Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 16 de 16
Filtrar
Mais filtros








Base de dados
Intervalo de ano de publicação
1.
J Nutr Metab ; 2024: 6252426, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38883868

RESUMO

Lycopene is a naturally occurring carotenoid predominantly found in tomatoes and tomato-based products. Like other phytochemicals, it exhibits health beneficial biological activities that can be exploited when it is used as a dietary supplement. In vitro and in vivo, lycopene has been demonstrated to mitigate oxidative stress-induced metabolic dysfunctions and diseases including inflammation, obesity, and diabetes mellitus. Lycopene has been shown to alleviate metabolic diseases that affect the bone, eye, kidney, liver, lungs, heart, and nervous system. This review presents the state of the art regarding lycopene's health benefits and its potential applications in health system delivery. Furthermore, lycopene's protective effects against toxins, safety in its use, and possible toxicity are explored.

2.
Cell Biochem Funct ; 42(2): e3950, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38348768

RESUMO

Melanoma, an invasive class of skin cancer, originates from mutations in melanocytes, the pigment-producing cells. Globally, approximately 132,000 new cases are reported each year, and in South Africa, the incidence stands at 2.7 per 100,000 people, signifying a worrisome surge in melanoma rates. Therefore, there is a need to explore treatment modalities that will target melanoma's signalling pathways. Melanoma metastasis is aided by ligand activity of transforming growth factor-beta 1 (TGF-ß1), vascular endothelial growth factor-C (VEGF-C) and C-X-C chemokine ligand 12 (CXCL12) which bind to their receptors and promote tumour cell survival, lymphangiogenesis and chemotaxis. (3-(4-dimethylaminonaphthelen-1-ylmethylene)-1,3-dihydroindol-2-one) MAZ-51 is an indolinone-based molecule that inhibits VEGF-C induced phosphorylation of vascular endothelial growth factor receptor 3 (VEGFR-3). Despite the successful use of conventional cancer therapies, patients endure adverse side effects and cancer drug resistance. Moreover, conventional therapies are toxic to the environment and caregivers. The use of medicinal plants and their phytochemical constituents in cancer treatment strategies has become more widespread because of the rise in drug resistance and the development of unfavourable side effects. Zingerone, a phytochemical derived from ginger exhibits various pharmacological properties positioning it as a promising candidate for cancer treatment. This review provides an overview of melanoma biology and the intracellular signalling pathways promoting cell survival, proliferation and adhesion. There is a need to align health and environmental objectives within sustainable development goals 3 (good health and well-being), 13 (climate action) and 15 (life on land) to promote early detection of skin cancer, enhance sun-safe practices, mitigation of environmental factors and advancing the preservation of biodiversity, including medicinal plants. Thus, this review discusses the impact of cytostatic cancer drugs on patients and the environment and examines the potential use of phytochemicals as adjuvant therapy.


Assuntos
Guaiacol/análogos & derivados , Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/metabolismo , Fator C de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular , Ligantes , Desenvolvimento Sustentável , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Compostos Fitoquímicos
3.
Math Med Biol ; 40(3): 266-290, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37669569

RESUMO

Inhibiting a signalling pathway concerns controlling the cellular processes of a cancer cell's viability, cell division and death. Assay protocols created to see if the molecular structures of the drugs being tested have the desired inhibition qualities often show great variability across experiments, and it is imperative to diminish the effects of such variability while inferences are drawn. In this paper, we propose the study of experimental data through the lenses of a mathematical model depicting the inhibition mechanism and the activation-inhibition dynamics. The method is exemplified through assay data obtained from an experimental study of the inhibition of the chemokine receptor 4 (CXCR4) and chemokine ligand 12 (CXCL12) signalling pathway of melanoma cells. The quantitative analysis is conducted as a two step process: (i) deriving theoretically from the model the cell viability as a function of time depending on several parameters; (ii) estimating the values of the parameters by using the experimental data. The cell viability is obtained as a function of concentration of the inhibitor and time, thus providing a comprehensive characterization of the potential therapeutic effect of the considered inhibitor, e.g. $IC_{50}$ can be computed for any time point.


Assuntos
Neoplasias , Transdução de Sinais , Linhagem Celular Tumoral , Receptores CXCR4/metabolismo , Quimiocina CXCL12/metabolismo , Quimiocina CXCL12/farmacologia , Neoplasias/tratamento farmacológico
4.
Metabolites ; 13(2)2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36837786

RESUMO

Alcohol intake at different developmental stages can lead to the development of alcohol-induced fatty liver disease (AFLD). Zingerone (ZO) possess hepato-protective properties; thus, when administered neonatally, it could render protection against AFLD. This study aimed to evaluate the potential long-term protective effect of ZO against the development of AFLD. One hundred and twenty-three 10-day-old Sprague-Dawley rat pups (60 males; 63 females) were randomly assigned to four groups and orally administered the following treatment regimens daily during the pre-weaning period from postnatal day (PND) 12-21: group 1-nutritive milk (NM), group 2-NM +1 g/kg ethanol (Eth), group 3-NM + 40 mg/kg ZO, group 4-NM + Eth +ZO. From PND 46-100, each group from the neonatal stage was divided into two; subgroup I had tap water and subgroup II had ethanol solution as drinking fluid, respectively, for eight weeks. Mean daily ethanol intake, which ranged from 10 to 14.5 g/kg body mass/day, resulted in significant CYP2E1 elevation (p < 0.05). Both late single hit and double hit with alcohol increased liver fat content, caused hepatic macrosteatosis, dysregulated mRNA expression of SREBP1c and PPAR-α in male and female rats (p < 0.05). However, neonatal orally administered ZO protected against liver lipid accretion and SREBP1c upregulation in male rats only and attenuated the alcohol-induced hepatic PPAR-α downregulation and macrosteatosis in both sexes. This data suggests that neonatal orally administered zingerone can be a potential prophylactic agent against the development of AFLD.

5.
Drug Chem Toxicol ; 46(4): 736-745, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35734876

RESUMO

Neonatal alcohol exposure (NAE) can induce oxidative stress. We determined whether zingerone (ZO), a phytochemical with anti-oxidant activity, can mitigate the negative impact of neonatal alcohol-induced oxidative stress. Seventy ten-day-old Sprague-Dawley rat pups (35 male, 35 female) were randomly assigned and administered the following treatment regimens daily from postnatal day (PND) 12-21: group 1 - nutritive milk (NM), group 2 - NM +1 g/kg ethanol (Eth), group 3 - NM + 40 mg/kg ZO, group 4 - NM + Eth + ZO. Growth performance, blood glucose and plasma triglycerides (TGs), total cholesterol, HDL-cholesterol, leptin and insulin concentration were determined. Cytochrome p450E21(CYP2E1) and thiobarbituric acid (TBARS); markers of hepatic oxidative stress and catalase, superoxide dismutase (SOD) and total glutathione (GSH), anti-oxidant markers of the pups were determined. Oral administration of ethanol (NM + Eth), zingerone (NM + ZO) and combined ethanol and zingerone (NM + Eth + ZO) did not affect the growth performance and insulin and leptin concentration of the rats (p > 0.05). Ethanol significantly reduced plasma TGs concentration of female rats (p = 0.04 vs control). However, ethanol and/or its combination with zingerone decreased hepatic GSH (p = 0.02 vs control) and increased CYP2E1 (p = 0.0002 vs control) activity in male rat pups. Zingerone had no effect (p > 0.05 vs control) on the rats' CYP2E1, GSH, SOD and catalase activities. Neonatal alcohol administration elicited hepatic oxidative stress in male rat pups only, showing sexual dimorphism. Zingerone (NM + ZO) prevented an increase in CYP2E1 activity and a decrease in GSH concentration but did not prevent the alcohol-induced hepatic oxidative stress in the male rat pups.


Assuntos
Antioxidantes , Insulinas , Ratos , Masculino , Feminino , Animais , Ratos Sprague-Dawley , Antioxidantes/farmacologia , Catalase/metabolismo , Leptina/farmacologia , Citocromo P-450 CYP2E1 , Estresse Oxidativo , Etanol/toxicidade , Glutationa/metabolismo , Superóxido Dismutase/metabolismo , Insulinas/farmacologia
6.
Cell Biochem Funct ; 40(6): 608-622, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35789495

RESUMO

Cancer is the second leading cause of mortality worldwide. Skin cancer is the most common cancer in South Africa with nearly 20,000 reported cases every year and 700 deaths. If diagnosed early, the 5-year survival rate is about 90%, however, when diagnosed late, the 5-year survival rate decreases to about 20%. Melanoma is a type of skin cancer with an estimated 5-year survival rate of approximately 90%. Neuroblastoma is a paediatric cancer with a low survival rate. Sixty percent of patients with metastatic disease do not survive 5 years after diagnosis. Despite recent advances in targeted therapies, there is a crucial need to identify reliable prognostic biomarkers which will be able to contribute to the development of more precision-based chemotherapeutic strategies to prevent tumour migration and metastasis. The compound, CTCE-9908 inhibits the binding of CXC chemokine ligand 12 (CXCL12) to the CXC chemokine receptor 4 (CXCR4) receptor leading to reduced metastasis. Kynurenine metabolites are derived tryptophan, which is an essential amino acid. Kynurenine metabolites inhibit T-cell proliferation resulting in cell growth arrest. For this reason, chemokines receptors represent potential targets for the treatment of cancer growth and metastasis. In this review paper, the role of the CXCL12/CXCR4 signalling pathway in the development of cancer is highlighted together with the current available treatments involving the CTCE-9908 compound in combination with microtubule inhibitors like paclitaxel and docetaxel.


Assuntos
Melanoma , Neoplasias Cutâneas , Quimiocina CXCL12 , Quimiocinas CXC , Criança , Humanos , Cinurenina , Melanoma/tratamento farmacológico , Peptídeos/farmacologia , Receptores CXCR4
7.
Life (Basel) ; 12(6)2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35743821

RESUMO

High-fructose diets are linked with the development of non-alcoholic fatty liver disease (NAFLD), the management of which is a burden to society. Interventions with phytochemicals in the early postnatal period may prevent fructose-induced NAFLD later in adulthood. We investigated the protective potential of chrysin against fructose-induced NAFLD. Four-day-old male and female suckling Sprague Dawley rats (N = 112) were randomly grouped and orally gavaged daily with distilled water (negative Control-Cn + W), chrysin(Chr-100 mg/kg), fructose-solution (Fr-20% w/v), and Chr + Fr between postnatal day (PND) 4 and 21 and then weaned onto normal rat chow and plain drinking water to PND 55. From PND 56 to 130, half of the rats continued on plain water, and the rest had Fr as drinking fluid. Terminally, the liver tissue was collected, and the lipid content was determined and histologically assessed for NAFLD. Dietary Fr induced an increased hepatic lipid content (p = 0.0001 vs. Cn + W) both sexes, and it was only attenuated by neonatal Chr in female rats (p < 0.05). Histologically, there was increased microvesicular steatosis (p = 0.0001 vs. Cn + W) in both sexes, and it was prevented by neonatal Chr (p > 0.05). Fr caused macrovesicular steatosis (p = 0.01 vs. Cn + W) in females only, and chrysin did not prevent it (p > 0.05). Fr induced hepatocellular hypertrophy, and inflammation was observed in females only (p = 0.01 vs. Cn + W), and this was prevented by Chr (p > 0.05). The collagen area fraction was increased by Fr (p = 0.02 (males) and p = 0.04 (females) vs. Cn + W, respectively; however, chrysin did not prevent this (p > 0.05). Neonatal chrysin prevented some of the deleterious effects of the high-fructose diet on the liver, suggesting that chrysin should be further explored as a strategic prophylactic neonatal intervention against high-fructose-diet-induced NAFLD.

8.
Birth Defects Res ; 113(6): 451-468, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33577143

RESUMO

Alcohol consumption remains prevalent among pregnant and nursing mothers despite the well-documented adverse effects this may have on the offspring. Moderate-to-high levels of alcohol consumption in pregnancy result in fetal alcohol syndrome (FAS) disorders, with brain defects being chief among the abnormalities. Recent findings indicate that while light-to-moderate levels may not cause FAS, it may contribute to epigenetic changes that make the offspring prone to adverse health outcomes including metabolic disorders and an increased propensity in the adolescent-onset of drinking alcohol. On the one hand, prenatal alcohol exposure (PAE) causes epigenetic changes that affect lipid and glucose transcript regulating genes resulting in metabolic abnormalities. On the other hand, it can program offspring for increased alcohol intake, enhance its palatability, and increase acceptance of alcohol's flavor through associative learning, making alcohol a plausible second hit for the development of alcohol-induced liver disease. Adolescent drinking results in alcohol dependence and abuse in adulthood. Adolescent drinking results in alcohol dependence and abuse in adulthood. Alterations on the opioid system, particularly, the mu-opioid system, has been implicated in the mechanism that induces increased alcohol consumption and acceptance. This review proposes a mechanism that links PAE to the development of alcoholism and eventually to alcoholic liver disease (ALD), which results from prolonged alcohol consumption. While PAE may not lead to ALD development in childhood, there are chances that it may lead to ALD in adulthood.


Assuntos
Transtornos do Espectro Alcoólico Fetal , Hepatopatias Alcoólicas , Efeitos Tardios da Exposição Pré-Natal , Consumo de Bebidas Alcoólicas/efeitos adversos , Etanol/efeitos adversos , Feminino , Transtornos do Espectro Alcoólico Fetal/etiologia , Humanos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente
9.
Molecules ; 25(11)2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-32526850

RESUMO

Metabolic syndrome (MetS) is a prevalent, multifactorial and complex disease that is associated with an increased risk of developing diabetes and other major cardiovascular complications. The rise in the global prevalence of MetS has been attributed to genetic, epigenetic, and environmental factors. The adoption of sedentary lifestyles that are characterized by low physical activity and the consumption of high-energy diets contributes to MetS development. Current management criteria for MetS risk factors involve changes in lifestyle and the use of pharmacological agents that target specific biochemical pathways involved in the metabolism of nutrients. Pharmaceutical drugs are usually expensive and are associated with several undesirable side effects. Alternative management strategies of MetS risk factors involve the use of medicinal plants that are considered to have multiple therapeutic targets and are easily accessible. Medicinal plants contain several different biologically active compounds that provide health benefits. The impact of phytochemicals present in local medicinal plants on sustainable health and well-being of individuals has been studied for many years and found to involve a plethora of complex biochemical, metabolic, and physiological mechanisms. While some of these phytochemicals are the basis of mainstream prescribed drugs (e.g., metformin, reserpine, quinine, and salicin), there is a need to identify more medicinal plants that can be used for the management of components of MetS and to describe their possible mechanisms of action. In this review, we assess the potential health benefits of South African ethnomedicinal plants in protecting against the development of health outcomes associated with MetS. We aim to provide the state of the current knowledge on the use of medicinal plants and their therapeutically important phytochemicals by discussing the current trends, with critical examples from recent primary references of how medicinal plants are being used in South African rural and urban communities.


Assuntos
Doenças Metabólicas/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Fitoterapia , Plantas Medicinais/química , Animais , Humanos
10.
Molecules ; 25(9)2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32366012

RESUMO

The development of risk factors associated with cardiovascular disorders present a major public health challenge in both developed countries and countries with emerging economies. Hypertension and associated complications including stroke and myocardial infarction have reached pandemic levels. Current management strategies of hypertension predominantly include the utilization of pharmaceutical drugs which are often associated with undesirable side effects. Moreover, the drugs are often too expensive for populations from resource-limited Southern African rural, and some urban, communities. As a result, most patients rely on ethno-medicinal plants for the treatment of a variety of diseases including cardiovascular and metabolic disorders. The effectiveness of these plants in managing several cardiovascular diseases has been attributed to the presence of bioactive phytochemical constituents. In this review, the treatment options that target the renin-angiotensin system (RAS) in the management of hypertension were summarized, with special emphasis on ethno-medicinal plants and their influence on the ACE1 RAS pathway. The dearth of knowledge regarding the effect of ethno-medicinal plants on the ACE2 pathway was also highlighted.


Assuntos
Anti-Hipertensivos/química , Anti-Hipertensivos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Sistema Renina-Angiotensina/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Desenvolvimento de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Humanos , Hipertensão/tratamento farmacológico , Medicina Tradicional , Terapia de Alvo Molecular , Peptidil Dipeptidase A/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas ras/metabolismo
11.
Plants (Basel) ; 8(11)2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31731759

RESUMO

This paper reviews the properties of the most cultivated species of the Moringaceae family, Moringa oleifera Lam. The paper takes a critical look at the positive and the associated negative properties of the plant, with particular emphasis on its chemistry, selected medicinal and nutritional properties, as well as some ecological implications of the plant. The review highlights the importance of glucosinolates (GS) compounds which are relatively unique to the Moringa species family, with glucomoriginin and its acylated derivative being the most abundant. We highlight some new research findings revealing that not all M. oleifera cultivars contain an important flavonoid, rutin. The review also focuses on phenolic acids, tannin, minerals and vitamins, which are in high amounts when compared to most vegetables and fruits. Although there are numerous benefits of using M. oleifera for medicinal purposes, there are reports of contraindications. Nonetheless, we note that there are no major harmful effects of M. oleifera that have been reported by the scientific community. M. oleifera is suspected to be potentially invasive and moderately invasive in some regions of the world because of its ability to grow in a wide range of environmental conditions. However, the plant is currently classified as a low potential invasive species and thus there is a need to constantly monitor the species. Despite the numerous benefits associated with the plant, there is still a paucity of data on clinical trials proving both the positive and negative effects of the plant. We recommend further clinical trials to ascertain the properties associated with the plant, especially regarding long term use.

12.
Molecules ; 24(4)2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30781794

RESUMO

Nutritional manipulations in the neonatal period are associated with the development of negative or positive health outcomes later in life. Excessive fructose consumption has been attributed to the increase in the global prevalence of metabolic syndrome (MetS) and the development of oxidative stress. Oleanolic acid (OA) has anti-diabetic and anti-obesity effects. We investigated the protective potential of orally administering OA in the neonatal period, to prevent fructose-induced oxidative stress, adverse health outcomes and maturation of the gastrointestinal tract (GIT) in suckling rats. Seven-day old Sprague-Dawley rats (N = 30) were gavaged daily with 10 mL/kg of: distilled water (DW), oleanolic acid (OA; 60 mg/kg), high fructose solution (HF; 20% w/v), or OAHF for 7 days. On day 14, tissue samples were collected to determine clinical health profiles, hepatic lipid content, and activity of anti-oxidant enzymes. Furthermore, biomarkers of oxidative stress and anti-oxidant capacity in the skeletal muscles were assessed. The gastrointestinal tract (GIT) morphometry was measured. Rats in all groups grew over the 7-day treatment period. There were no significant differences in the terminal body masses, GIT morphometry, surrogate markers of general health, liver lipid content across all treatment groups (p < 0.05). Neonatal fructose administration decreased the activity of catalase, depleted GSH and increased lipid peroxidation. However, the level of GSH and catalase activity were improved by neonatal OA treatment. Short-term oral OA administration during the critical developmental period protects against fructose-induced oxidative stress without adverse effects on health outcomes associated with MetS or precocious development of the GIT in suckling male and female rats.


Assuntos
Músculo Esquelético/efeitos dos fármacos , Obesidade/dietoterapia , Ácido Oleanólico/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Administração Oral , Animais , Animais Recém-Nascidos , Animais Lactentes , Frutose/efeitos adversos , Frutose/toxicidade , Humanos , Músculo Esquelético/patologia , Obesidade/patologia , Ratos
13.
Nutrients ; 11(2)2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30678182

RESUMO

AMP-activated protein kinase (AMPK) is known to regulate both glucose and lipid metabolism, which play vital roles in the development of metabolic syndrome. One way of regulating AMPK is through hormonal activation using adiponectin. Patients diagnosed with type-2 diabetes (T2D) and obesity exhibit low adiponectin concentration levels in their blood. Moreover, studies have also shown that inflammatory processes play a significant role in the etiology of these metabolic diseases. In this study, the long-term effects of neonatal intake of oleanolic acid (OA) on the AMPK gene, genes associated with glucose transport and lipid metabolism, adiponectin levels, and inflammatory biomarkers in rats fed with a high fructose diet were investigated. Seven day old pups were randomly divided into five groups and treated as follows; 0.5% dimethylsulphoxide v/v in distilled water vehicle control (CON), oleanolic acid (OA, 60 mg/kg), high fructose diet (HF, 20% w/v), high fructose diet combined with oleanolic acid (HF+OA), and high fructose diet combined with metformin (HF+MET, 500 mg/kg). The treatments were administered once daily until day 14. The rats were then weaned at day 21 and fed standard rat chow and had ad libitum access to plain drinking water until day 112. The quantitative polymerase chain reaction (qPCR) was used to analyze the gene expressions of AMPK, Glut-4, Cpt-1, AdipoR1, AdipoR2, TNF-α, and IL-6 in the skeletal muscles. Bio-Plex Pro magnetic bead-based assay was used to measure plasma levels of inflammatory markers (TNF-α, IL-6, VEGF, and MCP-1) while ELISA kits were used to measure adiponectin concentration in blood plasma. The results obtained in this study showed that neonatal supplementation with OA significantly increased AMPK gene expression approximately ~4-fold in OA fed rats compared to those that were fed with HF alone. In addition, glut-4 gene expression was also significantly higher in the OA treatment group compared to all the other experimental groups except the CON group whereas Cpt-1 gene was more expressed when OA was administered alone. Together, these results indicated that OA can play a role in glucose and lipid metabolism gene regulation. Furthermore, the results showed that the OA group had ~1.5-fold increase in adiponectin concentration when comparedto the HF group. Moreover, HF increased levels of inflammatory cytokines, which was attenuated by neonatal administration of OA. Plasma concentration and gene expression in the skeletal muscle for TNF-α and IL-6 were significantly increased in rats that were treated with HF alone when compared to all the other groups. On the contrary, the high levels of TNF-α and IL-6 were reduced when OA was administered. These findings suggest that intake of oleanolic acid during the neonatal stage of development could be a potential strategic intervention for the long-term prevention of metabolic diseases such as T2D and obesity.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adiponectina/metabolismo , Citocinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Ácido Oleanólico/farmacologia , Proteínas Quinases Ativadas por AMP/genética , Adiponectina/genética , Animais , Animais Recém-Nascidos , Citocinas/genética , Carboidratos da Dieta/administração & dosagem , Carboidratos da Dieta/efeitos adversos , Frutose/administração & dosagem , Frutose/efeitos adversos , Inflamação/metabolismo , Masculino , Ácido Oleanólico/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
14.
Nutr Metab (Lond) ; 15: 82, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30479649

RESUMO

BACKGROUND: Consumption of fructose-rich diets has been implicated in the increasing global prevalence of metabolic syndrome (MetS). Interventions during periods of early ontogenic developmental plasticity can cause epigenetic changes which program metabolism for positive or negative health benefits later in life. The phytochemical oleanolic acid (OA) possesses anti-diabetic and anti-obesity effects. We investigated the potential protective effects of neonatal administration of OA on the subsequent development of high fructose diet-induced metabolic dysfunction in rats. METHOD: Male and female (N = 112) suckling rats were randomly assigned to four groups and administered orally: distilled water (DW), oleanolic acid (OA; 60 mg/kg), high-fructose solution (HF; 20% w/v) or OA + HF for 7 days. The rats were weaned onto normal commercial rat chow up to day 55. From day 56, half of the rats in each treatment group were continued on plain water and the rest on a high fructose solution as drinking fluid for 8 weeks. On day 110, the rats were subjected to an oral glucose tolerance test and then euthanased on day 112. Tissue and blood samples were collected to determine the effects of the treatments on visceral fat pad mass, fasting plasma levels of cholesterol, insulin, glucose, triglycerides, insulin resistance (HOMA-IR) and glucose tolerance. RESULTS: Rats which consumed fructose as neonates and then later as adults (HF + F) and those which consumed fructose only in adulthood (DW + F) had significant increases in terminal body mass (females only), visceral fat mass (males and females), serum triglycerides (females only), epididymal fat (males only), fasting plasma glucose (males and females), impaired glucose metabolism (females only), ß-cell dysfunction and insulin resistance (males and females) compared to the other treatment groups (P < 0.05). There were no differences in fasting serum cholesterol levels across all treatment groups in both male and female rats (P > 0.05). CONCLUSION: We conclude that neonatal oral administration of OA during the critical window of developmental plasticity protected against the development of health outcomes associated with fructose-induced metabolic disorders in the rats.

15.
Molecules ; 23(10)2018 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-30282899

RESUMO

Metabolic syndrome, a cluster of different disorders which include diabetes, obesity and cardiovascular diseases, is a global epidemic that is growing at an alarming rate. The origins of disease can be traced back to early developmental stages of life. This has increased mortalities and continues to reduce life expectancies of individuals across the globe. The aim of this study was to investigate the sub-acute and long term effects of neonatal oral administration of oleanolic acid and metformin on lipids (free fatty acids, FFAs) and genes associated with lipid metabolism and glucose transport using a neonatal rat experimental model. In the first study, seven days old pups were randomly grouped into control-distilled water (DW); oleanolic acid (60 mg/kg), metformin (500 mg/kg), high fructose diet (20% w/v, HF), oleanolic acid (OA) + high fructose diet (OA + HF), and Metformin + high fructose diet (MET + HF) groups. The pups were treated for 7 days, and then terminated on postnatal day (PD) 14. In the second study, rat pups were initially treated similarly to study 1 and weaned onto normal rat chow and plain drinking water on PD 21 till they reached adulthood (PD112). Tissue and blood samples were collected for further analyses. Measurement of the levels of free fatty acids (FFAs) was done using gas chromatography-mass spectrometry. Quantitative polymerase chain reaction (qPCR) was used to analyze the gene expression of glut-4, glut-5, fas, acc-1, nrf-1 and cpt-1 in the skeletal muscle. The results showed that HF accelerated accumulation of saturated FFAs within skeletal muscles. The HF fed neonatal rats had increased stearic acid, which was associated with decreased glucose, suppressed expression of glut-4, glut-5, nrf-1 and cpt-1 genes, and increased expression of acc-1 (p < 0.01) and fas. OA + HF and MET + HF treated groups had increased mono- and polyunsaturated FFAs; oleic, and octadecadienoic acids than the HF group. These unsaturated FFAs were associated with increased glut-4, glut-5 and nrf-1 (p < 0.01) and decreased acc-1 and fas (p < 0.05) in both OA + HF and MET + HF treated groups. CONCLUSIONS: The present study shows that neonatal oral administration of oleanolic acid and metformin potentially protects against the development of fructose-induced metabolic dysfunction in the rats in both short and long time periods.


Assuntos
Metabolismo dos Lipídeos/efeitos dos fármacos , Síndrome Metabólica/tratamento farmacológico , Metformina/administração & dosagem , Ácido Oleanólico/administração & dosagem , Animais , Animais Recém-Nascidos , Transporte Biológico/efeitos dos fármacos , Glicemia/metabolismo , Gorduras na Dieta/administração & dosagem , Proteínas Facilitadoras de Transporte de Glucose/efeitos dos fármacos , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Humanos , Masculino , Síndrome Metabólica/metabolismo , Ratos , Ratos Sprague-Dawley
16.
Am J Primatol ; 74(12): 1143-53, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22930453

RESUMO

We investigated the temporal relationship between abdominal temperature, physical activity, perineal swelling, and urinary progesterone and estradiol concentrations over the menstrual cycle in unrestrained captive baboons. Using a miniature temperature-sensitive data logger surgically implanted in the abdominal cavity and an activity data logger implanted subcutaneously on the trunk, we measured, continuously over 6 months at 10-min intervals, abdominal temperature and physical activity patterns in four female adult baboons Papio hamadryas ursinus (12.9-19.9 kg), in cages in an indoor animal facility (22-25°C). We monitored menstrual bleeding and perineal swelling changes, and measured urinary progesterone and estradiol concentrations, daily for up to 6 months, to ascertain the stage and length of the menstrual cycle. The menstrual cycle was 36 ± 2 days (mean ± SD) long and the baboons exhibited cyclic changes in perineal swellings, abdominal temperature, physical activity, urinary progesterone, and estradiol concentrations over the cycle. Mean 24-hr abdominal temperature during the luteal phase was significantly higher than during the periovulatory phase (ANOVA, F((2, 9)) = 4.7; P = 0.04), but not different to that during the proliferative phase. Physical activity followed a similar pattern, with mean 24-hr physical activity almost twice as high in the luteal than in the periovulatory phase (ANOVA, P = 0.58; F((2, 12)) = 5.8). We have characterized correlates of the menstrual cycle in baboons and shown, for the first time, a rhythm of physical activity and abdominal temperature over the menstrual cycle, with a nadir of temperature and activity at ovulation.


Assuntos
Temperatura Corporal , Ciclo Menstrual , Atividade Motora , Ovulação , Papio ursinus/fisiologia , Animais , Estradiol/urina , Feminino , Períneo/fisiologia , Progesterona/urina
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA