Pharmacological profile of agmatine: An in-depth overview.

Agmatine, a naturally occurring polyamine derived from arginine via arginine decarboxylase, has been shown to play multifaceted roles in the mammalian body, impacting a wide range of physiological and pathological processes. This comprehensive review delineates the significant insights into agmatine's pharmacological profile, emphasizing its structure and metabolism, neurotransmission and regulation, and pharmacokinetics and function. Agmatine's biosynthesis is highly conserved across species, highlighting its fundamental role in cellular functions. In the brain, comparable to established neurotransmitters, agmatine acts as a neuromodulator, influencing the regulation, metabolism, and reabsorption of neurotransmitters that are key to mood disorders, learning, cognition, and the management of anxiety and depression. Beyond its neuromodulatory functions, agmatine exhibits protective effects across various cellular and systemic contexts, including neuroprotection, nephroprotection, cardioprotection, and cytoprotection, suggesting a broad therapeutic potential. The review explores agmatine's interaction with multiple receptor systems, including NMDA, α2-adrenoceptors, and imidazoline receptors, elucidating its role in enhancing cell viability, neuronal protection, and synaptic plasticity. Such interactions underpin agmatine's potential in treating neurological diseases and mood disorders, among other conditions. Furthermore, agmatine's pharmacokinetics, including its absorption, distribution, metabolism, and excretion, are discussed, underlining the complexity of its action and the potential for therapeutic application. The safety and efficacy of agmatine supplementation, demonstrated through various animal and human studies, affirm its potential as a beneficial therapeutic agent. Conclusively, the diverse physiological and therapeutic effects of agmatine, spanning neurotransmission, protection against cellular damage, and modulation of various receptor pathways, position it as a promising candidate for further research and clinical application. This review underscores the imperative for continued exploration into agmatine's mechanisms of action and its potential in pharmacology and medicine, promising advances in the treatment of numerous conditions.

Identification of potential drug candidates to treat gastritis and associated oxidative stress based on some novel 2-aryl-1H-naphtho[2,3-d]imidazole: synthesis, in vitro and in silico analysis.

To identify potential scaffolds to treat gastritis and oxidative stress, 2-aryl-1H-naphtho[2,3-d]imidazole derivatives (1-15) were synthesized. The synthesis was conveniently carried out by condensing 2,3-diaminonaphthalene with variously substituted aldehydes to yield 15 new 2-aryl-1H-naphtho[2,3-d]imidazole derivatives. Structures of all synthesized compounds were elucidated using MS and NMR spectroscopic techniques. Compounds containing an imidazole moiety have continued to spark interest in the field of medicinal chemistry due to their unique properties. In continuation of this statement, to further explore the biological potential of these types of compounds, newly synthesized imidazole derivatives were evaluated for their inhibitory potential against urease and antioxidant activities. Compounds 4 and 11 were identified as the most potent urease inhibitors in the series, with IC50 values of 34.2 ± 0.72 and 42.43 ± 0.65 µM, respectively. Compounds 1, 3, 6, 11, and 15, with EC50 values in the range of 37-75 µg ml-1, showed significant antioxidant activity. Molecular docking studies of the selected synthesized compounds 3, 4, 9, and 11 were also performed to determine their binding interaction with the jack bean urease. Through docking studies, it was revealed that all the compounds that showed good inhibitory potential against urease fit well within the protein's binding pocket. Furthermore, ADME analysis was carried out to explore the drug-likeness properties of the compounds. The findings of the present work revealed that compounds 4 and 11 could be better options to treat gastritis and associated oxidative stress.

Natural remedies for Alzheimer's disease: A systematic review of randomized controlled trials.

Alzheimer's disease (AD) is the common type of dementia and is currently incurable. Existing FDA-approved AD drugs may not be effective for everyone, they cannot cure the disease nor stop its progression and their effects diminish over time. Therefore, the present review aimed to explore the role of natural alternatives in the treatment of AD. A systematic search was conducted using Ovid MEDLINE, CINAHL, Cochrane and PubMed databases and reference lists up to November 30, 2021. Only randomized control trials were included and appraised using the National Institute of Health framework. Data analysis showed that herbs like Gingko Biloba, Melissa Officinalis, Salvia officinalis, Ginseng and saffron alone or in combination with curcumin, low-fat diet, NuAD-Trail, and soy lecithin showed significant positive effects on AD. Moreover, combination of natural and pharmaceuticals has far better effects than only allopathic treatment. Thus, different herbal remedies in combination with FDA approved drugs are effective and more promising in treatment of AD.

Quercetin impact against psychological disturbances induced by fat rich diet.

Obesity is a metabolic disease which promotes by consuming fat rich diet. The consequences may include leptin resistant and initiation of metabolic syndromes. Beside the fact, obesity has psychological impacts it act as a signal of depression by stimulating endogenous stress stimulation. Quercetin is a natural polyphenol, considered as nutraceutical agent which produce antioxidant effects. It is reported to promote energy expenditure and protective mechanism against obesity. This presented work was designed to observe the effects of quercetin on high fat diet treated obese animals with impaired psychological behavior. The study comprised on 36 animals, divided in to different groups as follow: I Normal Diet and II. High fat diet. After the induction of obesity both groups divided in to further three subgroups as control, Quercetin and sertraline. Food intake and body weight along with behavioral analysis for four weeks were done for the assessment of anti-obesity and antidepressant effects of quercetin. The results showed the effective treatment of quercetin in obese animals, it significantly reduced the food intake and body weight of animals. The behavioral test showed the increased locomotor activity in the activity box and improved psychological behavior in quercetin-treated rats in the open field and light-dark box. It is concluded from the present study that quercetin exhibits the ameliorative effects against obesity and associated neuroendocrine alterations.

Ameliorative effects of half-dose saffron and chamomile combination on Psycho-endocrinological changes in a diabetic murine model.

INTRODUCTION: Diabetes mellitus is a chronic metabolic disorder with an increasing prevalence worldwide. Reduction in blood insulin level alters brain function by inducing oxidative stress with changes in dopamine and norepinephrine neurotransmission, ultimately leading to neuropsychological symptoms. The efficacy of currently available psychotropic drugs is not satisfactory. Therefore, this study was conducted to explore the beneficial effects of a combination of the natural herbs, saffron and chamomile, in treating diabetes and its resultant neuropsychological effects using a rodent model of diabetes mellitus. METHOD: The rats were randomly divided in to eight groups (n = 10), healthy control (HC), diabetic control (DC) and six groups of diabetic rats treated with various concentrations and combinations of saffron and chamomile. Diabetic treatment groups individually received methanolic extract and water decoction of chamomile (30 mg/kg) and saffron (10mg/kg) and their combined half doses (saffron 5mg/kg and chamomile 15mg/kg) for two weeks. Open field test (OFT) and forced swim test (FST) were used to measure the anxiolytic and antidepressant effects of herbs, respectively. Finally, biochemical, and neurochemical estimations were made. RESULTS: The present study suggests the therapeutic effects of herbs especially in co-administrated decoction, against diabetes with improved antioxidant profile and enhanced levels of dopamine and norepinephrine. Anxiolytic and antidepressant effects were evident with improvements in the OFT and FST. Examination of the cortex of the diabetic group revealed cellular damage and tangle formation, which indicates advanced stages of dementia. CONCLUSION: This study shows that the use of a combination of saffron and chamomile improves diabetes control and reduces its related psychiatric effects.

Inhibition of drug induced Parkinsonism by chronic supplementation of quercetin in haloperidol-treated wistars.

Haloperidol is a neuroleptic medication that is used to treat a wide range of neuropsychiatric conditions. It has been shown to produce medicinal effects against hyperactivity, agitation and mania, as well as schizophrenia. Long-term usage of haloperidol raises the risk of acquiring a neurological condition like Parkinson's disease. Haloperidol causes drug-induced Parkinsonism (DIP) by blocking central dopamine receptors and causing extrapyramidal symptoms during long-term treatment. Quercetin has been shown to reduce the loss of striatal neurons, which may enhance motor capabilities and protect against agents that cause the production of reactive oxygen species (ROS). As a result, present study intended to evaluate the efficacy of quercetin on haloperidol-related motor abnormalities. To develop behavioral impairments, rats (n=24) randomly divided to control and haloperidol group for four weeks. The animals were split into four groups after four weeks: Control, quercetin, haloperidol and haloperidol + quercetin. Animals were administered haloperidol i.p injections of 5mg/kg and quercetin (100mg/kg) orally for 21 days. The treatment of haloperidol-treated rats with quercetin was successful in reversing the haloperidol alterations. It decreased animal food intake and alleviated anxiogenic behavior. The chronic treatment of quercetin further reduced the movement abnormalities in animal model of drug induced pseudo-Parkinson.

Comparative Effectiveness of Agmatine and Choline Treatment in Rats with Cognitive Impairment Induced by AlCl3 and Forced Swim Stress.

AIM: Endogenous agmatine has a significant role in learning and memory processes as a neurotransmitter. Various studies described the physiological role of endogenous agmatine in learning and memory of multiple cognitive tasks suggesting elevated levels of agmatine during the learning process in the rat brain. Dietary intake of choline showed correlation with cognitive functions in human subjects and treatment with choline supplements validated the ability to diminish learning and cognitive impairment dementias. METHODS: 36 Albino rats were equally divided into three groups previously: a) control-water, b) Test I - AlCl3 (100 mg/Kg body weight), and c) Test II - Forced swim stress (FSS) for 14 days. On the next day of AlCl3 and FSS last administration, animals were allocated into further three groups and received the following treatments: a. water was given orally to the control group, b. Agmatine (100 mg/Kg Body Weight) group, and c. Choline (100 mg/Kg Body Weight) group for the next 14 days. Behaviors were assessed in Light/Dark Box, Open Field, Novel Object Recognition Test (NOR), T Maze Test, and Morris Water Maze Test. RESULTS: Animals administered with agmatine demonstrated increased time spent in bright areas of light/dark box and square crossed while improved spatial memory in Morris water maze and T maze test and enhanced discrimination of novel object in NOR were observed in learning and memory paradigms along with choline. CONCLUSION: The present study determines that agmatine at the dose of (100 mg/kg body weight) attenuates memory and cognitive impairment in comparison with choline supplements.

Desensitization of 5-HT-1A Somatodentritic Receptors in Tryptophan Treated and Co-treated Rats Induced by Methylphenidate.

BACKGROUND: Psychostimulants can induce behavioral sensitization by their chronic use. The main target for the action of these drugs is dopamine, neither epinephrine nor serotonin transporters. Serotonin is synthesized by the precursor L-tryptophan. Tryptophan and methylphenidate being 5-HT agonists, both increase the level of serotonin thereby causing desensitization of 5-HT1a receptors. The present study investigated whether behavioral sensitization induced by Methylphenidate is decreased in tryptophan administrated animals. METHODS: The Experiment was divided into 2 phases (1). Behavioral effects of repeated administration of TRP 100 mg/kg and MPD for 14 days in three groups; (i) water (ii) MPD 1.0 mg/kg (iii) TRP. To explore the locomotor effects of treatment, the activity was monitored in a familiar and novel environment. (2) Behavioral consequences of repeatedly administrated MPD (1.0 mg/kg) on pretreated TRP (100 mg/kg) and MPD (1.0 mg/kg) animals following Co-MPD and TRP for 14 days, rats were divided in three groups (i) water, (ii) MPD and (iii) TRP as mentioned in Experiment no 1. After two weeks six subgroups were assigned i.e. (i) water-saline, (ii) water- MPD, (iii) TRP-saline (iv) TRP-MPD (v) MPD-saline and (vi) MPD-MPD+TRP and treated for further 14 days. Locomotor behavior was monitored in familiar environment on the next day and in novel environment on alternate days of each administration. RESULTS: The Results from phase 1 showed increased activity in both (TRP and MPD) treatments. However, the results of phase 2 showed significant decrease in methylphenidate-induced behavioral sensitization by both pretreatment and co-administration with TRP. CONCLUSION: The present study suggests the potential of tryptophan to decrease the risk of behavioral sensitization induced by methylphenidate.