METHODS: The extract of D. linearis leaves (CEDL; 50, 250 and 500 mg/kg) was orally administered to rats for 7 consecutive days followed by the oral administration of 3 g/kg PCM to induce liver injury. Blood was collected for liver function analysis while the liver was obtained for histopathological examination and endogenous antioxidant activity determination. The extract was also subjected to antioxidant evaluation and phytochemicals determination via phytochemical screening, HPLC and UPLC-HRMS analyses.
RESULTS: CEDL exerted significant (p
ABSTRACT: Oxidative stress-mediated lipid peroxidation is a known cause of endothelial injury or dysfunction. Deprivation of rapid eye movement (REM) sleep is associated with oxidative stress. To date, the pathogenesis of increased blood pressure after sleep deprivation remains poorly understood, particularly in the REM sleep phase. Our aim was to investigate the effects of REM sleep deprivation on blood vessels in the REM sleep-deprived rat model. Twenty-eight male Sprague-Dawley rats were divided into four equal groups: free-moving control rats, rats deprived of REM sleep for 72 h (REMsd), tank control rats and 72 h sleep-recovered rats after 72 h of REM sleep deprivation. The rats were deprived of REM sleep using the inverted flowerpot technique. Food consumption, body weight gain and systolic blood pressure were monitored. At the end of the experiment, the descending thoracic aorta was isolated for the measurement of oxidative stress markers. Despite a significant increase in food consumption in the REMsd group compared with the other groups, there was a significant reduction in body weight gain. Systolic blood pressure also showed a significant increase in the REMsd group compared with the other groups. Superoxide dismutase activity was significantly lower and malondialdehyde concentrations significantly higher in the REMsd group compared with the other groups. Increased levels of malondialdehyde are suggestive of lipid peroxidation in the blood vessels, and oxidative stress may be attributed to the initiation of the process. The changes after REM sleep deprivation revert during sleep recovery. In conclusion, the findings of the present study provide convincing evidence that REM sleep deprivation induced lipid peroxidation, leading to endothelial damage.
OBJECTIVES: This study aims (i) to investigate the effects of EGCG on nadolol pharmacokinetics (maximum plasma concentration, time to achieve maximum concentration, area under the time-plasma concentration curve, plasma half-life and total clearance) and subsequently its impact on blood pressure control; and (ii) to identify transcriptional regulatory roles of EGCG on the nadolol intestinal and hepatic drug-transporters in SHR.
METHODS: Male SHR were pre-treated with a daily dose of EGCG (10 mg/kg body weight, i.g.) for 13 days. On day-14, a single dose of nadolol (10 mg/kg body weight) was given to the rats 30 min after the last dose of EGCG administration. Systolic blood pressure (SBP) was measured at 6-h and 22-h post-nadolol administration. Plasma and urinary nadolol concentrations were quantified using high-performance liquid chromatography, and pharmacokinetic parameters were analyzed by using non-compartmental analysis. Hepatic and ileal Oatp1a5, P-gp, and Oct1 mRNA expressions were determined by real-time PCR.
RESULTS: SBP of SHR pre-treated with EGCG and received nadolol was significantly higher than those which were not pre-treated with EGCG but received nadolol. Pre-treatment of EGCG resulted in a marked reduction of plasma nadolol maximum concentration (Cmax) and area under the time-plasma concentration curve (AUC) by 53% and 51% compared to its control. The 14-day treatment with oral EGCG led to a significant downregulation of mRNA levels of ileal Oatp1a5, P-gp, and Oct1 genes by 4.03-, 8.01- and 4.03-fold; and hepatic P-gp, and Oct1 genes by 2.61- and 2.66-fold.
CONCLUSION: These data concluded that exposure to EGCG could lead to reduced nadolol bioavailability and therefore, uncontrolled raised blood pressure and higher risks of cardiovascular events. Our data suggest that the reduced nadolol bioavailability is associated with the downregulation of ileal Oatp1a5 and Oct1 mRNA levels that subsequently lead to poor absorption of nadolol to the systemic circulation.
METHODS: In this study, the rats were randomly divided into six groups i.e., (1) Normal Diet (ND); (2) Normal Diet and 175 mg/kgBW of EECCL (ND + 175 mg/kgBW); (3) Normal Diet and 350 mg/kgBW of EECCL (ND + 350 mg/kgBW); (4) High Fat Diet (HFD); (5) High Fat Diet and 175 mg/kgBW of EECCL (HFD + 175 mg/kgBW); (6) High Fat Diet and 350 mg/kgBW of EECCL (HFD + 350 mg/kgBW). The anti-obesity potential was evaluated through analyses of changes in body weight, visceral fat weight, and blood biochemicals including total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), leptin, insulin, adiponectin, ghrelin and fecal fat content. In addition, metabolite profiling of EECCL was carried out using NMR spectroscopy.
RESULTS: Rats receiving EECCL together with HFD showed significant (p 0.05) different with those of ND rats. Other related obesity biomarkers including plasma lipid profiles, insulin, leptin, ghrelin and adiponectin levels also showed significant improvement (p