Neuroprotective Effects of Caffeine on a Maternally Separated Parkinsonian Rat Model

Early-life stress has been shown to disrupt the programming of the hypothalamic-pituitary-adrenal (HPA) axis which may have severe consequences in the development of neurological disorders later on in life. Prolonged early-life stressful events produce an exaggerated stress hormone response in the adult offspring. Chronic stress and elevated corticosterone levels have been found to exaggerate functional deficits and accelerate loss of dopamine producing neurons in a rat model of Parkinson’s disease. We investigated the neuroprotective effects of caffeine on 6-OHDA lesioned rats that were exposed to maternal separation stress. We examined behaviour of animals before and after the infusion of 6-OHDA using the step and cylinder tests. We also measured dopamine concentration in the striatum, mitochondrial membrane potential in the striatum and the total antioxidant capacity in blood plasma. Maternally separated rats displayed an impaired ability to initiate movement in the step test and a decreased percentage impaired limb use in the cylinder test. In the rats that received caffeine these motor deficits were ameliorated. Maternal separation exaggerated the lesion caused by 6-OHDA injection. However, the neuroprotective effects of caffeine were evident in both the stressed and non-stressed rats as shown by the higher dopamine concentration and total antioxidant capacity on caffeine treated rats. Maternally separated rats had higher mitochondrial membrane permeability when compared to the caffeine treated rats. We therefore conclude that caffeine ameliorated the neurodegeneration associated with 6-OHDA injection in maternally separated animals.

Asiatic acid-pectin hydrogel matrix patch transdermal delivery system influences parasitaemia suppression and inflammation reduction in P. berghei murine malaria infected Sprague-Dawley rats

Objective: To report the influence of transdermal delivery of asiatic acid(AA) in Plasmodium berghei-infected Sprague Dawley rats on physicochemical changes, %parasitaemia and associated pathophysiology. Methods: A topical once-off AA(5, 10, and 20 mg/kg)- or chloroquine(CHQ)-pectin patch was applied on the shaven dorsal neck region of Plasmodium berghei-infected Sprague Dawley rats(90-120 g) on day 7 after infection. Eating and drinking habits, weight changes, malaria effects and %parasitaemia were compared among animal groups over 21 d. Results: AA-pectin patch application preserved food and water intake together with %weight gain. All animals developed stable parasitaemia(15%-20%) by day 7. AA doses suppressed parasitaemia significantly. AA 5 mg/kg patch was most effective. AA and CHQ displayed bimodal time-spaced peaks. CHQ patch had a longer time course to clear parasitaemia. Conclusions: AA influences bio-physicochemical changes and parasitaemia suppression in dose dependent manner. In comparison by dose administered, AA has much better efficacy than CHQ. AA may be a useful antimalarial. AA and CHQ displays bimodal peaks suggesting possible synergism if used in combination therapy.

The Antihypertensive Effect of Hydro-methanolic Extract of Tulbaghia acutiloba Harv.in L-NAME induced Hypertensive Rats

Background:Traditional use of Tulbaghia acutiloba(TA)in South Africa includes treating various illnesses,such as infectious diseases and hypertension.However,the effect of this indigenous plant on renal and haematological parameters(as indicators of antihypertensive efficacy)has not been investigated yet.Objective:This study aimed to evaluate the change of renal and haematological parameters after treatment with the hydro-methanolic extract of the leaf of Tulbaghia acutiloba Harv.in L-NAME-induced hypertensive rats.Methods:Male albino Wistar rats received an oral dose of 50 mg·kg^(-1)body weight(bw)of N𝜔-Nitro-L-arginine methyl ester hydrochloride(L-NAME)daily for 5 weeks.Five groups(7 animals in each group)were identified to receive different treatments as concurrent daily doses of(40,60 and 80 mg·kg^(-1)bw),ramipril(10 mg·kg^(-1)bw)(positive control)and water(hypertension model).Mean arterial blood pressure was measured weekly using the tail-cuffmethod.A 24-hour urine sample was collected for each rat weekly.On day 36,the rats were euthanized,and blood samples were collected for the determination of renal function and haematological analysis.Kidney mRNA gene expression was performed for NF-kB,Ho1 and eNos.Results:The treatment of the hypertensive rats with TA resulted in a significant reduction in the mean arterial blood pressure,with a pronounced effect observed in the 80 mg·kg^(-1)dose of TA compared to the positive control.The TA-treated group showed increased creatinine clearance(Ccr),urine volume and a reduction in serum crea-tinine,proteinuria and urine protein-creatinine ratio(UPr/UCr).TA treatment also decreased lipid peroxidation in renal tissues and erythrocytes while increasing SOD,CAT,GSH and NO levels.Moreover,red cell distribu-tion width(RDW),white blood cells(WBC),neutrophil to lymphocyte ratio(NLR),lymphocyte to monocyte ratio(LMR),platelet and mean platelet volume(MPV)were significantly reduced in the TA and ramipril treated groups with the maximum effect occurring at the dose of 80 mg·kg-1 of TA.No significant difference was observed in the haemoglobin levels in all experimental groups.TA administration resulted in a significant decrease in renal NF-kB gene expression while increasing Ho1 and eNos gene expression in renal tissues.Conclusion:TA extract improved renal function and haematological profile(markers for the antihypertensive efficacy)in L-NAME-induced hypertensive rats.