eicosapentaenoic Acid; Enzymes; Hyperlipidemias; Intercellular Adhesion Molecule-1; Male; Nerve Growth Factors; NF-E2-Related Factor 2; Oxidative Stress; Rats, Wistar; Sesquiterpenes

We investigated the effects of zerumbone, a natural cyclic sesquiterpene of Zingiber zerumbet Smith, on high-fat diet (HFD)-induced hyperlipidemic hamsters. After being fed HFD for 2 weeks, Syrian golden hamsters were dosed orally with zerumbone (25, 50, and 100 mg/kg) once daily for 8 weeks. Decreased plasma levels of TC, TG and LDL-C, as well as the concentrations of hepatic lipids, with a simultaneous increase in fecal lipids were found. The ratios of LDL-C/HDL-C and TC/HDL-C were elevated by zerumbone. Zerumbone exhibited the ability to decreased hepatic mRNA levels of fatty acid synthase, malic enzyme, sterol-regulatory element binding protein and 3-hydroxy-3-methyl-glutaryl-CoA reductase reductase. The hepatic mRNA expression of peroxisome proliferator-activated receptor α, together with its target gene carnitine palmitoyl transferase and acyl-CoA oxidase were also upregulated by zerumbone. Zerumbone is effective to improve dyslipidemia by modulating the genes expression involving in the lipolytic and lipogenic pathways of lipids metabolism.

Topics: Animals; Body Weight; Carnitine O-Palmitoyltransferase; Diet, High-Fat; Disease Models, Animal; Eating; Feces; Gene Expression Regulation; Hyperlipidemias; Lipase; Lipid Metabolism; Lipids; Lipolysis; Liver; Male; Mesocricetus; Sesquiterpenes; Sterol Regulatory Element Binding Protein 1; Zingiberaceae