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Methods Chemicals and reagentsAll chemicals except those noted below were purchased from Abstract Background: Peperomia pellucida is used as a medicinal plant and as an antihypertensive remedy. We investigated the possible mechanism of this action and its impact on cytochrome P450 (CYP) enzyme activity.Methods: Mean arterial pressure and heart rate were recorded via cannulation of the carotid artery on anaesthetized, normotensive Sprague-Dawley rats following intravenous administration of Peperomia pellucida aqueous (10-30 mg/ kg) plant extract (PPAE). Recordings of the contractile activity of the aortic rings to the extract (1.9-8.6 mg/ml) were done using standard organ bath techniques. Impact on CYP3A4 and CYP2D6 enzyme activities was investigated using human liver and heterologously expressed microsomes. Results:We observed a dose-dependent reduction in systolic, diastolic, MAP and HR. Pre-treatment with atropine (2 mg/kg) and propranolol (1 mg/kg) but not mepyramine (2 mg/kg) significantly (p<0.05) reduced the hypotensive and negative chronotropic activities caused by the extract, while L-NAME (5 mg/kg) completely abolished it. PPAE significantly (p<0.05) relaxed the phenylephrine (10 -9 -10 -4 M) and KCl-induced contractions and displayed moderate inhibition of CYP3A4 enzyme activity with IC 50 values of 0.466 ± 0.126 mg/mL and 0.153 ± 0.054 mg/mL, respectively using heterogenously expressed CYP3A4 and human liver microsomes (HLMs) Conclusion: Results suggest dose-dependent hypotensive, bradycardic and vasorelaxant effects of PPAE are mediated through Nitric oxide-dependent mechanisms. The impact on CYPs enzyme activities indicate unlikely adverse drug effect when Peperomia pellucida is consumed with other medications reliant on CYP3A4 metabolism.

Aim: Beneficial effects of virgin coconut oil (VCO) consumption to improve cognition in menopausal females remain inconclusive. This study examined the effect of VCO supplementation in aging cycling and non-cycling rodents to assess its impact on cognition. Methods: Sprague-Dawley rats (10 -18 months) were randomly assigned to a supplemented VCO group (SVCO) that received oral doses of 1.42 mL/kg/day VCO (n = 10) and a non-supplemented (NVCO) group (n = 10). Their performance in a biased Y-maze discriminative learning paradigm was assessed over a 16-week period. Rats were initially allowed 3 minutes to explore the maze (habituated) and subsequently pre-trained in the non-preferred, white chamber to associate the presentation of a tone with a treat (reward). Training involved 4 daily trials initially for 3 weeks during which rats were rewarded if they entered the white arm within 15 sec after tone presentation. Time (days) to attain at least 75% correct responses (CR) determined acquisition latency (AL). Memory retention (MR1) of the learned task was assessed following a 1-week break from training and absence of supplementation (session T1). Following an additional 2-week break, supplementation of SVCO animals resumed and continued to week 16. In week 14, all animals received re-training for 1 week (session T2) followed by another 1-week break and subsequent assessment of memory (MR2). Vaginal smear cytology determinations were performed throughout the study to identify cycling and non-cycling rats. Student's t-test and ANOVA with Brown-Forsythe and Tukey's post-hoc tests were used to compare means.

Aim: The effect of patented nutritional supplementation on drug-seeking behavior in cocaine addicted rats during acute drug withdrawal was investigated using a biased Conditioned Place Preference (CPP) paradigm. Method: Twenty-four (24) male Sprague-Dawley rats with pre-conditioned preference for the black chamber of the CPP box were randomly divided into Cocaine (COC) or Saline (SAL) treated groups. Rats (n = 12) treated with cocaine hydrochloride 20 mg/kg/ml, i.p. (COC group) were confined individually to the white chamber on days 1, 3, 5 and 7. On alternate days, they were given 1 ml saline vehicle, i.p. and confined to the black chamber. Control rats (SAL group, n = 12) received only vehicle on all 8 days and were confined on alternate days to the white or black chamber. Positive place preference was confirmed for COC rats, which subsequently received 6 increasing daily doses of cocaine. CPP performances of both COC and SAL rats were recorded following an acute 3-day withdrawal period. All animals were then randomly assigned to rats fed either chow reconstituted with the nutritional supplement (COC-S and SAL-S) or standard rat chow (COC-N and SAL-N) for 8 weeks, followed by final CPP performances. Results: Following supplementation, COC-S rats made significantly less entries and time spent in the white chamber (p < 0.05) compared with COC-N rats. COC-S rats exhibited significant place aversion to the white chamber similar to drug-naive animals; whereas COC-N continued to show positive place preference. Conclusion: Drug-seeking behavior that persisted during cocaine withdrawal was significantly diminished in the nutritionally supplemented.