Cognitive enhancing effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on learning and memory.

OBJECTIVE: The present study was designed to investigate cognitive enhancing property of angiotensin-converting enzymes inhibitors (ACEI) and angiotensin receptor blockers (ARBs) in rats. MATERIALS AND METHODS: The elevated plus maze (EPM), passive avoidance test (PAT), and water maze test (WMT) were used to assess cognitive enhancing activity in young and aged rats. Ramipril (10 mg/kg, p.o.), perindopril (10 mg/kg, i.p), losartan (20 mg/kg, i.p), and valsartan (20 mg/kg, p.o) were administered to assess their effect on learning and memory. Scopolamine (1 mg/kg, i.p) was used to impair cognitive function. Piracetam (200 mg/kg, i.p) was used as reference drug. RESULTS: All the treatments significantly attenuated amnesia induced by aging and scopolamine. In EPM, aged and scopolamine-treated rats showed an increase in transfer latency (TL) whereas, ACEI and ARBs showed a significant decrease in TL. Treatment with ACEI and ARBs significantly increased step down latencies and decreased latency to reach the platform in target quadrant in young, aged and scopolamine-treated animals in PAT and WMT, respectively. The treatments inhibited acetylcholinesterase (AChE) enzyme in the brain. Similarly, all the treatments attenuated scopolamine-induced lipid peroxidation and normalize antioxidant enzymes. CONCLUSION: The results suggest that the cognitive enhancing effect of ACEI and ARBs may be due to inhibition of AChE or by regulation of antioxidant system or increase in formation of angiotensin IV.

Protective effect of sitagliptin and rosuvastatin combination on vascular endothelial dysfunction in type-2 diabetes.

The present investigation aimed to evaluate the protective effects of sitagliptin, glimepiride, rosuvastatin and their combinations on oxidative stress and endothelial dysfunction in the aortic tissues in fructose-fed type-2 diabetic rats. Sitagliptin (20 mg/kg, p.o.), glimepiride (2 mg/kg, p.o.), rosuvastatin (5 mg/kg, p.o.) and their combinations were administered for 6 w after induction of diabetes by fructose (66%, w/v solution, p.o. for 8 w) in wistar rats. The effects were examined on body weight, serum glucose, triglyceride, cholesterol, blood pressure, heart rate, nitric oxide and antioxidant defensive enzymes. After completion of treatment schedule, the blood pressure was determined by invasive method and vascular reactivity was tested with adrenaline, noradrenaline and phenylephrine. Endothelial dysfunction was determined by acetylcholine and sodium nitroprusside-induced vasorelaxation studies on isolated rat aortas. Long term treatments significantly decreased body weight gain, serum glucose, triglyceride and cholesterol levels; normalize the heart rate, and blood pressure in fructose fed rats. The treatments significantly improved vascular reactivity to catecholamines with reduction in elevated blood pressure in type-2 diabetic rats. The significant improvement in the relaxant response to acetylcholine and sodium nitroprusside was obtained on isolated aortas. All the treatments were effective in restoring defensive antioxidant enzymes. Sitagliptin and rosuvastatin were able to reverse endothelial dysfunction in type-2 diabetes, but better ameliorating potential was found when used in combination.

Protective effect of nebivolol on reserpine-induced neurobehavioral and biochemical alterations in rats.

Reserpine-induced orofacial dyskinesia is a model that shares some mechanists' aspects with tardive dyskinesia whose pathophysiology has been related to oxidative stress. The present study was aimed to explore neuroprotective effects of nebivolol, an antihypertensive agent, on reserpine-induced neurobehavioral and biochemical alterations in rats. Reserpine (1mg/kg, s.c.) was used to induce neurotoxicity. Administration of reserpine for 3 days every other day significantly increased the vacuous chewing movements (VCMs), tongue protrusions (TPs) and reduced the locomotor activity in rats. Pre-treatment with nebivolol (5 and 10mg/kg, p.o. for 5 days) showed dose dependant decrease in VCMs and TP induced by reserpine. Nebivolol also showed significant improvement in locomotor activity. Reserpine significantly increased lipid peroxidation and reduced the levels of defensive antioxidant enzymes like catalase (CAT), superoxide dismutase (SOD) and reduced glutathione (GSH) in rat brain. Nebivolol reversed these effects of reserpine on oxidative stress indices; indicating amelioration of oxidative stress in rat brains. The results of the present study indicated that nebivolol has a protective role against reserpine-induced orofacial dyskinesia. Thus, the use of nebivolol as a therapeutic agent for the treatment of tardive dyskinesia may be considered.

Protective effect of Morus alba leaves on haloperidol-induced orofacial dyskinesia and oxidative stress.

Long-term treatment with haloperidol, a typical neuroleptic, induces neurodegeneration caused by excitotoxicity and oxidative stress, which play an important role in the development of orofacial dyskinesia. In the present investigation, an attempt has been made to examine the effect of a concomitant treatment of methanol extract of Morus alba Linn. (Moraceae) leaves (100-300 mg/kg, i.p.) and haloperidol (1 mg/kg, i.p.) on an animal model of tardive dyskinesia. Rats were treated for 21 days with haloperidol and Morus alba extract; vacuous chewing movements and tongue protrusions were counted. The extract attenuated the increase in vacuous chewing movements and tongue protrusions induced by haloperidol, which were quantified on day 22. The extract showed a marked effect on behavioral parameters altered by haloperidol treatment. Similar treatment with extract attenuated haloperidol-induced lipid peroxidation and nitrite and normalized superoxide dismutase, catalase, and protein in comparison to the control group. The results suggest a protective effect of Morus alba extract against haloperidol-induced orofacial dyskinesia and oxidative stress.

Effect of Hibiscus rosa sinensis on reserpine-induced neurobehavioral and biochemical alterations in rats.

Effect of methanolic extract of Hibiscus rosa sinensis (100-300 mg/kg) was studied on reserpine-induced orofacial dyskinesia and neurochemical alterations. The rats were treated with intraperitoneal reserpine (1 mg/kg, ip) for 3 days every other day. On day 5, vacuous chewing movements and tongue protrusions were counted for 5 min. Reserpine treated rats significantly developed vacuous chewing movements and tongue protrusions however, coadministration of Hibiscus rosa sinensis roots extract (100, 200 and 300 mg/kg, per orally) attenuated the effects. Biochemical analysis of brain revealed that the reserpine treatment significantly increased lipid peroxidation and decreased levels of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GSH), an index of oxidative stress process. Coadministration of extract significantly reduced the lipid peroxidation and reversed the decrease in brain SOD, CAT and GSH levels. The results of the present study suggested that Hibiscus rosa sinensis had a protective role against reserpine-induced orofacial dyskinesia and oxidative stress.

Effect of Morus alba L. (mulberry) leaves on anxiety in mice.

OBJECTIVE: The aim of the present work is to evaluate the anxiolytic effect of a methanolic extract of Morus alba L. leaves in mice. MATERIALS AND METHODS: The hole-board test, elevated plus-maze paradigm, open field test, and light/dark paradigm were used to assess the anxiolytic activity of the methanolic extract of M. alba L. Morus alba extract (50, 100, and 200 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) were administered 30 min before the tests. RESULTS: The results showed that the methanolic extract of M. alba significantly increased the number and duration of head poking in the hole-board test. In the elevated plus-maze, the extract significantly increased the exploration of the open arm in similar way to that of diazepam. At a dose of 200 mg/kg i.p. the extract significantly increased both the time spent in and the entries into the open arm by mice. Further, in the open field test, the extract significantly increased rearing, assisted rearing, and number of squares traversed, all of which are demonstrations of exploratory behavior. In the light/dark paradigm, the extract produced significant increase in time spent in the lighted box as compared to vehicle. The spontaneous locomotor activity count, measured using an actophotometer, was significantly decreased in animals pretreated with M. alba extract, indicating a remarkable sedative effect of the plant. CONCLUSION: The results of the present study suggest that a methanolic extract of M. alba leaves may possess an anxiolytic effect.