Current Psychopharmacology - Volume 7, Issue 2, 2018

Insulin Resistance (IR) is a physiological condition in which pancreatic cells fail to respond to normal actions of insulin hormone. It is a milestone for the development of diabetes and its complications. The current approach for the treatment of the diabetes and insulin resistance includes pharmacotherapeutics. However, this therapy includes the development of drug tolerance, potential toxicity and inadequate relief warranting the investigation of newer approaches for treatment. A potentially safe and effective therapeutic treatment for insulin resistance (IR) in diabetes is required. The current research is focused on herbal or phytochemical drugs. The potential herbal targets with insulin mimetic, secretagogues and promising activity are under the scope of this review. In this review, we have discussed the herbal targets and non-pharmacological approaches for the treatment of IR in diabetes. This review aims to compile the relevant information regarding various phases of drug development for the management of the insulin resistance and highlight the future prospective for its treatment by natural and semi-synthetic drugs.

Background: Diabetes and its associated complications like nephropathy and neuropathy have been identified as a worldwide problem. The epidemiological data revealed that there is up to 60% of patients suffering from diabetic peripheral neuropathy (DPN) which is associated with significant morbidity, including gait disturbances, amputations, anxiety and depression. The various dietary interventions play a significant role in the prevention of these chronic ailments. The therapeutic investigation of new dietary interventions for the management of diabetes and their related complications are evidently proved by numerous animal and human studies which further help in translating these nutritional improvements for the betterment of healthcare system. Objective: Various scientific researches demonstrate that dietary therapy and their interventions prove to be beneficial and therapeutic for the management of diabetes and their associated chronic complications. The aim of this review is to describe the various aspects of diet restriction or diet therapy for the management of diabetic neuropathy and nephropathy. Method: The systematic bibliographical research was done with the help of PubMed, Google scholar and MedLine literature survey to identify all suitable association between diet restriction and diet therapy with diabetic neuropathy and nephropathy. Results: Our searches yielded approximately 180 appropriate citations, from which we included 35 relevant scientific pieces of evidence in the present review. Conclusion: It is clearly stated that inappropriate and unbalanced dietary habits cause devastating effects on the progression of diabetes and associated complications. However, dietary supplementations and interventions act by normalizing the nerve conduction velocity, brain oxidative stress and by repairing the damaged neuronal cells and maintain the normal conduction pathways of the brain. The focus of the current review is on the various preclinical evidences with reference to various dietary modifications for the management of diabetic neuropathy & nephropathy. Still, there is a need to explore new insight mechanisms of dietary supplements for the treatment of diabetes-associated complications of human health.

Background: Epilepsy is a neurological disorder manifested by recurrent episodes of seizures, loss of consciousness, and sensory disturbances. Epileptic seizure is generated due to functional disturbance within the population of neurons. The present study was conducted to evaluate the effect of various classical neurotransmitter and neuropeptides in epilepsy in humans as well as in rodents. Objectives: The present study reviews the role of various brain neurotransmitters viz. GABA, glutamate, biogenic amines, and neuropeptides in the prevention and regulation of epileptic seizure in humans as well as in various animal models of epilepsy. Discussion: We provide evidences, from various clinical and pre-clinical studies, regarding role of individual brain neurotransmitters in the pathophysiology of Epilepsy. Gamma Aminobutyric Acid (GABA) hypoactivity induces dopamine hyperactivity as dopaminergic neurons are affected by the inhibitory influence of the GABAergic system through GABA (A) receptors. Glutamate hyperactivity is exerted via presynaptic N-methyl-D-aspartate (NMDA) receptors and postsynaptic ionotropic glutaminergic receptors that strongly inhibit serotoninergic neurons and induce epileptic seizures, respectively. This study suggests that there is an increase in the electrical activity of cortex on topical application of Ach following the administration of pentylenetetrazole. However, the neuropeptides like substance increase the glutamate-dependent excitotoxicity by acting on the NK1 receptors. The study also suggests the involvement of nitric oxide mechanism in epilepsy by over-activation of NMDA receptors. The endocannabinoids, such as Cannabinoids produce neuroprotective effects by antagonistic action on NMDA receptors and inverse agonism on CB1 receptors. However, the chronic overexpression of Adenosine Kinase (ADK) causes seizures in epilepsy. The anticonvulsant actions of adenosine are mainly mediated via activation of A1 receptors. Conclusion: Thus, the present review suggests a possible involvement of neurotransmitter and neuropeptides in epilepsy in humans and rodents.

Mental illnesses are affecting several millions of individuals in the U.S and worldwide. Statistics have revealed that one among six adults in the United States is suffering from a mental illness with varying severity. Accordingly, mental illnesses are considered as one of the major factors behind the global disability as well as health and economic burden. The conventional treatments prescribed to treat mood and mental disorders are observed to show a response in only 30-40% of patients with major depression disorder (MDD). Besides, the serious adverse events associated with these treatments have also made it urgent for scientists and researchers to search for other alternatives to be used as monotherapies or adjuvants to conventional treatments. In this review, we have summarized a number of the most extensively-studied natural remedies indicated for the treatment of anxiety and depression. We have also included some of the common nutraceuticals used to treat both anxiety and depression, along with a number of the newly-emerged adjuvant therapies.

Background: Diverse chronic disease arises with aging including cardiac and neurodegenerative disorders. Oxidative stress is considered to be the important cause of aging which can affect various vital organs and lead to a general reduction in physiological functions. The brain is the most sensitive organ towards such oxidative stress due to high oxygen consumption and higher metabolism. Aging of the brain can impair the cognitive skills and memory which lead to the demented condition. The histopathological hallmarks of dementia are a neuronal loss in the forebrain, generation of amyloid β plaque and neurofibrillary tangles. It eventually abolishes the thinking skill and memory. Objective: Thus, dementia is a major public health concern, with economic and social burden, of which occurrence is greatly increasing. There is no cure for dementia, however, only a few approved drugs are available for the management of the demented condition. Hence, there is a need of alternative medicine for effective treatment and management. Method: Nowadays, several herbal products have been introduced with their neuroprotective effects, with additional advantages of being low cost, easily available and with fewer side effects. Conclusion: This review represented the pathophysiology of dementia, classification with current therapy and advancement in plant products for their potential neuroprotective properties.

Lycopene is a carotenoid that is mainly found in tomatoes products and other fruits. Out of all the dietary carotenoids, it is the most potent carotenoid quenchers of singlet oxygen. Literature suggested that dietary intake of tomatoes and tomato products containing Lycopene has been associated with a decreased risk of chronic diseases. Lycopene is also reported to be a potent hypocholesterolemic agent, antiatherosclerotic, and anti-cancerous. It is useful in the treatment of osteoporosis, dermatology and dental hygiene. It also exhibits antiinflammatory and anticoagulant activity. The antioxidant property of Lycopene is thought to be primarily responsible for its beneficial effects. This review showed the understanding and possible pharmacological action of Lycopene in human health and disease prevention.

Backgroud: Walnut appears as the Signature of the Head and the kernel looks alike as the brain. It is a traditional belief that Walnuts may be beneficial to the brain. Objective: In the light of this traditional belief, the present study was conducted to confirm the effects of Juglan regia (Walnut) on cognitive functions of mice. Method: Two doses (500, 1000 mg/kg) of Walnut kernel powder were administered along with diet for fourteen successive days to Swiss young and aged mice. 29 groups of 145 Swiss young mice and 13 groups of 65 aged mice were employed in the present study. Exteroceptive behavioral models used in the present study were elevated plus maze and passive avoidance apparatus. Results: Decreased TL and increased SDL values were indicative of a significant improvement in the memory of young and aged mice after Walnut powder administration. It also reversed the memory deficits induced by scopolamine and diazepam. In addition, the brain cholinesterase activity in young and aged mice was significantly inhibited by Walnut at the dose of 500 mg/kg. Walnut also showed a notable reduction in total cholesterol levels to the limit of 20% in young and 14% in aged mice at the dose of 500 mg/kg. Enhanced acetylcholine levels resulting from diminished AChE activity and hypocholesterolemia produced by Walnut appear to be the underlying mechanism for the improved memory of mice.

Background: Acute withdrawal symptoms in nicotine user predispose them to relapse during cessation attempts and pose difficulty in treatment of nicotine addiction. The present study was undertaken to explore the behavioral effects of azelnidipine in nicotine withdrawal model of mouse. Method: Swiss albino mice (either sex; 20-25 g) were administrated with nicotine (3.35 mg/kg; s.c.) three times daily for seven days. Nicotine withdrawal was developed by the cessation of nicotine administration and the abstinence signs (rearing, grooming, head shake, jumping, leg licking and genital licking) were observed for 30 min on ninth day. Azelnidipine was administered (6, 9 and 12 mg/kg; p.o.) for seven days to separate groups of mice from 9th to 15th day of nicotine administration. On 15th day, the behavioral studies were carried out to investigate anxiety, memory and depression like behavior, respectively. Afterwards, brain thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) levels and catalase activity were estimated. Results: Nicotine abstinent mice showed marked (p < 0.05) signs of anxiety, impaired memory and depression-like symptoms. Nicotine abstinent mice showed increase (p < 0.05) in TBARS levels, decrease in GSH levels and catalase activity. However, azelnidipine administration not only decreased (p < 0.05) abstinence signs but also improved the behavioral scores of animals. Furthermore, AZD administration caused reduction in TBARS levels and enhancement in GSH levels and catalase activity. Conclusion: Azelnidipine proves effective in the management of nicotine withdrawal symptoms owing to its calcium channel antagonistic and antioxidant properties.

Background: Traumatic brain injury (TBI) is the leading cause of death and disability among children and young adults worldwide. The 5-HT2C and melatonin receptors are known to have involvement in memory functions. Objective: To find the beneficial effect of agomelatine against weight drop induced TBI in rats. Method: The weight-drop model closely mimics the real-life TBI. The injury was induced by dropping a weight of 450 gm from a height of 1 meter through a hollow metallic tube onto the exposed skull of rats under anesthesia. After 14 days of TBI, the agomelatine (10, 20, and 40 mg/kg p.o. daily) treatment was given for next 14 days (i.e. until 28th day). The cognitive impairment was observed in Morris water maze (from 24th to 28th day) and novel object recognition (on 27th and 28th day) test. Immediately after behavioral parameters, animals were sacrificed and hippocampus and cortex were isolated for biochemical, neuroinflammatory and neurochemical estimation. Results: The weight drop model significantly induced memory impairment in TBI rats that has been assessed by Morris water maze and object recognition task. A significant rise in acetylcholinesterase activity, neuroinflammatory markers, oxidative stress was found in both cortex and hippocampal regions of traumatized rat brain. While agomelatine (10, 20, and 40 mg/kg p.o.) treated rats have shown memory enhancing effects dose-dependently, as compared to TBI control rats in Morris water maze as well as novel object recognition test. Further, agomelatine treated rats have shown a significant increase in serotonin, dopamine and norepinephrine levels in TBI rat brain. Conclusion: Agomelatine treated rats have been shown to alter the cognitive deficit due to TBI by enhancing the memory as shown in Morris water maze and object recognition test, as well as a substantial rise in neurotransmitters, suggesting that agomelatine may possess memory-enhancing effects. Hence, we deduce that agomelatine may represent a promising new neuroprotective drug for cognitive enhancing effects in TBI.

Aim: The aim of the present study was to evaluate the protective effect of ferulic acid in monosodium glutamate-induced anxiety and motor incoordination. Method: Laca BALB/c mice of either sex were treated intraperitoneally with test drug:Ferulic acid (100 & 200 mg/kg), inducer: Monosodium glutamate (100mg/kg) along with Diazepam (2 mg/kg) intraperitoneally as a standard anxiolytic drug and then exposed to Elevated plus maze, Hole board and Mirror chamber models. Results: The test drug shows a significant reduction in motor activity and enhances the open arm exploratory time in elevated plus maze model. This drug increases the number of head dips in hole board model. It also enhances the number of entries and time spent in the mirror chamber. All of the changes were highly significant. Conclusion: The present study concludes that Ferulic acid shows significant anxiolytic activity at the dose of 100 and 200 mg/kg against monosodium glutamate-induced anxiety and motor incoordination.