RESUMO
BACKGROUND: Withania somnifera (WS), a popular medicinal plant of the Solanaceae family, contains active ingredients with antioxidant, anti-inflammatory, immunomodulatory, and anti-stress activities. However, its precise mechanisms of action and optimal use as a supplement are not yet fully understood. The objective of this systematic review is to assess the impact of WS supplementation on cortisol levels in stressed humans by analyzing clinical trials conducted prior to May 2023. METHODS: The assessment was carried out following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) by exploring the databases of EMBASE, PubMed, Google Scholar, CENTRAL, and Scopus. RESULTS: Of the 4788 articles identified, only 9 studies met the selection criteria. The selected studies varied in terms of design, results, formulations, dosages, and treatment duration (30-112 days), and involved subjects with varying degrees of stress. WS supplementation decreases cortisol secretion with no significant adverse effects. Nonetheless, none of the studies evaluated the potential impact of cortisol reduction on adrenal function and long-term effects. CONCLUSIONS: Brief-term supplementation with WS appears to have a stress-reducing effect in stressed individuals. However, since the long-term effects of WS supplementation are not yet fully understood, WS supplements should be used under medical supervision.
Assuntos
Plantas Medicinais , Withania , Humanos , Extratos Vegetais/uso terapêutico , Hidrocortisona , Antioxidantes/farmacologiaRESUMO
PURPOSE: In less than one and a half year, the COVID-19 pandemic has nearly brought to a collapse our health care and economic systems. The scientific research community has concentrated all possible efforts to understand the pathogenesis of this complex disease, and several groups have recently emphasized recommendations for nutritional support in COVID-19 patients. In this scoping review, we aim at encouraging a deeper appreciation of magnesium in clinical nutrition, in view of the vital role of magnesium and the numerous links between the pathophysiology of SARS-CoV-2 infection and magnesium-dependent functions. METHODS: By searching PubMed and Google Scholar from 1990 to date, we review existing evidence from experimental and clinical studies on the role of magnesium in chronic non-communicable diseases and infectious diseases, and we focus on recent reports of alterations of magnesium homeostasis in COVID-19 patients and their association with disease outcomes. Importantly, we conduct a census on ongoing clinical trials specifically dedicated to disclosing the role of magnesium in COVID-19. RESULTS: Despite many methodological limitations, existing data seem to corroborate an association between deranged magnesium homeostasis and COVID-19, and call for further and better studies to explore the prophylactic or therapeutic potential of magnesium supplementation. CONCLUSION: We propose to reconsider the relevance of magnesium, frequently overlooked in clinical practice. Therefore, magnesemia should be monitored and, in case of imbalanced magnesium homeostasis, an appropriate nutritional regimen or supplementation might contribute to protect against SARS-CoV-2 infection, reduce severity of COVID-19 symptoms and facilitate the recovery after the acute phase.
Assuntos
COVID-19 , Homeostase , Humanos , Magnésio , Pandemias , SARS-CoV-2Assuntos
COVID-19/epidemiologia , Deficiência de Magnésio/epidemiologia , Magnésio/fisiologia , Envelhecimento , COVID-19/prevenção & controle , Doenças Cardiovasculares/epidemiologia , Comorbidade , Congressos como Assunto , Suscetibilidade a Doenças , Humanos , Sistema Imunitário/fisiologia , Inflamação/epidemiologia , Deficiência de Magnésio/terapia , Doenças Metabólicas/epidemiologia , Neoplasias/epidemiologia , Obesidade/epidemiologia , Pesquisa , Sociedades CientíficasRESUMO
Magnesium (Mg2+) deficiency is probably the most underestimated electrolyte imbalance in Western countries. It is frequent in obese patients, subjects with type-2 diabetes and metabolic syndrome, both in adulthood and in childhood. This narrative review aims to offer insights into the pathophysiological mechanisms linking Mg2+ deficiency with obesity and the risk of developing metabolic syndrome and type 2 diabetes. Literature highlights critical issues about the treatment of Mg2+ deficiency, such as the lack of a clear definition of Mg2+ nutritional status, the use of different Mg2+ salts and dosage and the different duration of the Mg2+ supplementation. Despite the lack of agreement, an appropriate dietary pattern, including the right intake of Mg2+, improves metabolic syndrome by reducing blood pressure, hyperglycemia, and hypertriglyceridemia. This occurs through the modulation of gene expression and proteomic profile as well as through a positive influence on the composition of the intestinal microbiota and the metabolism of vitamins B1 and D.
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Microbioma Gastrointestinal , Magnésio/administração & dosagem , Síndrome Metabólica/metabolismo , Obesidade/metabolismo , Adulto , Criança , Diabetes Mellitus Tipo 2/tratamento farmacológico , Suplementos Nutricionais , Humanos , Deficiência de Magnésio/tratamento farmacológico , Síndrome Metabólica/tratamento farmacológico , Proteômica , Tiamina/metabolismo , Vitamina D/metabolismoRESUMO
Magnesium deficiency may occur for several reasons, such as inadequate intake or increased gastrointestinal or renal loss. A large body of literature suggests a relationship between magnesium deficiency and mild and moderate tension-type headaches and migraines. A number of double-blind randomized placebo-controlled trials have shown that magnesium is efficacious in relieving headaches and have led to the recommendation of oral magnesium for headache relief in several national and international guidelines. Among several magnesium salts available to treat magnesium deficiency, magnesium pidolate may have high bioavailability and good penetration at the intracellular level. Here, we discuss the cellular and molecular effects of magnesium deficiency in the brain and the clinical evidence supporting the use of magnesium for the treatment of headaches and migraines.
Assuntos
Cefaleia/tratamento farmacológico , Magnésio/farmacocinética , Transtornos de Enxaqueca/tratamento farmacológico , Ácido Pirrolidonocarboxílico/farmacocinética , Administração Oral , Disponibilidade Biológica , Suplementos Nutricionais , Humanos , Magnésio/uso terapêutico , Deficiência de Magnésio/tratamento farmacológico , Ácido Pirrolidonocarboxílico/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
N6-isopentenyladenosine is an anti-proliferative and pro-apoptotic atypical nucleoside for normal and tumor cells. Considering the role of angiogenesis in various diseases, we investigated the cytotoxic effect of N6-isopentenyladenosine on human microvascular endothelial cells, protagonists in angiogenesis. Our results show that N6-isopentenyladenosine induced a significant reduction of cell viability, upregulated p21 and promoted caspase-3 cleavage in a dose dependent manner leading to apoptotic cell death as detected by FACS analysis. To understand structure-function relationship of N6-isopentenyladenosine, we investigated the effect of some N6-isopentenyladenosine analogs. Our results suggest that N6-isopentenyladenosine and some of its derivatives are potentially novel angiostatic agents and might be associated with other anti-angiogenic compounds for a better outcome.
Assuntos
Inibidores da Angiogênese/farmacologia , Endotélio Vascular/citologia , Isopenteniladenosina/farmacologia , Inibidores da Angiogênese/administração & dosagem , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Células Endoteliais/efeitos dos fármacos , Humanos , Interferon gama/farmacologia , Isopenteniladenosina/administração & dosagemRESUMO
A tight control of magnesium homeostasis seems to be crucial for bone health. On the basis of experimental and epidemiological studies, both low and high magnesium have harmful effects on the bones. Magnesium deficiency contributes to osteoporosis directly by acting on crystal formation and on bone cells and indirectly by impacting on the secretion and the activity of parathyroid hormone and by promoting low grade inflammation. Less is known about the mechanisms responsible for the mineralization defects observed when magnesium is elevated. Overall, controlling and maintaining magnesium homeostasis represents a helpful intervention to maintain bone integrity.
Assuntos
Suplementos Nutricionais , Magnésio/administração & dosagem , Osteoporose/tratamento farmacológico , Osteoporose/prevenção & controle , Animais , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Modelos Animais de Doenças , Homeostase , Humanos , Deficiência de Magnésio/complicações , Deficiência de Magnésio/tratamento farmacológico , Osteoporose/complicações , Hormônio Paratireóideo/metabolismoRESUMO
Over recent decades there have been several papers that documented hypomagnesaemia*, in cancer patients treated, with cisplatin, with combined chemotherapies and more recently, with cetuximab an antibody against the epidermal growth factor receptor. Recently, however, the clinical read-out of cetuximab-induced hypomagnesaemia has received different interpretations. Some reports called the readers' attention to the importance of magnesium supplementation in relieving patient's discomfort or preventing the most severe complications of hypomagnesaemia. Other reports claimed that magnesium deficiency could contribute to the oncologic efficacy of cetuximab. This latter interpretation implies that the decision on magnesium supplementation should consider the pros and cons of returning magnesium to normal levels. Given that decreased magnesium availability inhibits cell proliferation, hypomagnesaemia may slow down tumor growth. Unfortunately, one view does not fit all. We think it important to recapitulate our knowledge on the effects of magnesium on tumor growth, angiogenesis, invasion and metastatization with the aim of providing clinical oncologists with an overview of available data of the potential effects of hypomagnesaemia in tumor growth. Translating these results into clinical settings may help in designing suitable studies to better evaluate the consequences of hypomagnesaemia in cancer patients.
Assuntos
Antineoplásicos/efeitos adversos , Deficiência de Magnésio/induzido quimicamente , Magnésio/sangue , Neoplasias/sangue , Animais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Cetuximab , Humanos , Deficiência de Magnésio/tratamento farmacológico , Neoplasias/tratamento farmacológicoRESUMO
We have previously shown that a low Magnesium (Mg)-containing diet reversibly inhibits the growth of primary tumors that develop after the injection of Lewis lung carcinoma (LLC) cells in mice. Here we investigate some of the mechanisms responsible for the Mg-dependent regulation of tumor development by studying cell cycle regulation, tumor angiogenesis, and gene expression under Mg deficiency. The inhibition of LLC tumor growth in Mg-deficient mice is due to a direct effect of low Mg on LLC cell proliferation and to an impairment of the angiogenic switch. We also observed an increase of nitric oxide synthesis and oxidative DNA damage. Complementary DNA arrays reveal that Mg deficiency modulates tumor expression of genes involved in the control of cell cycle, stress response, proteolysis, and adhesion. Our results suggest that Mg has multiple and complex roles in tumor development.
Assuntos
Carcinoma Pulmonar de Lewis/metabolismo , Ciclo Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Deficiência de Magnésio/metabolismo , Magnésio/farmacologia , Neoplasias Experimentais/metabolismo , Animais , Western Blotting , Carcinoma Pulmonar de Lewis/patologia , Proliferação de Células/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , DNA de Neoplasias/análise , Feminino , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genes Neoplásicos , Humanos , Magnésio/sangue , Magnésio/metabolismo , Deficiência de Magnésio/patologia , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Experimentais/patologia , Óxido Nítrico Sintase/metabolismo , Análise de Sequência com Séries de OligonucleotídeosRESUMO
Magnesium supplementation has been reported to prevent cardiovascular diseases through the decrease of plasma lipids and to improve endothelial function in patients with coronary artery disease. In the present work, we evaluated whether high magnesium concentrations can directly affect the function of cultured endothelial cells, which play a crucial role in maintaining the functional integrity of the vascular wall. We cultured human umbilical vein endothelial cells for various times in media containing different concentration of magnesium (range 2 to 10 mM) and compared them to the corresponding controls (1 mM Mg). High Mg concentrations stimulated endothelial proliferation, enhanced the motogenic response to angiogenic factors and attenuated the response to lipopolysaccharide (LPS). In addition, we demonstrate that high concentrations of magnesium did not modulate the levels of plasminogen activator inhibitor-1, but enhanced the synthesis of nitric oxide, in part through the up-regulation of endothelial nitric oxide synthase. Our results demonstrate a direct role of magnesium in maintaining endothelial function. We therefore anticipate that magnesium may have a protective effect against atherosclerosis and could play a role in promoting the growth of collateral vessels in chronic ischemia. Moreover, because it induces the synthesis of nitric oxide, this cation could be a helpful tool in hypertension as well as in preventing thrombosis.
Assuntos
Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Magnésio/farmacologia , Adesão Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Endotélio Vascular/enzimologia , Humanos , Óxido Nítrico Sintase/metabolismo , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Trombose/patologiaRESUMO
Several data indicate that magnesium deficiency caused by poor diet and/or errors in its metabolism may be a missing link between diverse cardiovascular risk factors and atherosclerosis. Experimentally induced low plasma levels of magnesium accelerate atherogenesis by increasing LDL concentrations and their oxidative modifications, and by promoting inflammation. In vitro studies have shown that low magnesium determines endothelial dysfunction, the initiating event leading to the formation of the plaque. Moreover, oral magnesium therapy has been shown to improve endothelial function in patients with coronary artery disease.Magnesium, which is an inexpensive, natural and rather safe element, could be useful in preventing atherosclerosis and as an adjuvant therapy in patients with clinical manifestations of the disease.