RESUMO
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.
Assuntos
Agmatina , Agmatina/farmacologia , Agmatina/metabolismo , Humanos , Animais , Fármacos Neuroprotetores/farmacologia , Neurotransmissores/metabolismo , Neurotransmissores/farmacologia , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Receptores de Imidazolinas/metabolismoRESUMO
Myocardial infarction (MI) is a leading cause of morbidity and mortality in the world and is characterized by ischemic necrosis of an area of the myocardium permanently devoid of blood supply. During reperfusion, reactive oxygen species are released and this causes further insult to the myocardium, resulting in ischemia-reperfusion (IR) injury. Since Nrf2 is a key regulator of redox balance, it is essential to determine its contribution to these two disease processes. Conventionally Nrf2 levels have been shown to rise immediately after ischemia and reperfusion but its contribution to disease process a week after the injury remains uncertain. Mice were divided into MI, IR injury, and sham surgery groups and were sacrificed 1 week after surgery. Infarct was visualized using H&E and trichrome staining and expression of Nrf2 was assessed using immunohistochemistry, Western blot, and ELISA. MI displayed a higher infarct size than the IR group (MI: 31.02 ± 1.45%, IR: 13.03 ± 2.57%; p < 0.01). We observed a significantly higher expression of Nrf2 in the MI group compared to the IR model using immunohistochemistry, spot densitometry of Western blot (MI: 2.22 ± 0.16, IR: 1.81 ± 0.10, Sham: 1.52 ± 0.13; p = 0.001) and ELISA (MI: 80.78 ± 27.08, IR: 31.97 ± 4.35; p < 0.01). There is a significantly higher expression of Nrf2 in MI compared to the IR injury group. Modulation of Nrf2 could be a potential target for therapeutics in the future, and its role in cardioprotection can be further investigated.
Assuntos
Infarto do Miocárdio , Traumatismo por Reperfusão Miocárdica , Animais , Camundongos , Isquemia , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Regulação para CimaRESUMO
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.
Assuntos
Síndrome Metabólica , Quercetina , Animais , Ratos , Quercetina/farmacologia , Dieta Hiperlipídica/efeitos adversos , Obesidade , Peso CorporalRESUMO
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.
Assuntos
Antipsicóticos , Doença de Parkinson , Ratos , Animais , Haloperidol/toxicidade , Quercetina/farmacologia , Antipsicóticos/efeitos adversos , Doença de Parkinson/tratamento farmacológico , Suplementos NutricionaisRESUMO
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.