Possible neuroprotective mechanisms of clove oil against icv-colchicine induced cognitive dysfunction.

BACKGROUND: Alzheimer's disease (AD), a common neurodegenerative disorder, recognized to be a major cause of dementia. The aim of the present study was to investigate the neuroprotective mechanisms of clove oil in intracerebroventricular (icv)-colchicine induced cognitive dysfunction in rats. METHODS: Single bilateral icv-colchicine (15µg/5µl) was administered, followed by drug treatment with clove oil (0.05ml/kg and 0.1ml/kg, ip), minocycline (25 and 50mg/kg, ip) and their combinations for a period of 21 days. Various neurobehavioral parameters followed by biochemical, acetylcholinesterase (AChE) level and mitochondrial respiratory enzyme complexes (I-IV) were assessed. RESULTS: Colchicine icv administration significantly impaired cognitive performance in Morris water maze (MWM) causes oxidative stress, raised AChE level, caused neuroinflammation and mitochondrial dysfunction as compared to sham treatment. Treatment with clove oil (0.05ml/kg and 0.1ml/kg) and minocycline (25 and 50mg/kg) alone significantly improved cognitive performance as evidenced by reduced transfer latency and increased time spent in target quadrant (TSTQ) in MWM task, reduced AChE activity, oxidative damage (reduced lipid peroxidation levels, nitrite level and restored glutathione levels) and restored mitochondrial respiratory enzyme complex (I-IV) activities as compared to icv-colchicine treatment. Further, combinations of clove oil (0.1ml/kg) with minocycline (50mg/kg) significantly modulate the neuroprotective effect of clove oil as compared to their effect alone. CONCLUSION: The present study highlights that the major neuroprotective effect of clove oil due to its mitochondrial restoring and anti-oxidant properties along with a microglial inhibitory mechanism.

Ameliorative potential of pioglitazone and ceftriaxone alone and in combination in rat model of neuropathic pain: Targeting PPARγ and GLT-1 pathways.

BACKGROUND: The relation between glutamate homeostasis and PPAR gamma has got tremendous importance in nerve trauma and pain. Present study has been designed to elucidate the interaction between the GLT-1 activator (ceftriaxone) and PPAR gamma agonist (pioglitazone) in the spinal nerve ligation induced neuropathic pain. METHODS: Male SD rats were subjected to spinal nerve ligation to induce neuropathic pain. Pioglitazone, ceftriaxone and their combination treatments were given for 28 days. Various behavioral, biochemical, neuroinflammatory and apoptotic mediators were assessed subsequently. RESULTS: In the present study, ligation of L5 and L6 spinal nerves resulted in marked hyperalgesia and allodynia to different mechanical and thermal stimuli. In addition there is marked increase in oxidative-nitrosative stress parameters, inflammatory and apoptotic markers in spinal cord of spinal nerve ligated rats. Treatment with pioglitazone and ceftriaxone significantly prevented these behavioral, biochemical, mitochondrial and cellular alterations in rats. Further, combination of pioglitazone (10mg/kg, ip) with ceftriaxone (100mg/kg, ip) significantly potentiated the protective effects as compared to their effects per se. CONCLUSION: Based on these results we propose that possible interplay between the neuroprotective effects of pioglitazone and ceftriaxone exists in suppressing the behavioral, biochemical, mitochondrial, neuroinflammatory and apoptotic cascades in spinal nerve ligation induced neuropathic pain in rats.

Neuroprotective mechanism of losartan and its interaction with nimesulide against chronic fatigue stress.

Potential role of angiotensin-II and cyclooxygenase have been suggested in the pathophysiology of chronic fatigue stress. The present study has been designed to evaluate the neuroprotective effect of losartan and its interaction with nimesulide against chronic fatigue stress and related complications in mice. In the present study, male Laca mice (20-30 g) were subjected to running wheel activity test session (RWATS) for 6 min daily for 21 days. Losartan, nimesulide and their combinations were administered daily for 21 days, 45 min before being subjected to RWATS. Various behavioral and biochemical and neuroinflammatory mediators were assessed subsequently. 21 days RWATS treatment significantly decreased number of wheel rotations/6 min indicating fatigue stress like behaviors as compared to naive group. 21 days treatment with losartan (10 and 20 mg/kg, ip), nimesulide (5 and 10 mg/kg, po) and their combinations significantly improved behavior [increased number of wheel rotations, reversal of post-exercise fatigue, locomotor activity, antianxiety-like behavior (number of entries, latency to enter and time spent in mirror chamber), and memory performance (transfer latency in plus-maze performance task)], biochemical parameters (reduced serum corticosterone, brain lipid peroxidation, nitrite concentration, acetylcholinesterase activity, restored reduced glutathione levels and catalase activity) as compared to RWATS control. Besides, TNF-α, CRP levels were significantly attenuated by these drugs and their combinations as compared to control. The present study highlights the role of cyclooxygenase modulation in the neuroprotective effect of losartan against chronic fatigue stress-induced behavioral, biochemical and cellular alterations in mice.

Current knowledge and pharmacological profile of berberine: An update.

Berberine, a benzylisoquinoline alkaloid, occurs as an active constituent in numerous medicinal plants and has an array of pharmacological properties. It has been used in Ayurvedic and Chinese medicine for its antimicrobial, antiprotozoal, antidiarrheal and antitrachoma activity. Moreover, several clinical and preclinical studies demonstrate ameliorative effect of berberine against several disorders including metabolic, neurological and cardiological problems. This review provides a summary regarding the pharmacokinetic and pharmacodynamic features of berberine, with a focus on the different mechanisms underlying its multispectrum activity. Studies regarding the safety profile, drug interactions and important clinical trials of berberine have also been included. Clinical trials with respect to neurological disorders need to be undertaken to exploit the beneficiary effects of berberine against serious disorders such as Alzheimer's and Parkinson's disease. Also, clinical studies to detect rare adverse effects of berberine need to be initiated to draw a complete safety profile of berberine and strengthen its applicability.

Possible involvement of nitric oxide modulatory mechanism in the protective effect of retigabine against spinal nerve ligation-induced neuropathic pain.

Decreasing the hyperexcitability of neurons through opening of voltage-gated potassium (Kv7) channels has been suggested as one of the protective mechanisms in the effective management of neuropathic pain. Reactive oxygen/nitrogen species are well implicated in the pathophysiology of neuropathic pain. Further, M current generated by opening of voltage-gated potassium channels (Kv7) has been modulated by reactive oxygen/nitrogen species. The present study has been designed to elucidate the nitric oxide modulatory mechanism in the protective effect of retigabine against spinal nerve ligation-induced neuropathic pain in rats. Ligation of L5/L6 spinal nerves resulted in alterations in various behavioral (as evident from marked increase in thermal and mechanical hyperalgesia, and allodynia) and biochemical (raised lipid peroxidation, nitrite, and depletion of GSH, SOD, and catalase) cascades as compared to sham treatment. Administration of retigabine (10 mg/kg) for 28 days attenuated these behavioral and biochemical cascades as compared to control rats. Further, L-arginine (100 mg/kg) pretreatment with retigabine (5 mg/kg) significantly reversed the protective effect of retigabine in spinal nerve-ligated rats. However, L-NAME (10 mg/kg) pretreatment with retigabine (5 mg/kg) significantly potentiated their protective effects which were significant as compared to their effect per se, respectively. The present study highlights the possible involvement of nitric oxide modulatory mechanism in the protective effect of retigabine against L5/L6 spinal nerve ligation-induced behavioral and biochemical alterations in rats.