Rosuvastatin and co-enzyme Q10 improve high-fat and high-fructose diet-induced metabolic syndrome in rats via ameliorating inflammatory and oxidative burden.

The prevalence of metabolic syndrome (MetS) has been rising alarmingly and it has now become a global concern causing an enormous economic burden on the health care system. MetS is generally linked to complications in lipid metabolism, oxidative stress and low grade inflammation. The aim of the current study was to evaluate the effect of rosuvastatin, co-enzyme Q10 (CoQ10), and their combination on blood pressure, blood sugar, dyslipidemia, and liver function in rats with MetS induced by high fructose and high fat diet (HF-HFD) and the possible underlying mechanism. Oral administration of rosuvastatin (10 mg/kg/day), CoQ10 (10 mg/kg/day) and their combination for 4 weeks in HF-HFD-fed rats elevated serum high density lipoprotein and reduced glutathione. On the other hand, treatment with rosuvastatin, CoQ10 or their combination decreased the serum levels of malondialdehyde, triglycerides, total cholesterol, and low density lipoprotein-cholesterol as well as systolic blood pressure, body weight and fasting blood glucose level. In addition, the drugs or their combination declined serum pro-inflammatory cytokines, namely tumor necrosis factor-α and interleukin-1ß. In conclusion, our results showed that rosuvastatin or CoQ10 protected against HF-HFD-induced MetS through the regulation of dyslipidemia, elevated blood glucose, elevated blood pressure, antioxidant defenses and inflammatory response. Rosuvastatin or CoQ10 also alleviated the impairment of liver function that was induced by HF-HFD. Interestingly, CoQ10 augmented rosuvastatin's effect in ameliorating MetS, via exerting synergistic modulatory effects on oxidative stress and inflammation. Thus, rosuvastatin and CoQ10 combination therapy may have possible applications in ameliorating metabolic disorders.

Neuroprotective Effects of Telmisartan and Nifedipine Against Cuprizone-Induced Demyelination and Behavioral Dysfunction in Mice: Roles of NF-κB and Nrf2.

Multiple sclerosis is a chronic inflammatory neurodegenerative disease of the central nervous system which injures the myelin sheath. Telmisartan and nifedipine are antihypertensive drugs that recently showed neuroprotective properties against neurodegenerative diseases. This study evaluated the neuroprotective effect of telmisartan or nifedipine in cuprizone-induced demyelination in mice by examining the underlying mechanisms. C57BL/6 mice received a diet containing 0.7% (w/w) cuprizone for 7 days followed by 3 weeks on a 0.2% cuprizone diet. Telmisartan (5 mg/kg/day, p.o.) or nifedipine (5 mg/kg/day, p.o.) was administered for 3 weeks starting from the second week. Telmisartan or nifedipine improved locomotor activity and enhanced motor coordination as demonstrated by open field, rotarod, and grip strength tests. Furthermore, telmisartan or nifedipine restored myelin basic protein mRNA and protein expression and increased luxol fast blue-staining intensity. Telmisartan or nifedipine attenuated cuprizone-induced oxidative stress and apoptosis by decreasing brain malondialdehyde and caspase-3 along with restoring reduced glutathione and brain-derived neurotrophic factor levels. Telmisartan or nifedipine exerted an anti-inflammatory effect by reducing the expression of nuclear factor kappa B (NF-κB p65) as well as pro-inflammatory cytokines and elevating the expression of IκB-α. In parallel, telmisartan or nifedipine upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and the levels of heme oxygenase-1 and NADPH quinone oxidoreductase 1 enzymes. In conclusion, the current study provides evidence for the protective effect of telmisartan and nifedipine in cuprizone-induced demyelination and behavioral dysfunction in mice possibly by modulating NF-κB and Nrf2 signaling pathways.