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1.
Einstein (Sao Paulo) ; 18: eAO4876, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31576909

RESUMO

OBJECTIVE: To investigate the effects of sericin extracted from silkworm Bombyx mori cocoon on morphophysiological parameters in mice with obesity induced by high-fat diet. METHODS: Male C57Bl6 mice aged 9 weeks were allocated to one of two groups - Control and Obese, and fed a standard or high-fat diet for 10 weeks, respectively. Mice were then further subdivided into four groups with seven mice each, as follows: Control, Control-Sericin, Obese, and Obese-Sericin. The standard or high fat diet was given for 4 more weeks; sericin (1,000mg/kg body weight) was given orally to mice in the Control-Sericin and Obese-Sericin Groups during this period. Weight gain, food intake, fecal weight, fecal lipid content, gut motility and glucose tolerance were monitored. At the end of experimental period, plasma was collected for biochemical analysis. Samples of white adipose tissue, liver and jejunum were collected and processed for light microscopy analysis; liver fragments were used for lipid content determination. RESULTS: Obese mice experienced significantly greater weight gain and fat accumulation and had higher total cholesterol and glucose levels compared to controls. Retroperitoneal and periepididymal adipocyte hypertrophy, development of hepatic steatosis, increased cholesterol and triglyceride levels and morphometric changes in the jejunal wall were observed. CONCLUSION: Physiological changes induced by obesity were not fully reverted by sericin; however, sericin treatment restored jejunal morphometry and increased lipid excretion in feces in obese mice, suggesting potential anti-obesity effects.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Dieta Hiperlipídica , Obesidade/tratamento farmacológico , Sericinas/uso terapêutico , Tecido Adiposo/patologia , Animais , Fármacos Antiobesidade/farmacologia , Peso Corporal/efeitos dos fármacos , Colesterol/análise , Dieta Hiperlipídica/efeitos adversos , Ingestão de Alimentos/efeitos dos fármacos , Fígado Gorduroso/patologia , Trânsito Gastrointestinal/efeitos dos fármacos , Teste de Tolerância a Glucose , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/etiologia , Obesidade/fisiopatologia , Reprodutibilidade dos Testes , Sericinas/farmacologia , Fatores de Tempo , Resultado do Tratamento , Triglicerídeos/análise , Ganho de Peso/efeitos dos fármacos
2.
Int J Clin Pract ; 73(11): e13399, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31397946

RESUMO

AIMS: To evaluate in a real-world setting the effectiveness of two drugs, orlistat and liraglutide, in patients with overweight or obesity and insufficient weight loss (WL) after a lifestyle modification programme. METHODS: Retrospective, observational cohort study comparing clinical outcomes of orlistat 120 mg three times a day and liraglutide (up to 3 mg daily) in adult patients with BMI ≥30 kg/m2 or ≥27 kg/m2 with at least a weight-related comorbidity who had failed to lose at least 5% of their weight after 6 months of lifestyle modification. The co-primary end-points, assessed at 3-6 months and at the end of the follow-up, were weight change from baseline, proportion of patients who lost at least 5% of their baseline weight and adjusted differences in WL between both drugs. RESULTS: Five hundred patients, 400 in the group of orlistat (age 47.0, weight 107.8 kg) and 100 in the group of liraglutide (age 51.9 years, weight 105.1 kg), were included. Treatment with both drugs significantly reduced weight, fasting plasma glucose, systolic BP, low-density lipoprotein-cholesterol and alanine transaminase over a median follow-up period of 7 months. WL with liraglutide (-7.7 kg) was significantly greater than that observed with orlistat (-3.3 kg), and more individuals lost at least 5% of their baseline weight with liraglutide (64.7%) than with orlistat (27.4%). Rates of prediabetes significantly decreased with liraglutide in comparison to orlistat. CONCLUSIONS: In this real-world study, liraglutide showed a greater effectiveness in WL compared with orlistat and improved several obesity-associated metabolic and cardiovascular risk factors.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Liraglutida/uso terapêutico , Obesidade/tratamento farmacológico , Orlistate/uso terapêutico , Adulto , Estudos de Coortes , Feminino , Humanos , Lactonas/uso terapêutico , Estilo de Vida , Liraglutida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Orlistate/efeitos adversos , Sobrepeso/tratamento farmacológico , Estudos Retrospectivos , Perda de Peso/efeitos dos fármacos
3.
Nutrients ; 11(7)2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31277301

RESUMO

The edible seaweed Gelidium elegans (GEE) is known to inhibit adipocyte differentiation. However, there has been no report on its effects in humans. In this study, we investigated whether GEE reduces body weight or fat mass in obese or overweight individuals. A total of 78 participants were randomly assigned to the test (GEE extract 1000 mg/day) and placebo groups at a 1:1 ratio, and treated for 12 weeks. At six or 12 weeks after randomization, they were evaluated for anthropometric parameters, biomarkers, and body composition. Changes in body weight and fat mass between the two groups was significantly different, as determined using ANCOVA adjusted for baseline, calorie intake, and physical activity. Body weight and fat mass were significantly decreased by GEE after 12 weeks but increased in the placebo group. Moreover, although not significant, triglyceride levels tended to decrease after GEE intake. There was no significant difference in other laboratory biomarkers between the two groups. Taken together, these results suggested that GEE significantly reduced body weight, especially fat mass, in overweight or obese individuals.


Assuntos
Adiposidade/efeitos dos fármacos , Fármacos Antiobesidade/uso terapêutico , Suplementos Nutricionais , Obesidade/tratamento farmacológico , Alga Marinha/química , Perda de Peso/efeitos dos fármacos , Adulto , Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/isolamento & purificação , Biomarcadores/sangue , Suplementos Nutricionais/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
4.
Acta Histochem ; 121(5): 646-656, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31153588

RESUMO

Obesity, type two diabetes mellitus and insulin resistance are associated with increased oxidative stress and inflammation. Unfermented green rooibos is an aspalathin rich variant of traditional fermented rooibos (Aspalathus linearis) and has a high polyphenol content. The present study aimed to determine the histologically observable effects of a commercially produced, aspalathin-rich green rooibos extract, Afriplex GRT™ (GRE) in a diet-induced obese rat model. Male Wistar rats (N = 28) were randomly assigned to four study groups (n = 7): control (C), green rooibos (GRT), high-fat diet (HFD) and experimental (HFD-GRT) group. Body mass was determined prior to euthanasia and liver mass was determined after death. The left lateral lobe of the liver was processed to wax and stained using haematoxylin and eosin (H & E), Masson's trichrome stain, Gordons and Sweet's reticulin impregnation and periodic acid-Schiff stain. Frozen liver tissue sections were used for Oil red O staining. Morphometric quantification of steatosis, semiquantitative pathology grading and scoring were performed and verified by a veterinary histopathologist. A significant increase in body and liver mass was observed in the HFD groups while co-treatment with green rooibos significantly reduced both. The volume and area of steatosis were significantly increased in the HFD groups while the area of steatosis significantly reduced with green rooibos co-treatment. The percentage, location and type of steatosis as well as presence of inflammation and hepatocellular injury were reduced in the HFD group co-treated with GRE. These findings suggest that a GRE has potential as an anti-steatotic, anti-inflammatory and weight reducing agent in vivo.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Aspalathus , Fígado/citologia , Fígado/patologia , Obesidade/tratamento farmacológico , Fitoterapia , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Fígado Gorduroso/patologia , Histocitoquímica , Masculino , Obesidade/etiologia , Obesidade/patologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar
5.
Carbohydr Polym ; 220: 60-70, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31196551

RESUMO

Chitosan oligosaccharides (COS) are the degraded products of chitin or chitosan prepared by chemical or enzymatic hydrolysis. As compared to chitosan, COS not only exhibit some specific physicochemical properties such as excellent water solubility, biodegradability and biocompatibility, but also have a variety of functionally biological activities including anti-inflammation, anti-bacteria, immunomodulation, neuroprotection and so on. This review aims to summarize the preparation and structural characterization methods of COS, and will discuss the application of COS or their derivatives to human health, animal husbandry and agricultural production. COS have been demonstrated to prevent the occurrence of human health-related diseases, enhance the resistance to diseases of livestock and poultry, and improve the growth and quality of crops in plant cultivation. Overall, COS have presented a broad developmental potential and application prospect in the healthy field that deserves further exploration.


Assuntos
Quitosana , Criação de Animais Domésticos , Animais , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Fármacos Antiobesidade/uso terapêutico , Antineoplásicos/uso terapêutico , Antioxidantes/uso terapêutico , Quitosana/química , Quitosana/isolamento & purificação , Quitosana/farmacologia , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/metabolismo , Humanos , Gado/crescimento & desenvolvimento , Gado/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Doenças das Plantas/prevenção & controle
6.
Biomed Pharmacother ; 117: 109042, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31228804

RESUMO

AIMS: Scutellarein (Sc), a natural compound and an active ingredient of Erigeron breviscapus (vant.), shows anti-inflammatory and antioxidant properties and has the potential for obesity treatment. However, no previous in vivo study has been conducted to assess the role of Sc in obesity. This study investigated the effects of Sc on obesity and associated hyperlipidemia and fatty liver and explores the underlying mechanisms of action in a mouse model. METHODS: The study was conducted using a well-established mouse model of obesity induced by high-fat diet (HFD) feeding. Anti-obesity effects were assessed using body weight, abdominal circumference, white adipose tissue, adiposity index, and fatty liver index. Lipid lowering and liver protective effects were examined by blood sample analysis. Lipid dystopia deposition was confirmed by liver pathological sections. The signaling pathways of lipid metabolism and cytokine/inflammatory mediator were evaluated using Real-Time PCR and Western blot. RESULTS: Central obesity, dyslipidemia, inflammation, and hepatic steatosis were developed in mice fed with HFD. Administration of Sc at a dose of 50 mg/kg for 16 weeks effectively attenuated all obesity indicators tested. Further studies revealed the antagonistic effect of Sc on hyperlipidemia was a result of the repression of the lipid synthesis pathway, de novo pathway, HMGCR, promoting fatty acid oxidation (PPARα, CPT-1a) and increased cholesterol output (PPARγ-LXRα-ABCA1). The anti-inflammatory effect was attributed to blocking the expression of inflammatory genes, including TNF-α, IL-6, NF-κB. CONCLUSIONS: These results suggest that Sc possesses important novel anti-obesity effects accompanying lipid lowering and anti-inflammation-based liver protective effects. These favorable effects are causally associated with the suppression of gene expression of inflammatory cytokines and fine regulation of genes responsible for energy metabolism. Our results advance the understanding of the pharmacological actions of Sc, and provides a role for Sc in effective management of obesity.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Apigenina/uso terapêutico , Obesidade/tratamento farmacológico , Animais , Fármacos Antiobesidade/química , Fármacos Antiobesidade/farmacologia , Apigenina/química , Apigenina/farmacologia , Peso Corporal/efeitos dos fármacos , Citocinas/metabolismo , Dieta Hiperlipídica , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperlipidemias/complicações , Hiperlipidemias/fisiopatologia , Inflamação/patologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Lipídeos/sangue , Fígado/metabolismo , Fígado/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Obesidade/complicações , Obesidade/genética , Obesidade/fisiopatologia , Tamanho do Órgão/efeitos dos fármacos
7.
Endocr Pract ; 25(10): 1022-1028, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31241358

RESUMO

Objective: The effectiveness of anti-obesity medications (AOMs) outside of clinical trials is unclear. The objective of this study was to compare the short-term effectiveness of AOMs in real-world practice. Methods: This retrospective study included adults aged ≥18 years, with body mass index ≥30 kg/m2 or ≥27 kg/m2 with at least one obesity-related comorbidity who were prescribed phentermine hydrochloride, phenterminetopiramate, bupropion-naltrexone, or lorcaserin for 12 consecutive weeks between 2006 and 2016 at a large tertiary healthcare system. Propensity score-matched cohorts were created for each pair of AOMs. The primary outcomes were percent and absolute weight loss from baseline after 12 weeks. A prediction model was constructed to estimate weight loss with different AOMs based on demographic and clinical data. Results: Of the 3,411 patients included in this study, patients lost an average of 3.45% of body weight from baseline. All AOMs were associated with a significant weight loss from baseline (P<.0001). Patients lost the highest percentage of body weight on phentermine hydrochloride (3.75 ± 5.66%), followed by phentermine-topiramate (3.63 ± 5.7%), bupropion-naltrexone (2.66 ± 5.03%), and lorcaserin (1.84 ± 6.69%). In propensity-matched cohorts, patients taking phentermine hydrochloride lost more weight than those taking lorcaserin or bupropion-naltrexone, and patients taking phentermine topiramate lost more weight than patients taking lorcaserin. Conclusion: In real-world practice, AOMs are associated with clinically meaningful weight loss of 2 to 4% after 12 weeks. In this study, phentermine hydrochloride and phentermine topiramate produced the most weight loss. AOMs should be seriously considered as part of the armamentarium to treat patients with obesity. Abbreviations: AOM = anti-obesity medication; BMI = body mass index; EMR = electronic medical record; FDA = Food and Drug Administration; T2D = type 2 diabetes.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Diabetes Mellitus Tipo 2 , Perda de Peso , Adulto , Frutose , Humanos , Obesidade/tratamento farmacológico , Estudos Retrospectivos , Topiramato
8.
J Ethnopharmacol ; 241: 112032, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31220598

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional herbal medicine has been taken as a new and effective approach to treat many chronic diseases. Xiexin Tang (XXT), a compound recipe composed of Dahuang (Rheum palmatum L.), Huangqin (Scutellaria baicalensis Georgi) and Huanglian (Coptis chinensis Franch.), has been reported to have hypoglycemic and hypolipidemic effects, but its mechanism remains unclear. Our previous study found that Xiexin Tang markedly ameliorated the composition of the gut microbiota, especially for some short chain fatty acids (SCFAs) producing bacteria, and then notably increased SCFAs production. However, the mechanism of XXT on the fermentation of gut bacteria and further improvement of obesity is not yet clear. AIM OF THE STUDY: This study aimed to unravel the molecular mechanism of XXT on the amelioration of obesity. MATERIALS AND METHODS: Here, high-fat diet-induced obese rat model was established to investigate the intervention efficacy following oral administration of XXT. Additionally, the expressions of key enzymes of gut microbe-derived SCFAs biosynthesis and key targets in the signaling pathway of energy metabolism were investigated by ELISA and qPCR analysis. RESULTS: Results showed that XXT could notably correct lipid metabolism disorders, alleviate systematic inflammation, improve insulin sensitivity and reduce fat accumulation. Additionally, XXT could increase gut microbiota-derived SCFAs-producing capacity by enhancing mRNA levels and activities of SCFA-synthetic key enzymes such as acetate kinase (ACK), methylmalonyl-CoA decarboxylase (MMD), butyryl-CoA: acetate CoA transferase (BUT) and butyrate kinase (BUK), which markedly decreased the adenosine triphosphate (ATP) contents, elevated adenosine diphosphate (ADP) and adenosine monophosphate (AMP) levels and further lowered the energy charge (EC) in obese rats via activating peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)/uncoupling protein-2 (UCP-2) signaling pathway. What's more, XXT could notably ameliorate dyslipidemia via increasing the gene expression of 5'-AMP-activated protein kinase (AMPK) and blocking mammalian target of rapamycin (mTOR) signaling pathway. CONCLUSIONS: Taken together, our data provided a novel insight into the role of XXT in losing weight from energy metabolism regulation, which unraveled the molecular mechanism of XXT on the alleviation of dyslipidemia and fat heterotopic accumulation. The study provided useful information for XXT in clinical application to treat obesity.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Dislipidemias/tratamento farmacológico , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal , Hipolipemiantes/uso terapêutico , Obesidade/tratamento farmacológico , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/patologia , Animais , Fármacos Antiobesidade/farmacologia , Dieta Hiperlipídica , Medicamentos de Ervas Chinesas/farmacologia , Dislipidemias/metabolismo , Dislipidemias/microbiologia , Dislipidemias/patologia , Metabolismo Energético/efeitos dos fármacos , Hipolipemiantes/farmacologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Obesidade/metabolismo , Obesidade/microbiologia , Obesidade/patologia , Ratos Sprague-Dawley
9.
Curr Med Sci ; 39(3): 349-355, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31209802

RESUMO

Peptides play crucial roles in various physiological and pathological processes. Consequently, the investigation of peptide-based drugs is a highlight in the research and development of new drugs. However, natural peptides are not always ideal choices for clinical application due to their limited number and sometimes cytotoxicity to normal cells. Aiming to gain stronger or specific or novel biological effects and overcome the disadvantages of natural peptides, artificial hybrid peptides have been designed by combining the sequence of two or more different peptides with varied biological functions. Compared to natural peptides, hybrid peptides have shown better therapeutic potentials against bacteria, tumors, and metabolic diseases. In this review, design strategies, structure features and recent development of hybrid peptides are summarized; future directions for the research and development of hybrid peptide drugs are also discussed.


Assuntos
Peptídeos Catiônicos Antimicrobianos/síntese química , Antineoplásicos/síntese química , Peptídeos Penetradores de Células/biossíntese , Hipoglicemiantes/síntese química , Engenharia de Proteínas/métodos , Proteínas Recombinantes de Fusão/biossíntese , Antibacterianos/síntese química , Antibacterianos/uso terapêutico , Fármacos Antiobesidade/síntese química , Fármacos Antiobesidade/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Antineoplásicos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Peptídeos Penetradores de Células/genética , Peptídeos Penetradores de Células/uso terapêutico , Citotoxinas/síntese química , Citotoxinas/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Desenho de Drogas , Humanos , Hipoglicemiantes/uso terapêutico , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Obesidade/fisiopatologia , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/uso terapêutico
10.
Curr Obes Rep ; 8(3): 201-209, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31054014

RESUMO

PURPOSE OF REVIEW: This review describes (1) the clinical assessment of pediatric patients with severe obesity, including a summary of salient biological, psychological, and social factors that may be contributing to the patient's obesity and (2) the current state of treatment strategies for pediatric severe obesity, including lifestyle modification therapy, pharmacotherapy, and metabolic and bariatric surgery. RECENT FINDINGS: Lifestyle modification therapy alone is insufficient for achieving clinically significant BMI reduction for most youth with severe obesity and metabolic and bariatric surgery, though effective and durable, is not a scalable treatment strategy. Pharmacological agents in the pipeline may 1 day fill this gap in treatment. Treatment of severe pediatric obesity requires a chronic care management approach utilizing multidisciplinary teams of health care providers and multi-pronged therapies.


Assuntos
Obesidade Mórbida/terapia , Obesidade Pediátrica/terapia , Adolescente , Fármacos Antiobesidade/uso terapêutico , Cirurgia Bariátrica/métodos , Terapia Comportamental/métodos , Índice de Massa Corporal , Criança , Dieta , Exercício , Pessoal de Saúde , Humanos , Estilo de Vida , Determinação de Necessidades de Cuidados de Saúde , Obesidade Mórbida/psicologia , Obesidade Pediátrica/psicologia , Psicologia , Perda de Peso
11.
Pak J Pharm Sci ; 32(2): 709-720, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31081787

RESUMO

Enzymes are biological catalyst involve in different biochemical reactions. But over activation of these biomolecules can cause disease thus different inhibitors and knockout therapies are use in current clinical practice. Carbonic anhydrases (CAs), a group of ubiquitously expressed metalloenzymes, are involved in numerous physiological and pathological processes, including gluconeogenesis, lipogenesis, ureagenesis, tumorigenicity and the growth and virulence of various pathogens. In addition to the established role of CA inhibitors (CAIs) as diuretics and antiglaucoma drugs, it has recently emerged that CAIs could have potential as novel anti-obesity, anticancer and anti-infective drugs. Furthermore, recent studies suggest that CA activation may provide a novel therapy for Alzheimer's disease. This article discusses the biological rationale for the novel uses of inhibitors or activators of CA activity in multiple diseases, and highlights progress in the development of specific modulators of the relevant CA isoforms, some of which are now being evaluated in clinical trials.


Assuntos
Anti-Infecciosos/farmacologia , Fármacos Antiobesidade/farmacologia , Antineoplásicos/farmacologia , Inibidores da Anidrase Carbônica/farmacologia , Diuréticos/farmacologia , Doença de Alzheimer/tratamento farmacológico , Animais , Anti-Infecciosos/química , Anti-Infecciosos/uso terapêutico , Fármacos Antiobesidade/química , Fármacos Antiobesidade/uso terapêutico , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Inibidores da Anidrase Carbônica/química , Inibidores da Anidrase Carbônica/uso terapêutico , Diuréticos/química , Diuréticos/uso terapêutico , Glaucoma/tratamento farmacológico , Humanos , Simulação de Acoplamento Molecular , Obesidade/tratamento farmacológico , Osteoporose/tratamento farmacológico
12.
J Ethnopharmacol ; 240: 111943, 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31075382

RESUMO

Ethnopharmacologic relevance: Gyeongshingangjeehwan 18 (GGEx18) is a polyherbal composition derived from Ephedra sinica Stapf (Ephedraceae), Laminaria japonica Aresch (Laminariaceae), and Rheum palmatum L. (Polygonaceae) that is used as an antiobesity drug in Korean clinics. Its constituents are traditionally known to combat obesity, dyslipidemia, and insulin resistance. OBJECTIVE: This study was undertaken to investigate the effects of GGEx18 on glucose metabolism and pancreatic steatosis in obese C57BL/6 J mice fed a high-fat diet (HFD) and to examine the related cellular and molecular mechanisms. MATERIALS AND METHODS: The mice were grouped and fed for 13 weeks as follows: 1) low-fat diet, 2) HFD, or 3) HFD supplemented with GGEx18 (500 mg/kg/day). Various factors affecting insulin sensitivity and pancreatic function were then assessed via blood analysis, histology, immunohistochemistry, and real-time polymerase chain reaction. RESULTS: GGEx18 treatment of obese mice reduced body weight, total fat, and visceral fat mass. GGEx18 inhibited hyperglycemia and hyperinsulinemia and improved glucose and insulin tolerance. GGEx18 also decreased serum leptin levels and concomitantly increased adiponectin levels. Furthermore, GGEx18-treated mice exhibited reduced pancreatic fat accumulation and normalized insulin-secreting ß-cell area. GGEx18 increased pancreatic expression of genes promoting fatty acid ß-oxidation (i.e., MCAD and VLCAD), whereas expression levels of lipogenesis-related genes (i.e., PPARγ, SREBP-1c, and FAS) declined. DISCUSSION AND CONCLUSION: GGEx18 curtailed impaired glucose metabolism and pancreatic steatosis in our mouse model by regulating pancreatic genes that govern lipid metabolism and improving insulin sensitivity. This composition may benefit patients with impaired glucose tolerance, insulin resistance, and pancreatic dysfunction.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Intolerância à Glucose/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Obesidade/tratamento farmacológico , Pancreatopatias/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Preparações de Plantas/uso terapêutico , Animais , Fármacos Antiobesidade/farmacologia , Dieta Hiperlipídica , Expressão Gênica/efeitos dos fármacos , Intolerância à Glucose/metabolismo , Hipoglicemiantes/farmacologia , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Pancreatopatias/metabolismo , Extratos Vegetais/farmacologia , Preparações de Plantas/farmacologia
13.
Phytother Res ; 33(7): 1815-1826, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31141276

RESUMO

Capsaicinoid nonivamide (PAVA) and rosuvastatin (RSV) have been shown to exert antioxidant and anti-obesity effects in various animal models, but it is unknown whether their combination would be an effective treatment for obesity-related endothelial dysfunction. This study aimed to investigate the mechanism of PAVA in synergy with RSV. Male Sprague-Dawley rats were given a high-fat diet (HFD) or normal diet during a 20-week period. At 16 weeks, rats in each diet group were divided into subgroups. Normal diet rats were divided into Normal diet control, Normal diet with PAVA, and Normal diet with RSV groups. HFD rats were subdivided into HFD control, HFD with PAVA, HFD with RSV, and HFD with PAVA + RSV groups and evaluated for metabolic parameters, blood pressure, aortic function, and histological change of the aorta in rats. Our results showed the combined therapy had a significantly greater effect than the monotherapy in all measured parameters; this was indicated by improvement in insulin sensitivity and aortic function, decreased blood pressure, lower oxidative stress, and prevention of vascular damage. The synergistic effect of the PAVA and RSV can protect HFD-induced obesity-related endothelial dysfunction, suggesting that the combination of PAVA and RSV could be an effective alternative treatment for obesity-related complications in patients with cardiovascular disease.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Capsaicina/análogos & derivados , Obesidade/tratamento farmacológico , Rosuvastatina Cálcica/uso terapêutico , Animais , Aorta/efeitos dos fármacos , Aorta/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Capsaicina/uso terapêutico , Dieta Hiperlipídica , Sinergismo Farmacológico , Quimioterapia Combinada , Resistência à Insulina , Masculino , Obesidade/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley
14.
Nutrients ; 11(4)2019 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-31013725

RESUMO

Obesity is a serious public health issue in developed countries, and is known to increase the risk of several diseases such as diabetes, cardiovascular events and arteriosclerosis. These phenomena are closely correlated with oxidative damage. Recently, several lines of evidence have demonstrated that neurodegenerative diseases such as Alzheimer's and Parkinson's are also related to oxidative damage. To clarify the relationship between obesity and oxidative brain injury, we investigated brain antioxidant networks in high-fat (HF) diet-treated mice in the presence or absence of tocotrienols (T3s) and bran. Co-treatment with T3s and bran significantly inhibited bodyweight gain in HF diet-treated mice. Serum and cortex T3 levels, and brain antioxidant enzyme activities and protein expressions did not differ among the groups except for SOD protein expression in the cerebellum. Brain p-mTOR and p-Akt protein expressions, which are related to autophagy, did not differ among the groups. These results indicate that treatment with T3s for eight weeks had showed an anti-obesity effect in HF diet-treated mice. However, significant alterations in T3 levels were not observed in the serum and brain of mice.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Antioxidantes/uso terapêutico , Encéfalo/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Fibras na Dieta/uso terapêutico , Obesidade/prevenção & controle , Tocotrienóis/uso terapêutico , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Encéfalo/metabolismo , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/efeitos adversos , Fibras na Dieta/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Doenças Neurodegenerativas/metabolismo , Obesidade/etiologia , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Tocotrienóis/metabolismo , Tocotrienóis/farmacologia , Ganho de Peso/efeitos dos fármacos
15.
Diab Vasc Dis Res ; 16(2): 128-132, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-31014100

RESUMO

Insulin resistance has a broad pathogenic impact affecting metabolic, cardio-renal and other disease areas. Extensive studies to dissect the mechanisms of insulin resistance have provided valuable insights to shape current clinical awareness and advance therapeutic practice. However, the development of direct interventions against insulin resistance has been hindered by its complex and highly variable presentations, especially in type 2 diabetes. Among glucose-lowering agents, metformin and thiazolidinediones provide cellular actions that counter some effects of insulin resistance: reduced glucotoxicity and weight-lowering with antidiabetic therapies also improve insulin action, except that endogenously- or exogenously-created hyperinsulinaemia may partially compromise these benefits. Increasing awareness of the pervasiveness and damaging ramifications of insulin resistance heightens the need for more specifically targeted and more effective therapies.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Insulina/uso terapêutico , Animais , Fármacos Antiobesidade/uso terapêutico , Biomarcadores/sangue , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Descoberta de Drogas/métodos , Humanos , Hipoglicemiantes/efeitos adversos , Incretinas/uso terapêutico , Insulina/efeitos adversos , Insulina/sangue , Fatores de Risco , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Resultado do Tratamento
16.
Nutrients ; 11(4)2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30995824

RESUMO

Supplementation with inulin-propionate ester (IPE), which delivers propionate to the colon, suppresses ad libitum energy intake and stimulates the release of satiety hormones acutely in humans, and prevents weight gain. In order to determine whether IPE remains effective when incorporated into food products (FP), IPE needs to be added to a widely accepted food system. A bread roll and fruit smoothie were produced. Twenty-one healthy overweight and obese humans participated. Participants attended an acclimatisation visit and a control visit where they consumed un-supplemented food products (FP). Participants then consumed supplemented-FP, containing 10 g/d inulin or IPE for six days followed by a post-supplementation visit in a randomised crossover design. On study visits, supplemented-FP were consumed for the seventh time and ad libitum energy intake was assessed 420 min later. Blood samples were collected to assess hormones and metabolites. Resting energy expenditure (REE) was measured using indirect calorimetry. Taste and appearance ratings were similar between FP. Ad libitum energy intake was significantly different between treatments, due to a decreased intake following IPE-FP. These observations were not related to changes in blood hormones and metabolites. There was an increase in REE following IPE-FP. However, this effect was lost after correcting for changes in fat free mass. Our results suggest that IPE suppresses appetite and may alter REE following its incorporation into palatable food products.


Assuntos
Apetite/efeitos dos fármacos , Metabolismo Basal/efeitos dos fármacos , Suplementos Nutricionais , Manipulação de Alimentos , Inulina/farmacologia , Obesidade , Propionatos/farmacologia , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/uso terapêutico , Calorimetria Indireta , Colo , Estudos Cross-Over , Método Duplo-Cego , Ingestão de Energia/efeitos dos fármacos , Feminino , Hormônios/sangue , Humanos , Inulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Obesidade/dietoterapia , Obesidade/metabolismo , Obesidade/fisiopatologia , Sobrepeso , Propionatos/uso terapêutico , Descanso , Resposta de Saciedade/efeitos dos fármacos , Paladar
17.
Wien Klin Wochenschr ; 131(Suppl 1): 71-76, 2019 May.
Artigo em Alemão | MEDLINE | ID: mdl-30980154

RESUMO

For several years obesity and type 2 diabetes have been increasingly summarized under the name "diabesity". This is due to the fact that in most cases obesity precedes diabetes and is the most important risk factor for the worldwide increase of type 2 diabetes. The body mass index (BMI) is a very crude measure of body fatness in individuals. Even normal weight persons can have too much body fat in cases of a lack of muscle mass (sarcopenia), which is why additional measurements of waist circumference and body fatness, e. g. bioimpedance analysis (BIA), are recommended. Lifestyle management including nutrition modification and increase in physical activity are important measures for the prevention and treatment of diabetes. Regarding the treatment of type 2 diabetes, body weight is increasingly used as a secondary target parameter. The choice of anti-diabetic treatment and also concomitant treatment is increasingly influenced by body weight. The significance of anti-obesity medications in the treatment of type 2 diabetes will have to be clarified by future studies with body weight as the primary endpoint. Bariatric surgery is at present indicated with a BMI >35 kg/m2 with concomitant risk factors, such as diabetes and can lead at least to partial diabetes remission but has to be incorporated into an appropriate lifelong care concept.


Assuntos
Diabetes Mellitus Tipo 2 , Obesidade , Fármacos Antiobesidade/uso terapêutico , Cirurgia Bariátrica , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Humanos , Obesidade/epidemiologia , Obesidade/prevenção & controle , Guias de Prática Clínica como Assunto , Circunferência da Cintura
18.
Int J Mol Sci ; 20(7)2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30939798

RESUMO

Brown adipose tissue (BAT), an organ that burns energy through uncoupling thermogenesis, is a promising therapeutic target for obesity. However, there are still no safe anti-obesity drugs that target BAT in the market. In the current study, we performed large scale screening of 636 compounds which were approved by Food and Drug Administration (FDA) to find drugs that could significantly increase uncoupling protein 1 (UCP1) mRNA expression by real-time PCR. Among those UCP1 activators, most of them were antibiotics or carcinogenic compounds. We paid particular attention to fluvastatin sodium (FS), because as an inhibitor of the cellular hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase, FS has already been approved for treatment of hypercholesteremia. We found that in the cellular levels, FS treatment significantly increased UCP1 expression and BAT activity in human brown adipocytes. Consistently, the expression of oxidative phosphorylation-related genes was significantly increased upon FS treatment without differences in adipogenic gene expression. Furthermore, FS treatment resisted to high-fat diet (HFD)-induced body weight gain by activating BAT in the mice model. In addition, administration of FS significantly increased energy expenditure, improved glucose homeostasis and ameliorated hepatic steatosis. Furthermore, we reveal that FS induced browning in subcutaneous white adipose tissue (sWAT) known to have a beneficial effect on energy metabolism. Taken together, our results clearly demonstrate that as an effective BAT activator, FS may have great potential for treatment of obesity and related metabolic disorders.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Fármacos Antiobesidade/uso terapêutico , Fluvastatina/uso terapêutico , Obesidade/tratamento farmacológico , Tecido Adiposo Marrom/metabolismo , Animais , Fármacos Antiobesidade/farmacologia , Células Cultivadas , Metabolismo Energético , Fluvastatina/farmacologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
19.
J Ethnopharmacol ; 238: 111843, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-30951844

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hordeum vulgare (L.), commonly known as barley belonging to Poaceae family is a widely used cereal. Barley seeds are considered to possess high nutritional value and antioxidant properties. The grass of barley is also considered as a part of health drink in many parts of India. It is claimed to suppress a number of health disorders including obesity, diabetes, circulatory disorders, arthritis, anemia, excessive cholesterol levels, renal difficulties, and cancer. However, the antiobesity potential of barley grass has not been explored till now. AIM OF THE STUDY: The aim of the present study was to characterize and evaluate the anti-obesity activity of barley grass juice (Hordeum vulgare L.) in high fat diet induced model. MATERIALS AND METHODS: Barley grass juice was characterized by GC-MS analysis for identifying the active phytochemical constituents and was subjected to standard in vitro antioxidant studies. For in vivo studies, obesity was induced by high fat diet model in adult male Wistar rats. Atorvastatin (10 mg/kg) was used as the standard and barley grass juice was administered at two dose levels (200 and 400 mg/kg) for a period of 60 days. Anthropometric parameters, lipid profile and liver function markers were screened at regular intervals in all the treatment groups. At the end of the study, histopathological evaluations of liver and carotid artery were performed. The levels of in vivo antioxidant enzymes like SOD, catalase, reduced glutathione and lipid peroxidation in terms of malondialdehyde were also estimated in the liver homogenates. Expression levels of PPAR-gamma and caspase 3 were determined in the liver. RESULTS: Results indicated that barley grass juice (Hordeum vulgare L.) exhibited potent in vitro antioxidant activity. Rats administered with high fat diet for 60 days showed a significant increase in body weight, BMI, altered lipid profile, liver function markers like AST, ALT, ALP and increased expression of PPAR-gamma and caspase 3. However, administration of barley grass juice for 60 days, profoundly decreased the bodyweight, BMI, improved lipid profile and liver function markers. This was supported by the decreased expression of PPAR-gamma and caspase 3 in liver. Histopathological variations observed in liver and carotid artery of high fat diet group, when treated with BJG showed preserved hepatocytes and reduced atherosclerosis. GC-MS analysis identified the presence of 12 phytochemical constituents in barley grass juice. CONCLUSION: Our study demonstrates the antiobesity activity of barley grass juice and it may be concluded that barley grass juice can be an effective nutraceutical in the management of obesity.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Suplementos Nutricionais , Hordeum , Obesidade/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Animais , Fármacos Antiobesidade/química , Fármacos Antiobesidade/farmacologia , Peso Corporal/efeitos dos fármacos , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/patologia , Caspase 3/metabolismo , Colesterol/sangue , Dieta Hiperlipídica , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Obesidade/metabolismo , PPAR gama/metabolismo , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos Wistar , Triglicerídeos/sangue
20.
J Ethnopharmacol ; 236: 173-182, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-30851371

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cynometra cauliflora Linn. belongs to the Fabaceae family and is known locally in Malaysia as nam-nam. Traditionally, a decoction of the C. cauliflora leaves is used for treating hyperlipidemia and diabetes. AIM OF THE STUDY: This study aims to investigate the anti-obesity and lipid lowering effects of ethanolic extract of C. cauliflora leaves and its major compound (vitexin) in C57BL/6 obese mice induced by high-fat diet (HFD), as well as to further identify the molecular mechanism underlying this action. METHODS AND MATERIAL: Male C57BL/6 mice were fed with HFD (60% fat) for 16 weeks to become obese. The treatment started during the last 8 weeks of HFD feeding and the obese mice were treated with C. cauliflora leaf extract at 200 and 400 mg/kg/day, orlistat (10 mg/kg) and vitexin (10 mg/kg). RESULTS: The oral administration of C. cauliflora (400 and 200 mg/kg) and vitexin significantly reduced body weight, adipose tissue and liver weight and lipid accumulation in the liver compared to control HFD group. Both doses of C. cauliflora also significantly (P ≤ 0.05) decreased serum triglyceride, LDL, lipase, IL-6, peptide YY, resistin levels, hyperglycemia, hyperinsulinemia, and hyperleptinemia compared to the control HFD group. Moreover, C. cauliflora significantly up-regulated the expression of adiponectin, Glut4, Mtor, IRS-1 and InsR genes, and significantly decreased the expression of Lepr in white adipose tissue. Furthermore, C. cauliflora significantly up-regulated the expression of hypothalamus Glut4, Mtor and NF-kB genes. GC-MS analysis of C. cauliflora leaves detected the presence of phytol, vitamin E and ß-sitosterol. Besides, the phytochemical evaluation of C. cauliflora leaves showed the presence of flavonoid, saponin and phenolic compounds. CONCLUSION: This study shows interesting outcomes of C. cauliflora against HFD-induced obesity and associated metabolic abnormalities. Therefore, the C. cauliflora extract could be a potentially effective agent for obesity management and its related metabolic disorders such as insulin resistance and hyperlipidemia.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Dieta Hiperlipídica/efeitos adversos , Fabaceae/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Administração Oral , Animais , Fármacos Antiobesidade/isolamento & purificação , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Citocinas/sangue , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/sangue , Obesidade/metabolismo , Extratos Vegetais/isolamento & purificação , Triglicerídeos/sangue
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