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1.
Molecules ; 26(2)2021 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-33435264

RESUMEN

Diabetes mellitus (DM) is a complex disease which currently affects more than 460 million people and is one of the leading cause of death worldwide. Its development implies numerous metabolic dysfunctions and the onset of hyperglycaemia-induced chronic complications. Multiple ligands can be rationally designed for the treatment of multifactorial diseases, such as DM, with the precise aim of simultaneously controlling multiple pathogenic mechanisms related to the disease and providing a more effective and safer therapeutic treatment compared to combinations of selective drugs. Starting from our previous findings that highlighted the possibility to target both aldose reductase (AR) and protein tyrosine phosphatase 1B (PTP1B), two enzymes strictly implicated in the development of DM and its complications, we synthesised 3-(5-arylidene-4-oxothiazolidin-3-yl)propanoic acids and analogous 2-butenoic acid derivatives, with the aim of balancing the effectiveness of dual AR/PTP1B inhibitors which we had identified as designed multiple ligands (DMLs). Out of the tested compounds, 4f exhibited well-balanced AR/PTP1B inhibitory effects at low micromolar concentrations, along with interesting insulin-sensitizing activity in murine C2C12 cell cultures. The SARs here highlighted along with their rationalization by in silico docking experiments into both target enzymes provide further insights into this class of inhibitors for their development as potential DML antidiabetic candidates.


Asunto(s)
Aldehído Reductasa/antagonistas & inhibidores , Diabetes Mellitus/tratamiento farmacológico , Inhibidores Enzimáticos , Hipoglucemiantes , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Aldehído Reductasa/metabolismo , Animales , Diabetes Mellitus/enzimología , Evaluación Preclínica de Medicamentos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Células Hep G2 , Humanos , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Ligandos , Ratones , Proteína Tirosina Fosfatasa no Receptora Tipo 1/metabolismo , Relación Estructura-Actividad
2.
Int J Nanomedicine ; 16: 297-314, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33488074

RESUMEN

The glucose-sensitive self-adjusting drug delivery system simulates the physiological model of the human pancreas-secreting insulin and then precisely regulates the release of hypoglycemic drugs and controls the blood sugar. Thus, it has good application prospects in the treatment of diabetes. Presently, there are three glucose-sensitive drug systems: phenylboronic acid (PBA) and its derivatives, concanavalin A (Con A), and glucose oxidase (GOD). Among these, the glucose-sensitive polymer carrier based on PBA has the advantages of better stability, long-term storage, and reversible glucose response, and the loading of insulin in it can achieve the controlled release of drugs in the human environment. Therefore, it has become a research hotspot in recent years and has been developed very rapidly. In order to further carry out a follow-up study, we focused on the development process, performance, and application of PBA and its derivatives-based glucose-sensitive polymer drug carriers, and the prospects for the development of this field.


Asunto(s)
Ácidos Borónicos/química , Diabetes Mellitus/tratamiento farmacológico , Portadores de Fármacos/química , Hipoglucemiantes/farmacología , Ácidos Borónicos/metabolismo , Diabetes Mellitus/metabolismo , Portadores de Fármacos/metabolismo , Estudios de Seguimiento , Glucosa/metabolismo , Humanos , Hipoglucemiantes/química , Hipoglucemiantes/uso terapéutico , Insulina/química , Insulina/farmacología , Insulina/uso terapéutico
3.
Food Chem ; 336: 127676, 2021 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-32768902

RESUMEN

Chicory (Cichorium intybus L.) is a perennial herb from the Cichorium genus, Asteraceae family, and is worldwide cultivated. So far, chicory has been used mainly in animal feed, but also in several cases in the food industry: as salad, for teas and tea blends, for coffee supplementation, and as a source for the inulin production. Nowadays there is an increasing interest in chicory utilization for food production and supplementation. Some compounds present in chicory, such as polyphenols, inulin, oligofructose and sesquiterpene lactones may be considered as potential carriers of food functionality. This review describes nutritional, mineral and bioactive composition of the chicory plant and summarized the main biological activities associated with the presence of bioactive compounds in the different plant parts. Finally, the review explores possibilities of uses of chicory and its implementation in food products, with intention to design new functional foods.


Asunto(s)
Achicoria/química , Ingredientes Alimentarios , Fitoquímicos/farmacología , Animales , Antiinfecciosos/química , Antiinfecciosos/farmacología , Humanos , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Valor Nutritivo , Fitoquímicos/química , Extractos Vegetales/efectos adversos , Extractos Vegetales/farmacología
4.
Food Chem ; 339: 128075, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33152868

RESUMEN

Compounds present in broccoli are vulnerable to the digestive process, and encapsulation becomes an alternative for their preservation. The encapsulation of broccoli extract, by electrospraying, was performed with the purpose of evaluating the effect of in vitro simulated digestion on individual compounds and antioxidant and antihyperglycemic potentials. Each digestion fraction was evaluated by chromatography, as well as for antioxidant activity and antihyperglycemic potential. The encapsulated extract showed high encapsulation efficiency and spherical morphology. Losses in the levels of phenolic compounds and glucosinolates were found in both extracts, considering the fractions submitted to digestion. The digestion promoted an increase in the inhibition of hydroxyl, nitric oxide and α-amylase, as well as a decrease in the inhibition of α-glucosidase in both extracts, when compared to undigested fractions. Thus, the digestion affects the compounds content in both encapsulated and unencapsulated extracts. However, they still promote the control of oxidative processes and hyperglycemia.


Asunto(s)
Brassica/química , Digestión , Electricidad , Glucosinolatos/análisis , Fenoles/análisis , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Biomimética , Brassica/metabolismo , Cápsulas , Hiperglucemia , Hipoglucemiantes/química , Hipoglucemiantes/aislamiento & purificación , Hipoglucemiantes/farmacología , Extractos Vegetales/farmacología
5.
Phytomedicine ; 81: 153431, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33352495

RESUMEN

BACKGROUND: Several lines of preclinical studies have shown promising antidiabetic effects of the aqueous leaves extract of Coccinia grandis (Linn.) Voigt (Cucurbitaceae) in vivo and in vitro. PURPOSE: The present study was conducted to evaluate the efficacy and safety of a newly developed herbal formulation of C. grandis in newly diagnosed patients with type 2 diabetes mellitus (T2DM). STUDY DESIGN: A three months long, randomized, double blind, placebo controlled clinical trial in patients with newly diagnosed T2DM. METHOD: Based on fasting plasma glucose (FPG) concentration, a total number of 158 newly diagnosed patients with T2DM (45 ± 15 years age) were recruited for the present trial from the University Medical Clinic, Teaching Hospital, Karapitiya, Galle, Sri Lanka. They were randomly assigned to the test or placebo group to receive 500 mg of herbal drug (n = 79) or placebo drug (n = 79) once daily for three months. Patients and investigators were blinded for the treatment. Percentage of glycated hemoglobin (HbA1C %), insulin and lipid profile parameters were estimated at the base line and at the end of the intervention. Serum concentration of fructosamine was assessed at every other visit of the trial. The homeostatic model assessment for insulin resistance (HOMA-IR), atherogenic index (AI), cardio-protective index (CPI) and coronary risk index (CRI) were calculated. Furthermore, fasting plasma glucose concentration, renal and liver toxicity parameters, hematological parameters, blood pressure (BP) were assessed throughout the study in two weekly intervals till the end of three months. RESULTS: Out of 158, a total number of 145 patients completed the entire clinical trial period successfully. Mean (SD) changes of variables from the baseline to the end of the intervention in test and placebo groups were 0.65 (0.54) and 0.08 (0.66) for HbA1C % (p < 0.001), 1.91 (3.07) and -1.28 (9.77) for insulin (p < 0.001), 0.02 (0.03) and -0.01 (0.04) for frucosamine (p < 0.001), 1.51 (0.49) and 0.05 (0.50) for FPG (p < 0.001), 1.73 (1.36) and -0.37 (3.38) for HOMA-IR (p < 0.001), 0.16 (0.18) and -0.04 (0.42) for TG (p < 0.001), 0.07 (0.08) and -0.02 (0.19) for VLDL-C (p < 0.001), respectively. However, the herbal drug of C. grandis was unable to change other outcome variables significantly when compared to the placebo (p > 0.05). All the renal, liver and toxicity parameters, hematological parameters and BP were within the normal physiological reference ranges at each visit. CONCLUSION: Treatment with herbal drug of C. grandis (500 mg per day) for three months for patients with newly diagnosed T2DM significantly improved their glycemic and selected lipid profile parameters with well tolerated safety.


Asunto(s)
Cucurbitaceae/química , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Adulto , Glucemia/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Diabetes Mellitus Tipo 2/sangre , Método Doble Ciego , Femenino , Hemoglobina A Glucada/análisis , Humanos , Hipoglucemiantes/química , Insulina/sangre , Resistencia a la Insulina , Lípidos/sangre , Masculino , Persona de Mediana Edad , Placebos , Plantas Medicinales/química , Resultado del Tratamiento
6.
Food Chem ; 335: 127645, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32738537

RESUMEN

The dried Ganoderma lucidum (GL) has been widely used for its pharmacological properties and bioactive ganoderic acids (GAs). Herein, extraction procedures combining ultra-sonication and heating were optimized using response surface methodology based on four variables (antioxidant activity, anti-diabetic activity, total GAs content, and total polysaccharide content) and principal component analysis. The extraction of freeze-dried GL at temperatures between 64.2 and 70 °C for 1.2 h maximized the antioxidant activity and GA content, whereas the polysaccharide content and anti-diabetic activity were maximized by extraction between 66.8 and 70 °C for more than 2.8 h. Heat-dried GL extracted at 50 °C for 3 h provided the greatest anti-inflammatory activity against HaCaT cells by suppressing the response to inflammation related cytokines at mRNA levels. These results suggest that extraction conditions might be a limiting factor for target-oriented investigations, and optimized extraction methods may improve the potential effect and quality of harvested GL products.


Asunto(s)
Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Fraccionamiento Químico/métodos , Hipoglucemiantes/aislamiento & purificación , Extractos Vegetales/aislamiento & purificación , Reishi/química , Triterpenos/aislamiento & purificación , Antiinflamatorios/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Línea Celular , Fraccionamiento Químico/instrumentación , Humanos , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Polisacáridos/farmacología , Triterpenos/química , Triterpenos/farmacología
7.
PLoS One ; 15(12): e0240873, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33382706

RESUMEN

BACKGROUND: Sorghum bicolor (SB) is rich in protective phytoconstituents with health benefits and regarded as a promising source of natural anti-diabetic substance. However, its comprehensive bioactive compound(s) and mechanism(s) against type-2 diabetes mellitus (T2DM) have not been exposed. Hence, we implemented network pharmacology to identify its key compounds and mechanism(s) against T2DM. METHODS: Compounds in SB were explored through GC-MS and screened by Lipinski's rule. Genes associated with the selected compounds or T2DM were extracted from public databases, and the overlapping genes between SB-compound related genes and T2DM target genes were identified using Venn diagram. Then, the networking between selected compounds and overlapping genes was constructed, visualized, and analyzed by RStudio. Finally, affinity between compounds and genes was evaluated via molecular docking. RESULTS: GC-MS analysis of SB detected a total of 20 compounds which were accepted by the Lipinski's rule. A total number of 16 compounds-related genes and T2DM-related genes (4,763) were identified, and 81 overlapping genes between them were selected. Gene set enrichment analysis exhibited that the mechanisms of SB against T2DM were associated with 12 signaling pathways, and the key mechanism might be to control blood glucose level by activating PPAR signaling pathway. Furthermore, the highest affinities were noted between four main compounds and six genes (FABP3-Propyleneglyco monoleate, FABP4-25-Oxo-27-norcholesterol, NR1H3-Campesterol, PPARA-ß-sitosterol, PPARD-ß-sitosterol, and PPARG-ß-sitosterol). CONCLUSION: Our study overall suggests that the four key compounds detected in SB might ameliorate T2DM severity by activating the PPAR signaling pathway.


Asunto(s)
Regulación de la Expresión Génica/efectos de los fármacos , Redes Reguladoras de Genes/efectos de los fármacos , Hipoglucemiantes/química , Fitoquímicos/química , Sorghum/química , Esteroles/química , Sitios de Unión , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Proteína 3 de Unión a Ácidos Grasos/antagonistas & inhibidores , Proteína 3 de Unión a Ácidos Grasos/genética , Proteína 3 de Unión a Ácidos Grasos/metabolismo , Proteínas de Unión a Ácidos Grasos/antagonistas & inhibidores , Proteínas de Unión a Ácidos Grasos/genética , Proteínas de Unión a Ácidos Grasos/metabolismo , Hipoglucemiantes/aislamiento & purificación , Hipoglucemiantes/farmacología , Receptores X del Hígado/antagonistas & inhibidores , Receptores X del Hígado/genética , Receptores X del Hígado/metabolismo , Simulación del Acoplamiento Molecular , PPAR alfa/antagonistas & inhibidores , PPAR alfa/genética , PPAR alfa/metabolismo , PPAR delta/antagonistas & inhibidores , PPAR delta/genética , PPAR delta/metabolismo , PPAR gamma/antagonistas & inhibidores , PPAR gamma/genética , PPAR gamma/metabolismo , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Extractos Vegetales/química , Unión Proteica , Conformación Proteica en Hélice alfa , Conformación Proteica en Lámina beta , Dominios y Motivos de Interacción de Proteínas , Transducción de Señal , Esteroles/aislamiento & purificación , Esteroles/farmacología , Relación Estructura-Actividad
8.
J Oleo Sci ; 69(11): 1389-1401, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33132278

RESUMEN

The oral route is the most prevalent route of drug administration among various routes. Dapagliflozin is an oral hypoglycemic drug used for lowering the blood glucose level. The objective of this work is to developed and optimized dapagliflozin loaded nanostructured lipid carriers (DG-NLCs) for the improvement of oral delivery. DG-NLCs were prepared by a high-pressure homogenization method (hot) and optimized by Box-Behnken design software using lipid, surfactant, and homogenization cycle as an independent variable. DG-NLCs were evaluated for particle size (Y1), entrapment efficiency (Y2), drug release (Y3). The DG-NLCs were further evaluated for morphology, thermal and X-ray diffraction analysis, ex-vivo intestinal permeation, and stability study. Particle size (nm), entrapment efficiency (%) and drug release (%) of all seventeen formulations were found in the range of 113.71-356.22 nm, 60.43-96.54% and 63.44-83.62% respectively. Morphology of optimized formulation exhibited spherical in shape confirmed by transmission electron microscopy. Thermal and X-ray diffraction analysis of NLCs showed the drug was solubilized and lost the crystallinity. DG-NLCs-opt exhibited dual release pattern initial fast and later sustained-release (90.01±2.01% in 24 h) whereas DG-dispersion showed 31.54±1.87% release in 24 h. Korsmeyer-Peppas model was found to be the best fit model (R2=0.999). The DG-NLCs-opt exhibited significant-high (p < 0.05, 1.293 µg/cm2/h) flux than DG-dispersion (0.2683 µg/cm2/h). Apparent permeation coefficient of DG-NLCs-opt was found to be significantly higher (p < 0.05, 4.14×10-5 cm/min) than DG-dispersion (8.61×10-6 cm/min). The formulation showed no significant changes (p < 0.05) on six months of storage study at 25±2°C/60±5%RH. The finding concluded that quality by design (QbD) based lipid nanocarrier for oral delivery could be a promising approach of dapagliflozin for the management of diabetes.


Asunto(s)
Compuestos de Bencidrilo , Portadores de Fármacos , Composición de Medicamentos , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Glucósidos , Hipoglucemiantes , Absorción Intestinal , Lípidos , Nanopartículas , Nanoestructuras , Administración Oral , Compuestos de Bencidrilo/química , Compuestos de Bencidrilo/metabolismo , Formas de Dosificación , Portadores de Fármacos/química , Diseño de Fármacos , Estabilidad de Medicamentos , Glucósidos/química , Glucósidos/metabolismo , Hipoglucemiantes/química , Hipoglucemiantes/metabolismo , Modelos Biológicos , Tamaño de la Partícula
9.
Biomolecules ; 10(11)2020 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-33147723

RESUMEN

Plants have been used as drugs to treat human disease for centuries. Ursonic acid (UNA) is a naturally occurring pentacyclic triterpenoid extracted from certain medicinal herbs such as Ziziphus jujuba. Since the pharmacological effects and associated mechanisms of UNA are not well-known, in this work, we attempt to introduce the therapeutic potential of UNA with a comparison to ursolic acid (ULA), a well-known secondary metabolite, for beneficial effects. UNA has a keto group at the C-3 position, which may provide a critical difference for the varied biological activities between UNA and ULA. Several studies previously showed that UNA exerts pharmaceutical effects similar to, or stronger than, ULA, with UNA significantly decreasing the survival and proliferation of various types of cancer cells. UNA has potential to exert inhibitory effects in parasitic protozoa that cause several tropical diseases. UNA also exerts other potential effects, including antihyperglycemic, anti-inflammatory, antiviral, and antioxidant activities. Of note, a recent study highlighted the suppressive potential of UNA against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Molecular modifications of UNA may enhance bioavailability, which is crucial for in vivo and clinical studies. In conclusion, UNA has promising potential to be developed in anticancer and antiprotozoan pharmaceuticals. In-depth investigations may increase the possibility of UNA being developed as a novel reagent for chemotherapy.


Asunto(s)
Antivirales/farmacología , Triterpenos/farmacología , Animales , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología , Antineoplásicos Fitogénicos/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Antiprotozoarios/química , Antiprotozoarios/farmacología , Antivirales/química , Betacoronavirus/efectos de los fármacos , Betacoronavirus/fisiología , Humanos , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Plantas/química , Triterpenos/química , Triterpenos/metabolismo
10.
J Food Sci ; 85(9): 2933-2942, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32794200

RESUMEN

Fuzhuan Brick-Tea is a postfermented product with the hypoglycemic effect, which is prepared from the leaves of Camellia sinensis var. sinensis. However, the material basis associated with the hypoglycemic effect was not clear. The present research was designed to explore the hypoglycemic effect of extract/fractions from Fuzhuan Brick-Tea in streptozotocin-induced type II diabetic mice. Then an ultra-high pressure liquid chromatography along with quadrupole time of flight mass spectrometry was used to analyze the phytochemicals in Fuzhuan Brick-Tea fractions. As a result, the hypoglycemic and hypolipidemic effects were evidently observed from the serum biochemical indexes and liver pathological examination in type II diabetic mice. In addition, there were total of 20 major components including eight lysophosphatidylcholines (Lyso-PCs), five fatty acids, and seven novel theophylline derivatives tentatively identified in the active fraction from water extract. Therefore, these components were assumed to contribute partly to the hypoglycemic effect of Fuzhuan Brick-Tea. These findings also give the evidence that the Lyso-PCs, fatty acids, and novel theophylline derivatives in Fuzhuan Brick-Tea may provide benefits in ameliorating disorders of glucose and lipid metabolism. PRACTICAL APPLICATION: This study suggests that the Lyso-PCs, fatty acids, and novel theophylline derivatives in Fuzhuan Brick-Tea may provide benefits in ameliorating disorders of glucose and lipid metabolism. It can be taken as a beneficial diet additive or nutraceutical.


Asunto(s)
Camellia sinensis/química , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Extractos Vegetales/administración & dosificación , Animales , Cromatografía Líquida de Alta Presión , Diabetes Mellitus Experimental/metabolismo , Ácidos Grasos/metabolismo , Fermentación , Humanos , Hipoglucemiantes/química , Metabolismo de los Lípidos , Hígado/metabolismo , Masculino , Ratones , Extractos Vegetales/química , Hojas de la Planta/química , Estreptozocina , Espectrometría de Masas en Tándem/métodos , Té/química
11.
Int J Vitam Nutr Res ; 90(5-6): 425-429, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32729784

RESUMEN

Objective: The objective of the present study is to investigate the effects of glutamine administration on postprandial glycemia, insulin, and C-peptide concentration in patients with type 2 diabetes. Methods: A randomized, double-blind, placebo-controlled trial was conducted on patients with type 2 diabetes so that 33 subjects were recruited in each group. The patients were randomly allocated to receive either 30 g/d glutamine or placebo (with instructions to take in half glass of ice-cold water 5 to 10 min before each main meal) for 6 weeks. Postprandial C-peptide, insulin, and glucose were measured at the baseline and at the end of the study at 30 and 90 min after consuming a meal comprising wheat-cake and reduced fat milk. Results: The repeated measures ANOVA revealed no significant difference between the groups for glucose and insulin after 6 weeks of intervention (p > 0.05). However, C-peptide was reduced in both intervention groups at all measurement points. Between-group differences remained significant by the end of the study (p = 0.02). Conclusions: Glutamine supplementation before each main meal does not represent an effective nutritional strategy to improve postprandial glycemic control or postprandial insulin secretion in type 2 diabetes patients.


Asunto(s)
Diabetes Mellitus Tipo 2 , Secreción de Insulina , Glucemia/metabolismo , Método Doble Ciego , Glutamina/metabolismo , Humanos , Hipoglucemiantes/química , Hipoglucemiantes/metabolismo , Insulina/química
12.
J Food Sci ; 85(7): 2177-2185, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32672871

RESUMEN

Phenolic profiles, antioxidant, antiproliferative, and hypoglycemic activities of the whole Ehretia macrophylla Wall. (EMW) fruit were investigated in the present study. Catechin (CE), o-methoxy benzoic acid (o-MBA), and rosmarinic acid (RA) were the predominant phenolics in free extract, while CE, vanillic acid (VA), and o-MBA were for bound extract. These extracts exhibited potential antioxidant capacity measured by peroxyl radical scavenging capacity (PSC), oxygen radical absorbance capacity (ORAC), and cellular antioxidant activity (CAA) assays. This fruit also possessed dose-dependently antiproliferative activity, and this may be due to the synergistic and additive effects of individual phenolics. Furthermore, EMW fruit showed favorable hypoglycemic activity via inhibition of activities of α-glucosidase and α-amylase, enhancement of glucose consumption, glycogen accumulation, and glycogen synthase 2 (GYS2) activity, and downregulation of activities of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK). Therefore, EMW fruit has the potential as an ingredient of functional foods to improve human health and shows promising applications with additional health and economical benefits. PRACTICAL APPLICATION: EMW fruit is a plant-based food rich in natural phenolic compounds, which suggesting its potential bioactivities for humans such as antioxidant, antiproliferative, and hypoglycemic activities. Our findings would provide a logical strategy to promote the comprehensive utilization of phenolics in EMW fruit with both health and economical benefits.


Asunto(s)
Antioxidantes/química , Boraginaceae/química , Hipoglucemiantes/química , Fenoles/química , Extractos Vegetales/química , Antioxidantes/farmacología , Línea Celular , Proliferación Celular/efectos de los fármacos , Frutas/química , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/farmacología , Humanos , Hipoglucemiantes/farmacología , Fenoles/farmacología , Extractos Vegetales/farmacología , alfa-Amilasas/antagonistas & inhibidores , alfa-Amilasas/química , alfa-Glucosidasas/química
13.
Food Chem ; 333: 127478, 2020 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-32663752

RESUMEN

Moringa oleifera Lam. (M. oleifera) leaves have long been consumed as both nutritive vegetable and popular folk medicine for hyperglycemia and hyperlipidemia in Kenya communities. In the current study, in vitro inhibition by M. oleifera leaf extract (MOLE, 90% (v/v) ethanol) of α-glucosidase and pancreatic lipase was demonstrated, followed by determination of the effects of MOLE on both glucose consumption and lipid levels (TC, TG, HDL-C and LDL-C) in 3T3-L1 cells. Potential ligands in MOLE were fast screened using affinity ultrafiltration LC-MS, and 14 and 10 components displayed certain binding affinity to α-glucosidase and pancreatic lipase, respectively. Docking studies revealed the binding energies and hydrogen bonds between potential ligands and enzymes. This study suggests that M. oleifera leaves may be a promising natural source for the prevention and treatment of hyperglycemia and hyperlipidemia as well as a functional food or other product for health care in the near future.


Asunto(s)
Moringa oleifera/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Células 3T3-L1 , Animales , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/farmacología , Humanos , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Hipolipemiantes/química , Hipolipemiantes/farmacología , Lipasa/antagonistas & inhibidores , Metabolismo de los Lípidos/efectos de los fármacos , Ratones
14.
Life Sci ; 256: 117910, 2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-32504753

RESUMEN

AIMS: Insulin (Ins) covalently modified by catecholestrogens (CEs) was commonly found in diabetic patients who have developed insulin resistance. Estrogenization of insulin altered its molecular function and effect carbohydrates metabolisms in these patients. Insulin resistance is a common phenomenon in diabetes but the exact mechanism remains unknown. In this study, binding specificity and affinity of autoantibodies against estrogenized insulin (4-hydroxyestradiol-insulin; 4-OHE2-Ins) were assayed in the serum of type 1 diabetes (T1D) patients in order to explain the phenomena behind insulin resistance. MATERIALS AND METHODS: Specificity and affinity of autoantibodies from the sera of 66 T1D patients and 41 controls were analyzed by direct binding, competition ELISA and quantitative precipitin titration. Insulin was also estimated in the serum of T1D patients by ELISA. KEY FINDING: Estrogenized insulin (4-OHE2-Ins) exhibited high affinity and specificity to T1D autoantibodies in comparison to Ins (p < .05) or 4-OHE2 (p < .001). Estrogenization of insulin alters its interaction with the insulin receptor (IR). The affinity constant of 4-OHE2-Ins with the T1D autoantibodies was found to be 1.41 × 10-7 M. SIGNIFICANCE: Estrogenization of insulin by catecholestrogen makes these molecules highly antigenic and produced high-affinity autoantibodies in T1D patients. As a result, patients develop insulin resistance and presented this molecule as a potential biomarker for T1D.


Asunto(s)
Autoanticuerpos/inmunología , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Estrógenos de Catecol/química , Hipoglucemiantes/química , Insulina/química , Adulto , Autoanticuerpos/metabolismo , Biomarcadores/metabolismo , Glucemia/análisis , Recolección de Muestras de Sangre , Propuestas de Licitación , Ensayo de Inmunoadsorción Enzimática , Estrógenos de Catecol/uso terapéutico , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Receptor de Insulina/inmunología , Receptor de Insulina/metabolismo , Sensibilidad y Especificidad
15.
Food Chem ; 328: 127076, 2020 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-32480257

RESUMEN

The tunillo (Stenocereus stellatus [Pfeiffer] Riccobono) is a relatively little known cactus fruit with a significant pharmacological potential. However, all currently known variants are identified visually mostly on the basis of pulp color. Differences in chemical composition and pharmacological properties also remain largely unknown. Support vector machine classifiers were applied to UV-Visible spectra of liquid samples to obtain the following, color-based categories of tunillo fruits: A1-white, A2-red, A3-purple, and A4-orange. The spectrum of A2-red could be duplicated by combining those from A3-purple and A4-orange, while UPGMA-based hierarchical clustering of psbA-trnH and matK suggested that certain differences in color might actually have a genetic basis. The pigment quantification established A2-red and A3-purple as the most suitable candidates for the extraction of betalains and complex colored matrices, respectively. A2-red also had the highest content of phenols and flavonoids and displayed a noticeable anti-hyperglycemic effect.


Asunto(s)
Cactaceae/química , Frutas/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Color , Sequías , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , México
16.
PLoS One ; 15(6): e0233963, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32530961

RESUMEN

Eclipta alba L., also known as false daisy, is well known and commercially attractive plant with excellent hepatotoxic and antidiabetic activities. Light is considered a key modulator in plant morphogenesis and survival by regulating important physiological cascades. Current study was carried out to investigate growth and developmental aspects of E. alba under differential effect of multispectral lights. In vitro derived callus culture of E. alba was exposed to multispectral monochromatic lights under controlled aseptic conditions. Maximum dry weight was recorded in culture grown under red light (11.2 g/L) whereas negative effect was observed under exposure of yellow light on callus growth (4.87 g/L). Furthermore, red light significantly enhanced phenolics and flavonoids content (TPC: 57.8 mg/g, TFC: 11.1 mg/g) in callus cultures compared to rest of lights. HPLC analysis further confirmed highest accumulation of four major compounds i.e. coumarin (1.26 mg/g), eclalbatin (5.00 mg/g), wedelolactone (32.54 mg/g) and demethylwedelolactone (23.67 mg/g) and two minor compounds (ß-amyrin: 0.38 mg/g, luteolin: 0.39 mg/g) in red light treated culture whereas stigmasterol was found optimum (0.22 mg/g) under blue light. In vitro based biological activities including antioxidant, antidiabetic and lipase inhibitory assays showed optimum values in cultures exposed to red light, suggesting crucial role of these phytochemicals in the enhancement of the therapeutic potential of E. alba. These results clearly revealed that the use of multispectral lights in in vitro cultures could be an effective strategy for enhanced production of phytochemicals.


Asunto(s)
Antioxidantes/metabolismo , Eclipta/metabolismo , Eclipta/efectos de la radiación , Hipoglucemiantes/metabolismo , Fitoquímicos/metabolismo , Antioxidantes/química , Cumarinas/metabolismo , Eclipta/crecimiento & desarrollo , Flavonoides/metabolismo , Hipoglucemiantes/química , Luz , Fenoles/metabolismo , Fitoquímicos/química , Metabolismo Secundario/efectos de la radiación , Técnicas de Cultivo de Tejidos
17.
PLoS One ; 15(6): e0235221, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32584888

RESUMEN

Ficus krishnae stem bark and leaves are used for diabetes treatment in traditional medicines. Stem bark of F. krishnae was sequentially extracted with hexane, methanol and water, and these extracts were tested for their antihyperglyceamic activity by oral glucose tolerance test (OGTT) in overnight fasted glucose loaded normal rats. Hexane extract showed significant glucose lowering activity in OGTT, and the triterpene alcohols (cycloartenol+24-methylenecycloartanol) (CA+24-MCA) were isolated together from it by activity guided isolation and characterized by NMR and mass spectroscopy. The ratio of the chemical constituents CA and 24-MCA in (CA+24-MCA) was determined as 2.27:1.00 by chemical derivatization and gas chromatographic quantification. (CA+24-MCA) in high fat diet-streptozotocin induced type II diabetic rats showed significant antidiabetes activity at 1 mg/kg and ameliorated derailed blood glucose and other serum biochemical parameters. Cytoprotective activity of (CA+24-MCA) from glucose toxicity was evaluated in cultured RIN-5F cells by MTT assay and fluorescent microscopy. (CA+24-MCA) in in vitro studies showed enhanced cell viability in RIN-5F cells and significant protection of beta cells from glucose toxicity. Both in in vivo and in vitro studies (CA+24-MCA) showed enhancement in insulin release from the beta cells. In short term toxicity studies in mice (CA+24-MCA) did not show any conspicuous toxic symptoms. The combination of the phytosterols (CA+24-MCA) obtained through activity guided isolation of the stem bark of F. krishnae showed significant activity, and therefore is a promising candidate for new generation antidiabetes drug development.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Ficus/química , Hipoglucemiantes/uso terapéutico , Fitosteroles/química , Triterpenos/química , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Diabetes Mellitus Experimental/inducido químicamente , Ficus/metabolismo , Prueba de Tolerancia a la Glucosa , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Insulina/metabolismo , Hígado/metabolismo , Masculino , Ratones , Conformación Molecular , Fitosteroles/aislamiento & purificación , Fitosteroles/uso terapéutico , Tallos de la Planta/química , Tallos de la Planta/metabolismo , Ratas , Ratas Wistar , Triterpenos/aislamiento & purificación , Triterpenos/uso terapéutico
18.
Life Sci ; 256: 117853, 2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-32470452

RESUMEN

AIMS: To investigate the diabetes-protective effect and weight-lowering potential of a novel long-acting triagonist at three metabolically related hormone receptors including glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon receptors. MAIN METHODS: Triagonist were designed in an iterative manner from native GLP-1, GIP and Glucogan. Main peptide chain (termed TG peptides) and subsequently modified LTG peptides were synthesized via solid phase synthesis. In vitro receptor activity assay was performed to screen the TG peptide with most balanced potency on all three receptors. The in vitro biological activities of modified TG peptides were further investigated by albumin-binding measurement and proteolytic cleavage test. Subsequently, oral glucose tolerance test (OGTT), pharmacokinetic test and chronic study were subjected to the acute and long-term efficacy evaluation of selected fusion peptide, LTG-6. KEY FINDINGS: TG-8 exhibited equally aligned constituent efficacy and supraphysiological potency on corresponding receptor without cross-reactivity. Modified TG-8, termed LTG-6, exerted the great binding affinity for human serum albumin and the enhanced rational controlled-release of TG-8 in vitro. Further OGTT in different gene knockout mice and diabetic mice demonstrated the promising hypoglycemic and insulinotropic abilities of LTG-6. After long-term treatment for 8 weeks, LTG-6 was proved superior to co-agonists to decrease the body weight and %HbA1c, improve reverse dyslipidemia and glycemic control in the DIO models. SIGNIFICANCE: LTG-6, as a newly designed long-acting triagonist, holds potential to correct the obesity related metabolic disorders.


Asunto(s)
Diabetes Mellitus Experimental/prevención & control , Receptor del Péptido 1 Similar al Glucagón/agonistas , Péptidos/farmacología , Receptores de la Hormona Gastrointestinal/agonistas , Receptores de Glucagón/agonistas , Animales , Peso Corporal/efectos de los fármacos , Prueba de Tolerancia a la Glucosa , Células HEK293 , Humanos , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Masculino , Enfermedades Metabólicas/etiología , Enfermedades Metabólicas/prevención & control , Ratones , Ratones Noqueados , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Péptidos/química , Ratas , Ratas Sprague-Dawley , Trombina/química
19.
J Nanobiotechnology ; 18(1): 67, 2020 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-32345323

RESUMEN

BACKGROUND: Exenatide is an insulinotropic peptide drug for type 2 diabetes treatment with low risk of hypoglycemia, and is administrated by subcutaneous injection. Oral administration is the most preferred route for lifelong treatment of diabetes, but oral delivery of peptide drug remains a significant challenge due to the absorption obstacles in gastrointestinal tract. We aimed to produce exenatide-loaded nanoparticles containing absorption enhancer, protectant and stabilizer using FDA approved inactive ingredients and easy to scale-up method, and to evaluate their long-term oral therapeutic effect in type 2 diabetes db/db mice. RESULTS: Two types of nanoparticles, named COM NPs and DIS NPs, were fabricated using anti-solvent precipitation method. In COM NPs, the exenatide was complexed with cholic acid and phosphatidylcholine to increase the exenatide loading efficiency. In both nanoparticles, zein acted as the cement and the other ingredients were embedded in zein nanoparticles by hydrophobic interaction. Casein acted as the stabilizer. The nanoparticles had excellent lyophilization, storage and re-dispersion stability. Hypromellose phthalate protected the loaded exenatide from degradation in simulated gastric fluid. Cholic acid promoted the intestinal absorption of the loaded exenatide via bile acid transporters. The exenatide loading efficiencies of COM NPs and DIS NPs were 79.7% and 53.6%, respectively. The exenatide oral pharmacological availability of COM NPs was 18.6% and DIS NPs was 13.1%. COM NPs controlled the blood glucose level of the db/db mice well and the HbA1c concentration significantly decreased to 6.8% during and after 7 weeks of once daily oral administration consecutively. Both DIS NPs and COM NPs oral groups substantially increased the insulin secretion by more than 60% and promoted the ß-cell proliferation by more than 120% after the 7-week administration. CONCLUSIONS: Both COM NPs and DIS NPs are promising systems for oral delivery of exenatide, and COM NPs are better in blood glucose level control than DIS NPs. Using prolamin to produce multifunctional nanoparticles for oral delivery of peptide drug by hydrophobic interaction is a simple and effective strategy.


Asunto(s)
Exenatida/farmacología , Hipoglucemiantes/farmacología , Células Secretoras de Insulina/efectos de los fármacos , Nanopartículas/química , Zeína/química , Administración Oral , Animales , Glucemia/análisis , Ácido Cólico/química , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/patología , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Exenatida/administración & dosificación , Exenatida/química , Tracto Gastrointestinal/química , Tracto Gastrointestinal/patología , Hemoglobina A Glucada/análisis , Semivida , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/química , Células Secretoras de Insulina/clasificación , Células Secretoras de Insulina/metabolismo , Mucosa Intestinal/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , Nanopartículas/metabolismo , Permeabilidad/efectos de los fármacos , Fosfatidilcolinas/química
20.
Life Sci ; 253: 117651, 2020 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-32304764

RESUMEN

AIMS: To investigate the combination of dimerization and PEGylation to enhance the receptor activation and in vivo stability of Oxyntomodulin (OXM). MAIN METHODS: All LDM peptides were produced by using standard method of solid phase synthesis. The in vitro effects of LDM peptides were assessed by glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GcgR) binding test and Proteolytic stability test. Subsequently, saline, Liraglutide and three doses of LDM-3 treated groups were subjected to the evaluation of aute and long-term efficacy. KEY FINDINGS: Five long-acting OXM conjugates, termed LDM-1 to LDM-5, were designed using cysteine (Cys)-specific modification reaction including the activated PEG, bisMal-NH2, and OXM-Cys, and all prepared with high purity. LDM-3 exhibited greater GLP-1R and GcgR activation and ameliorative serum stability. In addition, LDM-3 was identified with enhanced insulinotropic and glycemic abilities in the gene knockout mice. The prolonged glucose-lowering effects of the LDM-3 were proved by hypoglycemic duration test and multiple oral glucose tolerance tests (OGTTs) in the diet-induced obesity (DIO) mice. Furthermore, the pharmacokinetic tests in Sprague Dawley (SD) rat and cynomolgus monkey exhibited the lifespans of LDM-3 at 90 nmol·kg-1 were 101.5 h and 119.4 h, respectively. Nevertheless, consecutive 8-week administration of LDM-3 improved the cumulative body weight gain, food intake, % HbA1c, glucose tolerance and the pancreatic of the obese mice. SIGNIFICANCE: LDM-3, as a dual GLP-1R and GcgR agonist, holds potential to be developed as a promising therapeutic candidate for both diabetes and obesity.


Asunto(s)
Receptor del Péptido 1 Similar al Glucagón/metabolismo , Hipoglucemiantes/química , Oxintomodulina/química , Receptores de Glucagón/metabolismo , Animales , Glucemia/efectos de los fármacos , Diabetes Mellitus/metabolismo , Dimerización , Glucagón/metabolismo , Prueba de Tolerancia a la Glucosa , Hipoglucemiantes/farmacocinética , Macaca fascicularis , Masculino , Ratones , Ratones Noqueados , Ratones Obesos , Obesidad/metabolismo , Oxintomodulina/farmacocinética , Polietilenglicoles/química , Ratas Sprague-Dawley , Técnicas de Síntesis en Fase Sólida , Pérdida de Peso/efectos de los fármacos
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