piperidines and naringenin

Topics: Adenine; Animals; Chromatography, High Pressure Liquid; Drug Interactions; Drug Stability; Flavanones; Limit of Detection; Linear Models; Male; Piperidines; Pyrazoles; Pyrimidines; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Tandem Mass Spectrometry

Darunavir ethanolate (DRV) is an efficient protease inhibitor (PI) used in the treatment of human immunodeficiency virus (HIV) type-1 patients. An isocratic reversed-phase HPLC method was developed to monitor concentration of darunavir in in vitro intestinal fluid samples in everted sac absorption model in the presence of bioenhancers, viz., piperine, quercetin, naringenin. The method was validated and successfully applied to everted sac and pharmacokinetic studies in rats. The absorption profiles of DRV and apparent permeability coefficients were determined. The proposed method was found to be simple, rapid, robust and selective and was applied for continuous ex vivo monitoring of DRV in everted sac absorption studies. Of the three bioenhancers screened at different concentrations, piperine caused highest and significant 1.5-fold increase in apparent permeability of DRV across everted sac tissue. Further, co-administration of piperine significantly increased the maximum plasma concentration of DRV by 1.18-fold confirming the enhancement in its absorption.

Topics: Alkaloids; Animals; Benzodioxoles; Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Darunavir; Flavanones; Intestinal Absorption; Limit of Detection; Linear Models; Male; Piperidines; Polyunsaturated Alkamides; Quercetin; Rats; Rats, Wistar; Reproducibility of Results

Naringenin is a flavone flavonoid possessing antidiabetic, antioxidant and memory improving effects. Therefore, we studied the influence of naringenin against type-2 diabetes-induced memory dysfunction in rats. Type-2 diabetes was induced by high-fat diet and high-fat emulsion for two weeks and a low dose of streptozotocin (35 mg/kg). The memory deficit was assessed by using a novel object recognition paradigm. The changes in oxidative markers and cholinesterase (ChE) levels were evaluated in the hippocampal region. After confirmation of diabetes, naringenin (50mg/kg) treatment was given to animals as a preventive and in another set of experiments naringenin (25 and 50mg/kg) or pioglitazone (5mg/kg) or donepezil (3mg/kg) treatments were started after long-standing diabetes (4 weeks after confirmation). Both the treatment schedules show significant protection and improvement in cognitive behavior against diabetes-induced memory dysfunction and biochemical changes. Also, treatment with pioglitazone and donepezil improved memory performance in rats. Naringenin was found to decrease oxidative stress by depleting elevated lipid peroxide and nitric oxide and elevating reduced glutathione levels. Cholinergic function was improved by naringenin through the inhibition of elevated ChE activity. In conclusion, the present study suggests that naringenin acts as an antioxidant and ChE inhibitor against type-2 diabetes-induced memory dysfunction.

Topics: Animals; Antioxidants; Blood Glucose; Body Weight; Cholinesterase Inhibitors; Cholinesterases; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dietary Fats; Donepezil; Estrogen Antagonists; Fat Emulsions, Intravenous; Flavanones; Glutathione; Hypoglycemic Agents; Indans; Lipid Peroxidation; Male; Memory Disorders; Nitric Oxide; Parasympathetic Nervous System; Pioglitazone; Piperidines; Rats; Rats, Sprague-Dawley; Recognition, Psychology; Thiazolidinediones