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1.
Phytochemistry ; 171: 112231, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31901473

RESUMO

Daphne giraldii Nitsche., a member of the genus Daphne (Thymelaeaceae), is a deciduous shrub with mild toxicity. Its rhizome bark, generally called 'Zushima' in Chinese, has many medicinal folkloric uses and good therapeutic effects. Previous studies investigating the chemical constituents and pharmacological activities of D. giraldii have focused on several major classes of compounds, such as coumarins, lignans and flavonoids, especially the interesting enantiomeric flavans. Extracts and pure compounds of D. giraldii were found to possess anti-inflammatory, anti-nociceptive, cytotoxicity, antimalarial, immunomodulating, sedative and hypnotic effects. They have also been reported to influence the cardiovascular functions and blood activities. This comprehensive review will describe the advances in the phytochemistry, pharmacology, medicinal uses and clinical applications of D. giraldii and its formulations covering the literature published from 1970 to 2018. Almost half of the reviewed studies were originally published in non-English languages (mainly in Chinese). Collectively, the aim of this article is to open new avenues for further in-depth pharmacological studies on D. giraldii.


Assuntos
Compostos Fitoquímicos/farmacologia , Thymelaeaceae/química , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Anti-Inflamatórios não Esteroides/farmacologia , Fármacos Antiobesidade/química , Fármacos Antiobesidade/isolamento & purificação , Fármacos Antiobesidade/farmacologia , Antimaláricos/química , Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Humanos , Hipnóticos e Sedativos/química , Hipnóticos e Sedativos/isolamento & purificação , Hipnóticos e Sedativos/farmacologia , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação
2.
PLoS One ; 15(1): e0227637, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31929574

RESUMO

Leptin resistance and co-existing insulin resistance is considered as hallmark of diet-induced obesity. Here, we investigated therapeutic potential of hesperidin to improve leptin and insulin resistance using high fat diet (HFD)-induced obese experimental animal model. We also performed in silico studies to validate therapeutic effectiveness of hesperidin by performing protein-ligand docking and molecular dynamics simulation studies. Group 1 was identified as control group receiving vehicle only. Group 2 was marked as non-treated group receiving 60% HFD. While, other groups were treated daily with orlistat (120 mg/kg/d), hesperidin (55 mg/kg/d), combination of hesperidin (55 mg/kg/d) + orlistat (120 mg/kg/d). Hesperidin alone (P<0.001) and particularly in combination with orlistat (P<0.001), resulted in controlling the levels of HFD-altered biomarkers including random and fasting state of glycemia, leptin and insulin resistance. Similarly, hesperidin also improved the serum and tissue levels of leptin, interleukin-6 and tumor necrosis factor-alpha more significantly (P<0.05) when compared with that of orlistat. These results were found to be in accordance with the results of histopathological examination of pancreas, liver and adipose tissues. In-silico studies also proved that hesperidin binds to leptin receptor with higher affinity as compared to that of orlistat and induces the favorable variations in geometrical conformation of leptin receptor to promote its association with leptin which may lead to the cascades of reactions culminating the lipolysis of fats that may ultimately lead to cure obesity. The results of this study may be a significant expectation among the forthcoming treatment strategies for leptin and insulin resistance.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Fármacos Antiobesidade/farmacologia , Hesperidina/farmacologia , Inflamação/tratamento farmacológico , Resistência à Insulina , Obesidade/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/química , Fármacos Antiobesidade/química , Dieta Hiperlipídica , Modelos Animais de Doenças , Quimioterapia Combinada , Hesperidina/química , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/metabolismo , Hiperlipidemias/patologia , Inflamação/metabolismo , Inflamação/patologia , Leptina/metabolismo , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Obesidade/metabolismo , Obesidade/patologia , Orlistate/química , Orlistate/farmacologia , Ratos Wistar
3.
Food Chem ; 313: 126156, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31931426

RESUMO

Low calorie foods are products designed to replace complete meals or to control snacking in many hypocaloric diets. These products provide many nutrients to the human diet, but little is known about their mineral elements composition. Here we study the mineral profile of weight loss related products, including the analysis of 22 elements (As, Ba, Be, Bi, Cd, Co, Cr, Cu, K, Mn, Mo, Na, Ni, P, Pb, Th, Tl, Sb, U, V, Y and Zn) in 73 commercial products marketed in Spain. In general a portion of these products provide up to 20-30% of the daily dietary reference intake of essential trace minerals like Cr or Mo. On the contrary, some of these foods have large concentrations of toxic minerals like As, Cd or Pb. In fact, the intake of those products with higher concentrations of toxic elements during a weight loss program could pose a risk to human health.


Assuntos
Fármacos Antiobesidade/química , Dieta Redutora , Contaminação de Alimentos/análise , Minerais/análise , Fármacos Antiobesidade/análise , Análise de Alimentos , Humanos , Metais/análise , Nível de Efeito Adverso não Observado , Medição de Risco , Espanha , Oligoelementos/análise
4.
J Agric Food Chem ; 68(1): 4-16, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31829005

RESUMO

Obesity has an important influence on health conditions, causing a multitude of complications and comorbidities, and drug therapy is considered to be one of the treatment strategies. Nowadays, there is increasing interest in the study of intestinal microbiota regulation of obesity; also, an increasing number of agricultural and sideline products have been found to have anti-obesity potential. In the present review, we summarize an overview of current known and potential anti-obesity oligosaccharides and their molecular structures. We describe their anti-obesity potential activity and the molecular structure associated with this activity, the regulation of intestinal microbiota composition and its mechanism of action, including regulation of the short-chain fatty acid (SCFA) pathway and altering bile acid (BA) pathway. This review will provide new ideas for us to develop new anti-obesity functional foods.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Obesidade/tratamento farmacológico , Oligossacarídeos/administração & dosagem , Animais , Fármacos Antiobesidade/química , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal , Humanos , Obesidade/metabolismo , Obesidade/microbiologia , Oligossacarídeos/química , Prebióticos/administração & dosagem , Prebióticos/análise
5.
J Nanobiotechnology ; 17(1): 122, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842876

RESUMO

Obesity through its association with type 2 diabetes (T2D), cancer and cardiovascular diseases (CVDs), poses a serious health threat, as these diseases contribute to high mortality rates. Pharmacotherapy alone or in combination with either lifestyle modification or surgery, is reliable in maintaining a healthy body weight, and preventing progression to obesity-induced diseases. However, the anti-obesity drugs are limited by non-specificity and unsustainable weight loss effects. As such, novel and improved approaches for treatment of obesity are urgently needed. Nanotechnology-based therapies are investigated as an alternative strategy that can treat obesity and be able to overcome the drawbacks associated with conventional therapies. The review presents three nanotechnology-based anti-obesity strategies that target the white adipose tissues (WATs) and its vasculature for the reversal of obesity. These include inhibition of angiogenesis in the WATs, transformation of WATs to brown adipose tissues (BATs), and photothermal lipolysis of WATs. Compared to conventional therapy, the targeted-nanosystems have high tolerability, reduced side effects, and enhanced efficacy. These effects are reproducible using various nanocarriers (liposomes, polymeric and gold nanoparticles), thus providing a proof of concept that targeted nanotherapy can be a feasible strategy that can combat obesity and prevent its comorbidities.


Assuntos
Fármacos Antiobesidade/química , Portadores de Fármacos/química , Nanopartículas/química , Obesidade/tratamento farmacológico , Indutores da Angiogênese/metabolismo , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Animais , Fármacos Antiobesidade/farmacologia , Liberação Controlada de Fármacos , Ouro/química , Humanos , Lipídeos/química , Polímeros/química , Nanomedicina Teranóstica , Resultado do Tratamento
6.
Pak J Pharm Sci ; 32(4): 1723-1747, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31608897

RESUMO

Curcumin, a natural polyphenolic compound derived from turmeric (Curcuma longa L), has proven to exhibit biological activity towards different kinds of diseases. But the low oral bioavailability results in a limited application in clinic treatment. Recently, numerous curcumin derivatives were synthesized by the modification of three important functional groups: The aromatic o-methoxy phenolic group, a seven conjugated carbon linker and the ß-diket one moiety. However, many people know curcumin only as an anticancer agent and overlook the diverse biological activities of curcumin and curcumin-based derivatives. In this article, we summarized the novel synthetic curcuminoids by different therapeutic activities including antioxidant activity, anti-HIV activity, stimulating activity of gastric emptying, anti-inflammatory activity, ACE inhibition activity, prevention of Parkinson's disease, anti-parasitism, anti-obesity, prevention of Alzheimer's disease, and antibacterial activity. The relation between structural features and activities were also investigated.


Assuntos
Fármacos Anti-HIV/farmacologia , Antioxidantes/farmacologia , Antiparkinsonianos/farmacologia , Diarileptanoides/farmacologia , Doença de Alzheimer/tratamento farmacológico , Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Fármacos Anti-HIV/química , Fármacos Antiobesidade/química , Fármacos Antiobesidade/farmacologia , Antioxidantes/química , Antiparkinsonianos/química , Antiprotozoários/química , Antiprotozoários/farmacologia , Diarileptanoides/síntese química , Diarileptanoides/química , Esvaziamento Gástrico/efeitos dos fármacos , Humanos , Estrutura Molecular
7.
Chem Biodivers ; 16(10): e1900347, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31532890

RESUMO

Catechins in green tea are well-known to be effective in reducing the risk of obesity. The purpose of this study was to elucidate the effects of catechins present in green tea on adipocyte differentiation and mature adipocyte metabolism. Treatment of 3T3-L1 mouse adipocyte during differentiation adipocytes with (-)-epigallocatechin (EGC) and gallic acid (GA) resulted in dose-dependent inhibition of adipogenesis. Specifically, EGC increased adiponectin and uncoupling protein 1 (UCP1) transcription in mature adipocytes. Transcription levels of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) were not significantly impacted by either of the compounds. These results suggest that the EGC is the most effective catechin having anti-obesity activity. Finally, EGC is an attractive candidate component for remodeling obesity.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Catequina/análogos & derivados , Células 3T3-L1 , Tecido Adiposo Marrom/metabolismo , Animais , Fármacos Antiobesidade/química , Fármacos Antiobesidade/isolamento & purificação , Catequina/química , Catequina/isolamento & purificação , Catequina/farmacologia , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Camundongos , Estrutura Molecular , Relação Estrutura-Atividade , Chá/química
8.
Mar Drugs ; 17(9)2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31533255

RESUMO

Obesity and its related complications have become one of the leading problems affecting human health. However, current anti-obesity treatments are limited by high cost and numerous adverse effects. In this study, we investigated the use of a non-toxic green food additive, known as unsaturated alginate oligosaccharides (UAOS) from the enzymatic degradation of Laminaria japonicais, which showed effective anti-obesity effects in a high-fat diet (HFD) mouse model. Compared with acid hydrolyzed saturated alginate oligosaccharides (SAOS), UAOS significantly reduced body weight, serum lipid, including triacylglycerol (TG), total cholesterol (TC) and free fatty acids (FFA), liver weight, liver TG and TC, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels, adipose mass, reactive oxygen species (ROS) formation, and accumulation induced in HFD mice. Moreover, the structural differences in ß-d-mannuronate (M) and its C5 epimer α-l-guluronate (G) did not cause significant functional differences. Meanwhile, UAOS significantly increased both AMP-activated protein kinase α (AMPKα) and acetyl-CoA carboxylase (ACC) phosphorylation in adipocytes, which indicated that UAOS had an anti-obesity effect mainly through AMPK signaling. Our results indicate that UAOS has the potential for further development as an adjuvant treatment for many metabolic diseases such as fatty liver, hypertriglyceridemia, and possibly diabetes.


Assuntos
Alginatos/administração & dosagem , Fármacos Antiobesidade/administração & dosagem , Aditivos Alimentares/administração & dosagem , Obesidade/dietoterapia , Oligossacarídeos/administração & dosagem , Proteínas Quinases Ativadas por AMP/metabolismo , Acetil-CoA Carboxilase/metabolismo , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Alginatos/química , Ração Animal , Animais , Fármacos Antiobesidade/química , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Aditivos Alimentares/química , Humanos , Masculino , Camundongos , Obesidade/etiologia , Oligossacarídeos/química , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento
9.
Forensic Sci Int ; 303: 109932, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31473560

RESUMO

With the increasing prevalence of obesity, the use of counterfeit drugs for weight loss is widespread owing to their easy and rapid availability. Since counterfeit weight-loss drugs are not prepared under the rigorous standard of Good Manufacturing Practice (GMP), they pose a risk to public health and cause significant side effects. To counteract the risk posed by counterfeit drugs, we investigated counterfeit weight-loss drugs seized by the Incheon Customs Services using UHPLC-PDA. Five of 23 confiscated samples with distinctive pink-coloured coating contained levothyroxine, sennoside A and B, and phenolphthalein in amounts ranging from 0.03-132.40 mg/g. In addition, three unknown compounds in one of the adulterated samples containing phenolphthalein were structurally elucidated by several analytical techniques. Their accurate masses corresponded to molecular formula of C34H22O7, C34H20O6, and C20H12O3, respectively. These compounds were identified as impurities, possibly produced during the synthesis of phenolphthalein or by improper removal during purification. These impurities were detected for the first time in counterfeit drugs.


Assuntos
Fármacos Antiobesidade/química , Medicamentos Falsificados/química , Cromatografia Líquida de Alta Pressão , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular
10.
BMC Complement Altern Med ; 19(1): 246, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488172

RESUMO

BACKGROUND: Yangkyuksanwha-tang (YST) is an herbal medicine based on Sasang constitutional medicine (SCM) and is widely used in Korean traditional medicine. The aim of the study was to evaluate the effect of YST on obesity in high-fat diet (HFD)-induced obese mice. METHODS: We induced obesity in C57bl/6 J mice using a HFD, and then orally administered 300 mg/kg YST for 6 weeks. We measured body weight, food efficiency, organ and fat weight, serum biochemical parameters, and obesity-related gene expression, and carried out histological analysis at the end of the experimental period. RESULTS: YST significantly reduced the absolute body weight and food efficiency ratio. The serum, aminotransferase, glucose, total cholesterol, triglyceride, and low-density lipoprotein-cholesterol levels were significantly lower in the YST-treated group than in the control group, whereas the high-density lipoprotein-cholesterol level in the YST-treated group was significantly higher. The YST-treated group also showed a significant reduction in regional fatty tissues and the absolute weight of various organs. We also observed a significantly reduced expression of AP2/FABP4, C/EBP-ß, leptin, and SREBP1c/ADD1 mRNA, and significantly increased expression of UCP-2 and adiponectin mRNA in adipose tissue in the YST-treated group. YST also decreased the lipid droplet size and lipid accumulation in the liver, as well as adipocyte size in epididymal adipose tissue. At the dose tested, YST was non-toxic to the liver and kidneys of the mice. CONCLUSION: The results imply that YST has anti-obesity effects in obesity-induced mice. Although the number of experimental animals was limited and the drug effects concern mice, rather than humans, which have different constitutions, the study has valuable implications with respect to the general effects of YST.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Obesidade/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Animais , Fármacos Antiobesidade/química , Peso Corporal/efeitos dos fármacos , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , HDL-Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Humanos , Leptina/genética , Leptina/metabolismo , Masculino , Medicina Tradicional Coreana , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/genética , Obesidade/metabolismo , Obesidade/fisiopatologia , Extratos Vegetais/química , Plantas Medicinais/química , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
11.
Phytomedicine ; 64: 153075, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31476558

RESUMO

BACKGROUND: Obesity is one of the major health problems worldwide. The induction of brown adipocyte formation and activity represents a promising therapeutic option by increasing energy expenditure. Asian herbs have the potential to treat obesity, however, pharmacological effects should be well documented at the molecular level first. HYPOTHESIS: A novel hypothesis-driven screening approach identified the root of Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep (PLR) to have potential effects on obesity by stimulating brown adipocytes. STUDY DESIGN: This study explored the metabolic effects of PLR water extract (PLRE) in a high-fat diet-induced obesity mouse model and characterized its secondary metabolite composition. METHODS: Animals were orally treated daily for two weeks and the bioactivity of PLRE evaluated by measuring various parameters including body weight, circulating metabolites, energy expenditure and insulin sensitivity. The chemical composition of the mains components was obtained by HPLC-MS-ELSD-PDA. Based on the dereplication results and semi-quantitative estimation, pure molecules were selected for tests on adipocytes in vitro. RESULTS: PLRE induces brown adipocyte activity and triggers the formation of brown-like cells in inguinal fat tissue, weight loss, and improved glucose metabolism. These effects are primarily caused by cell-autonomous activation of brown adipocytes and not by autonomic nervous system regulation. Even though the analysis of PLRE revealed puerarin as the most abundant secondary metabolite, it showed no effect on brown adipocyte formation and function. Brown adipocyte activity was induced dose-dependently by two other isoflavones, daidzein, and genistein. Daidzein is present in a very small amount in PLRE, but various glycosidic isoflavones, including puerarin, may release daidzein after metabolism. CONCLUSION: This approach demonstrated the positive effects of PLRE on a diet-induced obesity mouse model and provided clues on the mode of action of PLRE at the molecular level.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Obesidade/tratamento farmacológico , Pueraria/química , Adipócitos/efeitos dos fármacos , Adipócitos Marrons/efeitos dos fármacos , Adipócitos Marrons/metabolismo , Animais , Fármacos Antiobesidade/química , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético/efeitos dos fármacos , Genisteína/farmacologia , Resistência à Insulina , Isoflavonas/farmacologia , Camundongos , Obesidade/etiologia , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Pueraria/metabolismo
12.
Mar Drugs ; 17(9)2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31540318

RESUMO

This study investigated the anti-obesity effect of a polysaccharide-rich red algae Gelidium amansii hot-water extract (GHE) in high-fat (HF) diet-induced obese hamsters. GHE contained 68.54% water-soluble indigestible carbohydrate polymers. Hamsters were fed with a HF diet for 5 weeks to induce obesity, and then randomly divided into: HF group, HF with 3% guar gum diet group, HF with 3% GHE diet group, and HF with orlistat (200 mg/kg diet) group for 9 weeks. The increased weights of body, liver, and adipose in the HF group were significantly reversed by GHE supplementation. Lower plasma leptin, tumor necrosis factor-α, and interleukin-6 levels were observed in the GHE+HF group compared to the HF group. GHE also increased the lipolysis rate and decreased the lipoprotein lipase activity in adipose tissues. GHE induced an increase in the phosphorylation of AMP-activated protein kinase (AMPK) and the protein expressions of peroxisome proliferator-activated receptor alpha (PPARα) and uncoupling protein (UCP)-2 in the livers. The decreased triglyceride and total cholesterol in the plasma and liver were also observed in obese hamsters fed a diet with GHE. These results suggest that GHE exerts a down-regulation effect on hepatic lipid metabolism through AMPK phosphorylation and up-regulation of PPARα and UCP-2 in HF-induced obese hamsters.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Suplementos Nutricionais , Obesidade/dietoterapia , Extratos Vegetais/administração & dosagem , Rodófitas/química , Adenilato Quinase/metabolismo , Animais , Fármacos Antiobesidade/química , Fármacos Antiobesidade/isolamento & purificação , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Mesocricetus , Obesidade/etiologia , Orlistate/administração & dosagem , Fosforilação/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Transdução de Sinais/efeitos dos fármacos , Proteína Desacopladora 2/metabolismo , Regulação para Cima/efeitos dos fármacos , Água/química
13.
Eur J Med Chem ; 181: 111565, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31387062

RESUMO

The human Carbonic anhydrases (hCA) VA and VB play a key role in ureagenesis, gluconeogenesis, lipogenesis and in the metabolism regulation, thus representing highly popular drug targets. Albeit several hCA inhibitors have been designed and are currently in clinical use, serious drug interactions have been reported due to their poor selectivity. In this perspective, the drug repurposing approach could be a useful tool in order to investigate the drug promiscuity/polypharmacology profile. In this study, virtual screening techniques and in vitro assays were combined to identify novel selective hCA VA inhibitors from among around 94000 compounds. The docking analysis highlighted 12 promising best hits, biologically characterized in terms of their hCA VA inhibitory activity. Interestingly, among them, the anticancer agents fludarabine and lenvatinib and the antiepileptic rufinamide were able to selectively inhibit the enzyme activity in the micromolar range, while a pyrido-indole derivative, the homovanillic acid sulfate and the desacetyl metabolite of the antibacterial cephapirin in the nanomolar range.


Assuntos
Fármacos Antiobesidade/farmacologia , Inibidores da Anidrase Carbônica/farmacologia , Reposicionamento de Medicamentos , Obesidade/tratamento farmacológico , Fármacos Antiobesidade/química , Anidrase Carbônica I/antagonistas & inibidores , Anidrase Carbônica I/metabolismo , Anidrase Carbônica II/antagonistas & inibidores , Anidrase Carbônica II/metabolismo , Inibidores da Anidrase Carbônica/química , Desenho Assistido por Computador , Descoberta de Drogas , Humanos , Simulação de Acoplamento Molecular , Obesidade/metabolismo
14.
Z Naturforsch C J Biosci ; 74(9-10): 265-273, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31150363

RESUMO

This study was performed to isolate antiobesity components from the crude extract of Portulaca oleracea. The crude extract was partitioned into n-hexane, 85% aqueous methanol, n-butanol, and water fractions. Their effects on adipogenic differentiation were evaluated in 3T3-L1 cells. Among the solvent fractions from P. olearacea, the 85% aq. MeOH effectively reduced the levels of lipid accumulation. Further purification of 85% aq. MeOH led to the isolation of the known homoisoflavonoids 1-4, as the active substances. The administration of homoisoflavonoids to adipocyte cells decreased the lipid accumulation and glucose consumption and increased the release of glycerol into culture medium. In particular, homoisoflavonoid 3 effectively down-regulated the adipogenic transcription genes such as peroxisome proliferator activated receptor-γ (PPARγ) and CCAAT/enhancer-binding proteins (C/EBPα), and adipogenic target genes such as fatty acid binding protein 4 (FABP4), fatty acid transport protein 1 (FATP1), and acyl-CoA synthase 1 (ACS1).


Assuntos
Adipócitos/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Isoflavonas/farmacologia , Extratos Vegetais/farmacologia , Portulaca/química , Células 3T3 , Adipócitos/metabolismo , Animais , Fármacos Antiobesidade/química , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Coenzima A Ligases/metabolismo , Proteínas de Transporte de Ácido Graxo/metabolismo , Proteínas de Ligação a Ácido Graxo/metabolismo , Glucose/metabolismo , Glicerol/metabolismo , Isoflavonas/química , Metabolismo dos Lipídeos , Camundongos , PPAR gama/metabolismo , Extratos Vegetais/química
15.
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
16.
Eur J Pharm Sci ; 135: 1-11, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31067495

RESUMO

Obesity is a rapidly growing epidemic, with over one-third of the global population classified as overweight or obese. Consequently, an urgent need exists to develop innovative approaches and technologies that regulate energy uptake, to curb the rising trend in obesity statistics. In this study, nanostructured clay (NSC) particles, fabricated by spray drying delaminated dispersions technologies that regulate energy uptake, to curb the rising trend in obesity statistics. In this study, nanostructured clay (NSC) particles, fabricated by spray drying delaminated dispersions of commercial clay platelets (Veegum® HS and LAPONITE® XLG), were delivered as complimentary, bioactive excipients with the potent lipase inhibitor, orlistat, for the inhibition of fat (lipid) hydrolysis. Simulated intestinal lipolysis studies were performed by observing changes in free fatty acid concentration and revealed that a combinatorial effect existed when NSC particles were co-administered with orlistat, as evidenced by a 1.2- to 1.6-fold greater inhibitory response over 60 min, compared to dosing orlistat alone. Subsequently, it was determined that a multifaceted approach to lipolysis inhibition was presented, whereby NSC particles adsorbed high degrees of lipid (up to 80% of all lipid species present in lipolysis media) and thus physically shielded the lipid-in-water interface from lipase access, while orlistat covalently attached and blocked the lipase enzyme active site. Thus, the ability for NSC particles to enhance the biopharmaceutical performance and potency of orlistat is hypothesised to translate into promising in vivo pharmacodynamics, where this novel approach is predicted to lead to considerably greater weight reductions for obese patients, compared to dosing orlistat alone.


Assuntos
Fármacos Antiobesidade/química , Argila/química , Lipase/antagonistas & inibidores , Lipídeos/química , Nanopartículas/química , Obesidade/tratamento farmacológico , Orlistate/química , Compostos de Alumínio/química , Fármacos Antiobesidade/administração & dosagem , Suplementos Nutricionais , Digestão , Ácidos Graxos/metabolismo , Humanos , Hidrólise , Absorção Intestinal , Lipase/química , Lipólise , Compostos de Magnésio/química , Orlistate/administração & dosagem , Tamanho da Partícula , Silicatos/química , Propriedades de Superfície
17.
Mar Drugs ; 17(5)2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31083362

RESUMO

Obesity is a complex disease resulting in several metabolic co-morbidities and is increasing at epidemic rates. The marine environment is an interesting resource of novel compounds and in particular cyanobacteria are well known for their capacity to produce novel secondary metabolites. In this work, we explored the potential of cyanobacteria for the production of compounds with relevant activities towards metabolic diseases using a blend of target-based, phenotypic and zebrafish assays as whole small animal models. A total of 46 cyanobacterial strains were grown and biomass fractionated, yielding in total 263 fractions. Bioactivities related to metabolic function were tested in different in vitro and in vivo models. Studying adipogenic and thermogenic gene expression in brown adipocytes, lipid metabolism and glucose uptake in hepatocytes, as well as lipid metabolism in zebrafish larvae, we identified 66 (25%) active fractions. This together with metabolite profiling and the evaluation of toxicity allowed the identification of 18 (7%) fractions with promising bioactivity towards different aspects of metabolic disease. Among those, we identified several known compounds, such as eryloside T, leptosin F, pheophorbide A, phaeophytin A, chlorophyll A, present as minor peaks. Those compounds were previously not described to have bioactivities in metabolic regulation, and both known or unknown compounds could be responsible for such effects. In summary, we find that cyanobacteria hold a huge repertoire of molecules with specific bioactivities towards metabolic diseases, which needs to be explored in the future.


Assuntos
Fármacos Antiobesidade/farmacologia , Cianobactérias/química , Obesidade/tratamento farmacológico , Adipócitos Marrons/efeitos dos fármacos , Adipócitos Marrons/fisiologia , Animais , Fármacos Antiobesidade/química , Fármacos Antiobesidade/toxicidade , Cianobactérias/crescimento & desenvolvimento , Cianobactérias/metabolismo , Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Células Hep G2 , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/metabolismo , PPAR gama/metabolismo , Testes de Toxicidade , Proteína Desacopladora 1/metabolismo , Peixe-Zebra
18.
J Med Food ; 22(7): 741-751, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31120370

RESUMO

The prevalence of obesity is expanding rapidly worldwide, making the disease a global burden with limited treatment options. The current obesity drug development trends suggest the possibility of reducing weight and reverse metabolic disturbances of obesity by controlling appetite. In this study, we screened more than 8000 plants from our plant library for the cannabinoid (CB1) receptor antagonists and identified Morus alba as a lead medicinal plant. Kuwanon G and Albanin G were isolated and identified from root-barks of Morus alba with 92% and 96% CB1 receptor ligand binding inhibitory activity, respectively. The bioflavonoid standardized extract was tested in the acute food intake study in rats at oral doses of 250 and 500 mg/kg for its appetite suppression activity. Diet-induced obesity in the C57BL/6J mice was used to evaluate the long-term food intake reduction activity and effect on the weight loss administered orally at 250 and 500 mg/kg for 7 weeks. Statistically significant and dose-dependent reduction in food intake was observed in both acute and long-term studies for the extract. Food intake reductions of 58.6% and 44.8% at 250 mg/kg and 50.1% and 44.3% at 500 mg/kg were observed at 1 and 2 h postfood provision, respectively. A 20% reduction in daily calorie intake was observed in the long-term study. Obese mice treated with the high dose of Morus root-bark extract showed 10.4 g (22.5%) and 7.1 g (16.5%) loss in body weight compared with the vehicle-treated obese animals (at week 7) and baseline, respectively. Statistically significant reductions in biochemical markers and visceral fat deposit were also observed. These results demonstrated that Morus alba extracts enriched in Kuwanon G, and Albanin G could be used alone to control appetite, manage body weight, and improve metabolic syndromes.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Apetite/efeitos dos fármacos , Morus/química , Obesidade/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Plantas Medicinais/química , Animais , Fármacos Antiobesidade/química , Ingestão de Alimentos/efeitos dos fármacos , Flavonoides/administração & dosagem , Flavonoides/análise , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/fisiopatologia , Casca de Planta/química , Extratos Vegetais/química , Raízes de Plantas/química , Ratos , Ratos Sprague-Dawley , Perda de Peso/efeitos dos fármacos
19.
Nutrients ; 11(5)2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31117266

RESUMO

Kappaphycus is a commercially important edible red alga widely cultivated for carrageenan production. Here, we aimed to investigate the anti-obesity mechanism of Kappaphycus alvarezii by comparing the effects of whole seaweed (T), extracted native κ-carrageenan (CGN), and the leftover fraction sans-carrageenan (SCGN) supplementations (5%, w/w) on diet-induced obese C57BL/6J mice. A high-fat diet induced both a raised body fat percentage and serum cholesterol level, increased adipocytes size, abnormal levels of adipocytokines, and promoted gut dysbiosis. Our results showed that, overall, both CGN and SCGN were more effective in reversing obesity and related metabolic syndromes to normal levels than T. Furthermore, these findings suggested that CGN- and SCGN-modulated gut dysbiosis induced by a high-fat diet, which may play an influencing role in adiponectin dysregulation. Our data also showed some evidence that CGN and SCGN have distinct effects on selected genes involved in lipid metabolism. In conclusion, both κ-carrageenan and SCGN have novel anti-obesity potential with possible different mechanisms of action.


Assuntos
Fármacos Antiobesidade/farmacologia , Carragenina/farmacologia , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Rodófitas/química , Adipocinas/metabolismo , Animais , Fármacos Antiobesidade/química , Carragenina/química , Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal , Regulação da Expressão Gênica/efeitos dos fármacos , Metabolismo dos Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Projetos Piloto , Extratos Vegetais/química , Organismos Livres de Patógenos Específicos
20.
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
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