Protective effect of melatonin on certain behavioral and biochemical alterations induced by sleep-deprivation in mice

Objective: To explore the effect of melatonin on the behavioral and biochemical parameters in sleep-disturbed mice. Materials and Methods: Male Laca mice (n=6-9/Group) were sleep deprived for 48-hours using grid suspended over water method. Melatonin was administered orally for 5 days (three day before 48-hours sleep deprivation. All the biochemical tests were performed in brain homogenates on fifth day immediately after behavioral observations. Results: Sleep deprivation caused rapid loss of body weight, reduction in locomotor activity, and severe anxiety in animals. Biochemically, sleep deprivation increased lipid peroxidation, nitrite and deplete reduced glutathione and catalase activities in the brains of mice which was significantly as compared to naοve animals (without sleep deprivation). Pre-treatment with melatonin (5 and 10 mg/kg) significantly improved body weight, locomotor activity, and anxiety in animals as compared to control (48-hours sleep-deprived mice). In addition, melatonin also significantly decreased lipid peroxidation, nitrite levels and reversed the depleted catalase and glutathione activity. Conclusion: Melatonin has protective action against sleep deprivation-induced behavioral and biochemical alterations

Protective effect of <i style="">Withania somnifera </i>Dunal on the behavioral and biochemical alterations in sleep-disturbed mice (Grid over water suspended method)

524-528Sleep disruption involves extensive changes in physiological function, including EEG, motor, metabolic, autonomic processes physiological homeostasis and psychological balance that are necessary for physical health. Benzodiazepines are the most widely used drugs for the sleep related problems in spite of their limitations and side effects. Objective of the study was to investigate the protective effect of W. somnifera on the behavioral and biochemical alterations in sleep-disturbed mice. Pretreatment with W. somnifera root extract (100, 200 mg/kg) and diazepam (0.5 mg/kg) significantly protected reduction in body weight, improved the reduced locomotor activity and anxiety levels in animals. Biochemical studies also revealed that W. somnifera (100 and 200 mg/kg) and diazepam (0.5 mg/kg) pretreatment for five days decreased significantly lipid peroxidation, nitrites levels and improved catalase, and reduced glutathione levels. Co-administration of W. somnifera (100 mg/kg) with diazepam (0.5 mg/kg) improved significantly all the biochemical parameters as compared to their effect per se. Preliminary results suggest that Withania root extract can be used in the management sleep loss and associated oxidative stress

Therapeutic potential of catechin as an IKK-β inhibitor for the management of arthritis: In vitro and In vivo approach

Background: Rheumatoid arthritis (RA) is associated with increased levels of cytokines, for instance, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and interleukin-1 (IL-1), which exhibit potent pro-inflammatory effects and are contributing factors to disease progression. A range of cytokines, cell adhesion molecules, and enzymes that are implicated in the debilitating effects of RA are transcribed by nuclear factor kappa. Objectives: The purpose of this research was to characterize the efficacy of “catechin” as an IkappaB kinase-beta (IKK-β) inhibitor in collagen-induced arthritis (CIA) model in mice, as IKK-β is crucial in the transmission of signal-inducible NF-κβ activation. Methods: Arthritis was brought on in Bagg and Albino, but it is written BALB/c (BALB/c) male mice through subcutaneous immunization with bovine type II collagen on days 0 and 21. Catechin is given orally every day after the onset of the disease. Clinical evaluation of the prevalence and severity of the condition was done throughout the trial, and biochemical testing was done at the end (day 42). Results: In vitro findings of the study demonstrated catechin as a potent inhibitor of IKK-β with Half maximal Inhibitory Concentration (IC50) values of 2.90 μM and 4.358 μM in IKK-β and NF-κβ transactivation activity assay, respectively. Furthermore, catechin (dose range of 10–100 mg/kg, p.o.) was effective in reducing disease incidence and clinical signs in a dose-dependent manner, with an Effective Dose for 50% of the population (ED50) value of 79.579 mg/kg. The findings of this study demonstrate dose-dependent efficacy in terms of both disease severity (clinical scoring) and inflammatory markers (biochemical evaluation of the serum and joints). Conclusions: IKK inhibitors are a prospective target for the creation of new therapeutics for arthritis and other inflammatory diseases because it has been suggested that this enzyme is crucial in the pathophysiology of RA. The finding of this study suggests that “catechin” represents a novel inhibitor of IKK-β with promising anti-inflammatory activity

Polish Academy of Sciences Review

Huntington’s disease (HD) is an inherited genetic disorder, characterized by cognitive dysfunction and abnormal body movements called chorea. George Huntington, an Ohio physician, described the disease precisely in 1872. HD is a dominantly inherited disorder, characterized by progressive neurodegeneration of the striatum but also involves other regions, primarily the cerebral cortex. The mutation responsible for this fatal disease is an abnormally expanded and unstable CAG repeat within the coding region of the gene encoding the huntingtin protein. Various hypotheses have been put forward to explain the pathogenic mechanisms of mutant huntingtin-induced neuronal dysfunction and cell death. None of these hypotheses, however, offers a clear explanation; thus, it remains a topic of research interest. HD is considered to be an important disease, embodying many of the major themes in modern neuroscience, including molecular genetics, selective neuronal vulnerability, excitotoxicity, mitochondrial dysfunction, apoptosis and transcriptional dysregulation. A number of recent reports have concluded that oxidative stress plays a key role in HD pathogenesis. Although there is no specific treatment available to block disease progression, treatments are available to help in controlling the chorea symptoms. As animal models are the best tools to evaluate any therapeutic agent, there are also different animal models available, mimicking a few or a larger number of symptoms. Each model has its own advantages and limitations. The present review deals with the pathophysiology and various cascades contributing to HD pathogenesis and progression as well as drug targets, such as dopaminergic, �-amino butyric acid (GABA)ergic, glutamate adenosine receptor, peptidergic pathways, cannabinoid receptor, and adjuvant therapeutic drug targets such as oxidative stress and mitochondrial dysfunction that can be targeted for future experimental study

Neuroprotective effect of MK-801 against intra-striatal quinolinic acid induced behavioral, oxidative stress and cellular alterations in rats

880-892 Huntington’s Disease (HD) is a common neurodegenerative disorder characterized by motor disturbances, subcortical dementia and psychiatric disturbances. Pathogenesis of HD revolves so far around excitatory amino acids as the primary cause of neuronal loss. However, number of recent reports suggests the involvement of excitotoxicity and oxidative damage. In the present study, first the dose of quinolinic acid that mimics the symptoms of HD was standardized and then the neuroprotective effect of MK-801 (noncompetitive NMDAr antagonist) was evaluated against intrastriatalquinolinic acid induced behavioral, oxidative stress and cellular alterations in rats. A single unilateral (ipsilateral striatum) injections of quinolinic acid (100, 200 and 300 nM) were made in to striatum. Animals were tested for motor functions using actophotometer and rotarod apparatus. Quinolinic acid (300 nM) significantly reduced the body weight and caused motor in-coordination and produced oxidative damage in the cortex and striatum as indicated by raised lipid peroxidation, nitrite concentration, depletion of superoxide dismutase, catalase and different glutathione levels. Beside, quinolinic acid (300 nM) significantly altered the mitochondrial enzymes complex levels and caused histopathological alterations in the striatum. MK-801(0.02, 0.04, 0.08 mg/kg, ip) treatment significantly improved body weight, behavioral alterations (locomotor activity and rotarod performance) and attenuated oxidative damage and mitochondrial enzymes complex dysfunction. Besides, MK-801 treatment significantly reversed histopathological alterations in striatum. The results suggest antioxidant and neuroprotective action of MK-801 against the quinolinic acid induced Huntington’s like behavioral, oxidative stress and cellular alterations in rats. </smarttagtype

Effect of nitric oxide in protective effect of melatonin against chronic constriction sciatic nerve injury induced neuropathic pain in rats

664-671Developing a successful treatment strategy for neuropathic pain has remained a challenge among researcher and clinicians. Various animal models have been employed to understand the pathogenic mechanism of neuropathic pain in experimental animals. The present study was designed to explore the possible nitric oxide mechanism in the protective effect of melatonin against chronic constriction injury (CCI) of sciatic nerve in rats. Following chronic constriction injury, various behavioral tests (thermal hyperalgesia, cold allodynia) and biochemical parameters (lipid peroxidation, reduced glutathione, catalase, and nitrite) were assessed in sciatic nerves. Drugs were administered for 21 consecutive days from the day of surgery. CCI significantly caused thermal hyperalgesia, cold allodynia and oxidative damage. Chronic administration of melatonin (2.5 or 5 mg/kg, ip) significantly attenuated hyperalgesia, cold allodynia and oxidative damage in sciatic nerves as compared to CCI group. Further, L-NAME (5 mg/kg) pretreatment with sub-effective dose of melatonin (2.5 mg/kg, ip) significantly potentiated melatonin’s protective effect which was significant as compared to their individual effect per se. However, L-arginine (100 mg/kg) pretreatment with melatonin (2.5 mg/kg, ip) significantly reversed its protective effects. Results of the present study suggest the involvement of nitric oxide pathway in the protective effect of melatonin against CCI-induced behavioral and biochemical alterations in rats

Evaluation of bronchial inflammatory response via expression of NF-κB & IL-1β in mice airways by TAK-242 and LPS administration: Targeting TLR4/MD2 signalling pathway

Optimization of animal model of asthma via toll like receptors-4 (TLR4) activation for bacterial exacerbation of asthma. LPS contributes to asthma exacerbations. Ovalbumin protein sensitization &amp; challenge were examined after LPS exposure. Present research aimed, TLR4 stimulation mediated TLR4/MD2 complex formation is inhibited by TAK-242, a newer compound, for bacterial asthma management in a mouse model. Swiss Albino mice were induced with OVA (10µg, i.p. and 50 µg, i.n.) and LPS (20 µg, i.p. and 4 µg, i.n.), stimulates TLR4 receptor mediated TLR4-MD2 complex formation in toxic groups. Animals were sensitized (i.p.) on 0, 7th and 14th day and challenged (i.n.) followed by TAK-242 treatment (0.1 mg/kg, 1 mg/kg &amp;10 mg/kg i.p.) given on 21st and 22nd days, followed by euthanasia and samples; BALF and lung tissue were collected on 23rd day. Further analysis such as total leukocyte count &amp; differential leukocyte cell count, lung histopathology &amp; immunohistochemistry of NF-κB, proteins like Interleukin-1β in BALF and lungs in toxic, treatment groups in comparison with control group were carried out. TAK-242 reduced TLC/DLC values in BALF, including eosinophil, neutrophil, lymphocyte, macrophage counts, lung histological alterations and immunohistochemical positivity of NF-κB and IL-1β proteins expression.&nbsp