RESUMEN
α-glucosidase, a pharmacological target for type 2 diabetes mellitus (T2DM), is present in the intestinal brush border membrane and catalyzes the hydrolysis of sugar linkages during carbohydrate digestion. Since α-glucosidase inhibitors (AGIs) modulate intestinal metabolism, they may influence oxidative stress and glycolysis inhibition, potentially addressing intestinal dysfunction associated with T2DM. Herein, we report on a study of an ortho-carbonyl substituted hydroquinone series, whose members differ only in the number and position of methyl groups on a common scaffold, on radical-scavenging activities (ORAC assay) and correlate them with some parameters obtained by density functional theory (DFT) analysis. These compounds' effect on enzymatic activity, their molecular modeling on α-glucosidase, and their impact on the mitochondrial respiration and glycolysis of the intestinal Caco-2 cell line were evaluated. Three groups of compounds, according their effects on the Caco-2 cells metabolism, were characterized: group A (compounds 2, 3, 5, 8, 9, and 10) reduces the glycolysis, group B (compounds 1 and 6) reduces the basal mitochondrial oxygen consumption rate (OCR) and increases the extracellular acidification rate (ECAR), suggesting that it induces a metabolic remodeling toward glycolysis, and group C (compounds 4 and 7) increases the glycolysis lacking effect on OCR. Compounds 5 and 10 were more potent as α-glucosidase inhibitors (AGIs) than acarbose, a well-known AGI with clinical use. Moreover, compound 5 was an OCR/ECAR inhibitor, and compound 10 was a dual agent, increasing the proton leak-driven OCR and inhibiting the maximal electron transport flux. Additionally, menadione-induced ROS production was prevented by compound 5 in Caco-2 cells. These results reveal that slight structural variations in a hydroquinone scaffold led to diverse antioxidant capability, α-glucosidase inhibition, and the regulation of mitochondrial bioenergetics in Caco-2 cells, which may be useful in the design of new drugs for T2DM and metabolic syndrome.
Asunto(s)
Antioxidantes , Metabolismo Energético , Inhibidores de Glicósido Hidrolasas , Hidroquinonas , alfa-Glucosidasas , Humanos , Células CACO-2 , alfa-Glucosidasas/metabolismo , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/metabolismo , Hidroquinonas/farmacología , Hidroquinonas/química , Metabolismo Energético/efectos de los fármacos , Glucólisis/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacosRESUMEN
Ayocote beans (Phaseolus coccineus L.) are a rich source of some bioactive molecules, such as phenolic compounds that exhibit antioxidant capacity that promote health benefits. Ayocote is mainly consumed after cooking, which can impact the antioxidant characteristics of the phenolic compounds responsible for some of its health benefits. Therefore, this study investigated the effects of boiling on the phenolic composition and bioactivities of ayocote beans before and after boiling. Boiling decreased the total phenolic content (70.2, 60.3, and 58.2%), total anthocyanin (74.3, 80.6, and 85.7%), and antioxidant activity (DPPH: 41.2, 46.9, and 59.1%; ORAC: 48.23, 53.6 and 65.7%) of brown, black, and purple ayocote beans, respectively. All the extracts also inhibited the activity of α-glucosidase with efficacy values from 29.7 to 87.6% and α-amylase from 25.31 to 56.2%, with moderate antiglycation potential (15.2 to 73.2%). Phenolic acids, anthocyanins, and flavonoid decreases were detected in boiled samples by HPLC-MS analysis. Although boiling reduced the phenolic compounds, bioactive compounds remained in a considerable content in boiled ayocote.
Asunto(s)
Antioxidantes , Phaseolus , Fenoles , Extractos Vegetales , Phaseolus/química , Fenoles/análisis , Fenoles/química , Antioxidantes/química , Antioxidantes/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , alfa-Amilasas/antagonistas & inhibidores , Antocianinas/análisis , Antocianinas/química , Antocianinas/farmacología , Flavonoides/análisis , Flavonoides/química , Culinaria , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Cromatografía Líquida de Alta PresiónRESUMEN
Protein hydrolysates with antioxidant potential have been reported to act as adjuvants in preventing and treating type-2 diabetes (T2D). This work investigated the biochemical, antidiabetic, antioxidant potential, and physicochemical properties of chia meal protein hydrolysate (CMPH). Bands smaller than 14 kDa were observed in the electrophoretic profile. The predominant amino acids were hydrophobic and aromatic. CMPH had the potential to inhibit α-amylase (IC50: 1.76 ± 0.13 mg/mL), α-glucosidase (IC50: 0.42 ± 0.13 mg/mL), and DPP-IV (IC50: 0.46 ± 0.14 mg/mL). Antioxidant activity for ABTS (IC50: 0.236 mg/mL), DPPH (8.83 ± 0.52%), and ORAC (IC25: 0.115 mg/mL). Against chia meal protein isolate (CMPI), CMPH has a broad solubility (pH 2-12.46). Particle size (624.5 ± 247.3 nm), low PDI (0.22 ± 0.06), ζ-potential (-31.1 ± 2.5 mV), and surface hydrophobicity (11,183.33 ± 2024.11) and the intrinsic fluorescence peak of CMPH was lower than that of CMPI. CMPH represents an alternative to add value to the agri-food co-product of the chia seed oil industry, generating food ingredients with outstanding antidiabetic and antioxidant potential.
Asunto(s)
Antioxidantes , Hipoglucemiantes , Hidrolisados de Proteína , Salvia hispanica , alfa-Amilasas , Hipoglucemiantes/química , Antioxidantes/química , Hidrolisados de Proteína/química , alfa-Amilasas/química , Salvia hispanica/química , alfa-Glucosidasas/química , alfa-Glucosidasas/metabolismo , Humanos , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/farmacología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Proteínas de Plantas/química , Interacciones Hidrofóbicas e Hidrofílicas , Salvia/químicaRESUMEN
Alpha-glucosidase inhibitors play an important role in Diabetes Mellitus (DM) treatment since they prevent postprandial hyperglycemia. The Glycoside Hydrolase family 13 (GH13) is the major family of enzymes acting on substrates containing α-glucoside linkages, such as maltose and amylose/amylopectin chains in starch. Previously, our group identified glycoconjugate 1H-1,2,3-triazoles (GCTs) inhibiting two GH13 α-glycosidases: yeast maltase (MAL12) and porcine pancreatic amylase (PPA). Here, we combined kinetic studies and computational methods on nine GCTs to characterize their inhibitory mechanism. They all behaved as reversible inhibitors, and kinetic models encompassed noncompetitive and various mechanisms of mixed-type inhibition for both enzymes. Most potent inhibitors displayed Ki values of 30 µM for MAL12 (GPESB16) and 37 µM for PPA (GPESB15). Molecular dynamics and docking simulations indicated that on MAL12, GPESB15 and GPESB16 bind in a cavity adjacent to the active site, while on the PPA, GPESB15 was predicted to bind at the entrance of the catalytic site. Notably, despite its putative location within the active site, the binding of GPESB15 does not obstruct the substrate's access to the cleavage site. Our study contributes to paving the way for developing novel therapeutic strategies for managing DM-2 through GH13 α-glycosidases inhibition.
Asunto(s)
Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Cinética , Ligandos , Porcinos , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Animales , Dominio Catalítico , alfa-Glucosidasas/metabolismo , alfa-Glucosidasas/química , Glicósido Hidrolasas/química , Glicósido Hidrolasas/metabolismo , Glicósido Hidrolasas/antagonistas & inhibidores , Bibliotecas de Moléculas Pequeñas/farmacología , Bibliotecas de Moléculas Pequeñas/química , Triazoles/química , Triazoles/farmacología , Modelos MolecularesRESUMEN
The research about α-methylene-γ-lactams is scarce; however, their synthesis has emerged in recent years mainly because they are isosters of α-methylene-γ-lactones. This last kind of compound is structurally most common in some natural products' nuclei, like sesquiterpene lactones that show biological activity such as anti-inflammatory, anticancer, antibacterial, etc., effects. In this work, seven α-methylene-γ-lactams were evaluated by their inflammation and α-glucosidase inhibition. Thus, compounds 3-methylene-4-phenylpyrrolidin-2-one (1), 3-methylene-4-(p-tolyl)pyrrolidin-2-one (2), 4-(4-chlorophenyl)-3-methylenepyrrolidin-2-one (3), 4-(2-chlorophenyl)-3-methylenepyrrolidin-2-one (4), 5-ethyl-3-methylene-4-phenylpyrrolidin-2-one (5), 5-ethyl-3-methylene-4-(p-tolyl)pyrrolidin-2-one (6) and 4-(4-chlorophenyl)-5-ethyl-3-methylenepyrrolidin-2-one (7) were evaluated via in vitro α-glucosidase assay at 1 mM concentration. From this analysis, 7 exerts the best inhibitory effect on α-glucosidase compared with the vehicle, but it shows a low potency compared with the reference drug at the same dose. On the other side, inflammation edema was induced using TPA (12-O-tetradecanoylphorbol 13-acetate) on mouse ears; compounds 1-7 were tested at 10 µg/ear dose. As a result, 1, 3, and 5 show a better inhibition than indomethacin, at the same doses. This is a preliminary report about the biological activity of these new α-methylene-γ-lactams.
Asunto(s)
Antiinflamatorios , Inhibidores de Glicósido Hidrolasas , Lactamas , alfa-Glucosidasas , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Lactamas/química , Lactamas/farmacología , Animales , alfa-Glucosidasas/metabolismo , Simulación del Acoplamiento Molecular , Ratones , Relación Estructura-Actividad , Simulación por Computador , Edema/tratamiento farmacológico , Edema/inducido químicamente , Estructura MolecularRESUMEN
Among antihyperglycemic drugs used for treating diabetes, α-glucosidase inhibitors generate the least adverse effects. This contribution aimed to evaluate the potential antidiabetic activity of Rumex crispus L. by testing its in vitro α-glucosidase inhibition and in vivo antihyperglycemic effects on rats with streptozotocin (STZ)-induced diabetes. Better inhibition of α-glucosidase was found with the methanol extract versus the n-hexane and dichloromethane extracts. The methanol extract of the flowers (RCFM) was more effective than that of the leaves (RCHM), with an IC50 of 7.3 ± 0.17 µg/mL for RCFM and 112.0 ± 1.23 µg/mL for RCHM. A bioactive fraction (F89s) also showed good α-glucosidase inhibition (IC50 = 3.8 ± 0.11 µg/mL). In a preliminary study, RCHM and RCFM at 150 mg/kg and F89s at 75 mg/kg after 30 days showed a significant effect on hyperglycemia, reducing glucose levels (82.2, 80.1, and 84.1%, respectively), and improved the lipid, renal, and hepatic profiles of the rats, comparable with the effects of metformin and acarbose. According to the results, the activity of R. crispus L. may be mediated by a diminished rate of disaccharide hydrolysis, associated with the inhibition of α-glucosidase. Thus, R. crispus L. holds promise for the development of auxiliary drugs to treat diabetes mellitus.
Asunto(s)
Diabetes Mellitus Experimental , Rumex , Ratas , Animales , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , alfa-Glucosidasas , Metanol , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/uso terapéutico , Hojas de la Planta , Diabetes Mellitus Experimental/tratamiento farmacológico , FloresRESUMEN
Current antidiabetic drugs have severe side effects, which may be minimized by new selective molecules that strongly inhibit α-glucosidase and weakly inhibit α-amylase. We have synthesized novel alkoxy-substituted xanthones and imidazole-substituted xanthones and have evaluated them for their in silico and in vitro α-glucosidase and α-amylase inhibition activity. Compounds 6c, 6e, and 9b promoted higher α-glucosidase inhibition (IC50 = 16.0, 12.8, and 4.0 µM, respectively) and lower α-amylase inhibition (IC50 = 76.7, 68.1, and >200 µM, respectively) compared to acarbose (IC50 = 306.7 µM for α-glucosidase and 20.0 µM for α-amylase). Contrarily, derivatives 10c and 10f showed higher α-amylase inhibition (IC50 = 5.4 and 8.7 µM, respectively) and lower α-glucosidase inhibition (IC50 = 232.7 and 145.2 µM, respectively). According to the structure-activity relationship, attaching 4-bromobutoxy or 4'-chlorophenylacetophenone moieties to the 2-hydroxy group of xanthone provides higher α-glucosidase inhibition and lower α-amylase inhibition. In silico studies suggest that these scaffolds are key in the activity and interaction of xanthone derivatives. Enzymatic kinetics studies showed that 6c, 9b, and 10c are mainly mixed inhibitors on α-glucosidase and α-amylase. In addition, drug prediction and ADMET studies support that compounds 6c, 9b, and 10c are candidates with antidiabetic potential.
Asunto(s)
Inhibidores de Glicósido Hidrolasas , Xantonas , Inhibidores de Glicósido Hidrolasas/farmacología , Simulación del Acoplamiento Molecular , alfa-Glucosidasas/metabolismo , alfa-Amilasas , Hipoglucemiantes/farmacología , Relación Estructura-Actividad , Imidazoles/farmacología , Xantonas/farmacología , Estructura MolecularRESUMEN
This study aimed to quantify verbascoside (VEB), perform molecular docking studies of VEB with the α-glucosidase (GL) of Bacillus stearothermophilus, and evaluate the inhibition of the enzyme by L. dulcis preparations. The substrate concentration and presence of reduced glutathione were evaluated for their effect on the inâ vitro inhibition of the GL enzyme. Assays were also performed in the presence and absence of simulated gastric fluid. The antidiabetic fractions 2 and 3 were the most inhibited GL, but their activity were significantly decreased in the presence of gastric fluid. Chromatographic analyses confirmed the predominant presence of VEB in the samples. The samples had VEB concentrations between 49.9 and 243.5â mg/g. Simulation of the molecular docking of VEB were consistent with its GL-inhibitory activity. It can conclude that the crude ethanol extract and fractions show inhibitory activity against the GL enzyme.
Asunto(s)
Lippia , Verbenaceae , Simulación del Acoplamiento Molecular , Inhibidores de Glicósido Hidrolasas/química , Glicósido Hidrolasas , Extractos Vegetales/química , Hialuronoglucosaminidasa , Hipoglucemiantes/química , alfa-Glucosidasas/químicaRESUMEN
Allium cepa L. is a commonly consumed vegetable that belongs to the Amaryllidaceae family and contains nutrients and antioxidants in ample amounts. In spite of the valuable food applications of onion bulb, its peel and outer fleshy layers are generally regarded as waste and exploration of their nutritional and therapeutic potential is still in progress with a very slow progression rate. The present study was designed with the purpose of doing a comparative analysis of the antioxidant potential of two parts of Allium cepa, i.g., bulb (edible part) and outer fleshy layers and dry peels (inedible part). Moreover, the inhibitory effect of the onion bulb and peel extracts on rat intestinal α-glucosidase and pancreatic α-amylase of porcine was also evaluated. The antioxidant potential of onion peel and bulb extracts were evaluated using 2,2-diphenyl- 1-picryl hydrazyl (DPPH), ferric-reducing antioxidant power assay (FRAP), 2,2-azino-bis- 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging assay, H2O2 radical scavenging activity and Fe2+ chelating activity. Total flavonoids and phenolic content of ethanolic extract of onion peel were significantly greater as compared to that of onion bulb. Ethanolic extract of onion peel also presented better antioxidant and free-radical scavenging activity as compared to the ethanolic extract of bulb, while the aqueous extract of bulb presented weakest antioxidative potential. Onion peel extract's α-glucosidase inhibition potential was also correlated with their phenolic and flavonoid contents. The current findings presented onion peel as a possible source of antioxidative agents and phenolic compounds that might be beneficial against development of various common chronic diseases that might have an association with oxidative stress. Besides, outer dry layers and fleshy peels of onion exhibited higher phenolic content and antioxidant activities, compared [...].(AU)
Allium cepa pertence à família Liliaceae e é rica em nutrientes e antioxidantes. Apesar das expressivas aplicações alimentares do bulbo da cebola, sua casca e outras camadas externas são geralmente consideradas resíduos, e seu potencial nutricional e terapêutico ainda é pouco explorado. O presente estudo foi delineado com o objetivo de investigar comparativamente o potencial antioxidante de duas partes de Allium cepa, por exemplo o bulbo (parte comestível) e camadas externas e cascas secas (parte não comestível). Além disso, o efeito inibitório dos extratos do bulbo de cebola e casca sobre a α-glucosidase intestinal de ratos e α-amilase pancreática suína também foi avaliado. O potencial antioxidante dos extratos da casca de cebola e bulbo foi avaliado utilizando-se 2,2-difenil-1-picrilhidrazil (DPPH), método de poder antioxidante de redução do ferro (FRAP), método 2,2-azino-bis-3-etilbenzotiazolina-6-ácido sulfônico (ABTS) de eliminação de radicais, atividade de eliminação de radicais H2O2 e atividade quelante do Fe2+. Os flavonoides totais e os teores fenólicos do extrato de etanol da casca de cebola foram significativamente maiores quando comparados ao do bulbo. O extrato de etanol da casca de cebola também apresentou melhor atividade antioxidante e eliminação de radicais livres quando comparado ao extrato de etanol do bulbo, enquanto o extrato aquoso de bulbo apresentou menor potencial antioxidante. O potencial de inibição da α-glicosidase dos extratos de casca de cebola correlacionou-se com seus teores fenólicos e de flavonoides. Os resultados encontrados identificaram que a casca de cebola é uma possível fonte de agentes antioxidantes e compostos fenólicos que podem ser benéficos contra o desenvolvimento de várias doenças crônicas que estão associadas ao estresse oxidativo. Além disso, as camadas externas secas e as cascas da cebola exibiram maior conteúdo fenólico e atividades [...].(AU
Asunto(s)
Cebollas , Antioxidantes/análisis , Estrés Oxidativo/efectos de los fármacos , Inhibidores de Glicósido Hidrolasas/análisisRESUMEN
Allium cepa L. is a commonly consumed vegetable that belongs to the Amaryllidaceae family and contains nutrients and antioxidants in ample amounts. In spite of the valuable food applications of onion bulb, its peel and outer fleshy layers are generally regarded as waste and exploration of their nutritional and therapeutic potential is still in progress with a very slow progression rate. The present study was designed with the purpose of doing a comparative analysis of the antioxidant potential of two parts of Allium cepa, i.g., bulb (edible part) and outer fleshy layers and dry peels (inedible part). Moreover, the inhibitory effect of the onion bulb and peel extracts on rat intestinal α-glucosidase and pancreatic α-amylase of porcine was also evaluated. The antioxidant potential of onion peel and bulb extracts were evaluated using 2,2-diphenyl- 1-picryl hydrazyl (DPPH), ferric-reducing antioxidant power assay (FRAP), 2,2-azino-bis- 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging assay, H2O2 radical scavenging activity and Fe2+ chelating activity. Total flavonoids and phenolic content of ethanolic extract of onion peel were significantly greater as compared to that of onion bulb. Ethanolic extract of onion peel also presented better antioxidant and free-radical scavenging activity as compared to the ethanolic extract of bulb, while the aqueous extract of bulb presented weakest antioxidative potential. Onion peel extract's α-glucosidase inhibition potential was also correlated with their phenolic and flavonoid contents. The current findings presented onion peel as a possible source of antioxidative agents and phenolic compounds that might be beneficial against development of various common chronic diseases that might have an association with oxidative stress. Besides, outer dry layers and fleshy peels of onion exhibited higher phenolic content and antioxidant activities, compared [...].
Allium cepa pertence à família Liliaceae e é rica em nutrientes e antioxidantes. Apesar das expressivas aplicações alimentares do bulbo da cebola, sua casca e outras camadas externas são geralmente consideradas resíduos, e seu potencial nutricional e terapêutico ainda é pouco explorado. O presente estudo foi delineado com o objetivo de investigar comparativamente o potencial antioxidante de duas partes de Allium cepa, por exemplo o bulbo (parte comestível) e camadas externas e cascas secas (parte não comestível). Além disso, o efeito inibitório dos extratos do bulbo de cebola e casca sobre a α-glucosidase intestinal de ratos e α-amilase pancreática suína também foi avaliado. O potencial antioxidante dos extratos da casca de cebola e bulbo foi avaliado utilizando-se 2,2-difenil-1-picrilhidrazil (DPPH), método de poder antioxidante de redução do ferro (FRAP), método 2,2-azino-bis-3-etilbenzotiazolina-6-ácido sulfônico (ABTS) de eliminação de radicais, atividade de eliminação de radicais H2O2 e atividade quelante do Fe2+. Os flavonoides totais e os teores fenólicos do extrato de etanol da casca de cebola foram significativamente maiores quando comparados ao do bulbo. O extrato de etanol da casca de cebola também apresentou melhor atividade antioxidante e eliminação de radicais livres quando comparado ao extrato de etanol do bulbo, enquanto o extrato aquoso de bulbo apresentou menor potencial antioxidante. O potencial de inibição da α-glicosidase dos extratos de casca de cebola correlacionou-se com seus teores fenólicos e de flavonoides. Os resultados encontrados identificaram que a casca de cebola é uma possível fonte de agentes antioxidantes e compostos fenólicos que podem ser benéficos contra o desenvolvimento de várias doenças crônicas que estão associadas ao estresse oxidativo. Além disso, as camadas externas secas e as cascas da cebola exibiram maior conteúdo fenólico e atividades [...].
Asunto(s)
Antioxidantes/análisis , Cebollas , Estrés Oxidativo/efectos de los fármacos , Inhibidores de Glicósido Hidrolasas/análisisRESUMEN
Leaf and fruit decoctions of Schinus areira L. from northwest Argentina were investigated here. Phenolic compounds and organic acids were analyzed by HPLC. Antioxidant capacity and α-glucosidase inhibition were determined by using in vitro tests. The general toxicity was assessed against Artemia salina nauplii. Hyperoside and 3 O-caffeoylquinic acid in leaf decoctions; gallic acid and catechin in fruit decoction were the major phenolic compounds. Malic and citric acids were the main organic acid quantified in the leaf and fruit decoctions, respectively. Fruit decoction had a relatively important content of shikimic acid, precursor of Tamiflu. Leaf decoction presents a greater richness in bioactive compounds with antiradical activity against DPPHâ, O2â-and âNO radicals. S. areira leaves and fruits had α-glucosidase inhibitory activity comparable to hyperoside and acarbose. Fruit decoction was not eco-toxic; leaf decoction showed significant eco-toxic activity and could be chosen for the search of other bioactive compounds with pharmacological activity.
Se investigaron decocciones de hojas y frutos de Schinus areira L. del noroeste de Argentina. Compuestos fenólicos y ácidos orgánicos se analizaron mediante HPLC. Capacidad antioxidante e inhibición de α-glucosidasa se determinaron in vitro. Se evaluó toxicidad general con Artemia salina. Los principales compuestos fenólicos fueron hiperósido y ácido 3 O-cafeoilquínico en hojas y ácido gálico y catequina en frutos. Los principales ácidos orgánicos cuantificados fueron málico en hojas y cítrico en frutos. Ácido shikímico, precursor del Tamiflu está presente en decocción de frutos con un contenido relativamente importante. La de hojas presenta una mayor riqueza en compuestos bioactivos con actividad antirradicalaria frente a DPPHâ, O2â-y âNO. Las hojas y frutos de S. areira tenían una actividad inhibidora de la α-glucosidasa comparable a la de hiperósido y acarbosa. La decocción de frutas no fue eco-tóxica, pero sí la de hojas que podría ser fuente de compuestos bioactivos con actividad farmacológica.
Asunto(s)
Extractos Vegetales/química , Anacardiaceae/química , Antioxidantes/química , Extractos Vegetales/toxicidad , Cromatografía Líquida de Alta Presión/métodos , Hojas de la Planta/química , Ácidos Orgánicos/análisis , Compuestos Fenólicos , Inhibidores de Glicósido Hidrolasas , Frutas/químicaRESUMEN
The MeOH:H2O (7:3) extracts of leaves from Chilean bean landraces were assessed for total phenolic (TP), total flavonoid (TF), total proanthocyanidin (TPA) content, antioxidant capacity (ORAC, FRAP, TEAC, CUPRAC, DPPH) and the inhibition of enzymes associated with metabolic syndrome (α-glucosidase, α-amylase, pancreatic lipase). The chemical profiles were analyzed by HPLC-DAD. Higher antioxidant activity in the ORAC and CUPRAC assay was found for the landrace Coscorrón, and the best effect in the TEAC for Sapito, respectively. The main phenolics were flavonol glycosides and caffeic acid derivatives. The extracts presented strong activity against α-glucosidase, but were inactive towards α-amylase and pancreatic lipase. The leaf extract from the Sapito landrace was fractionated to isolate the main α-glucosidase inhibitors, leading to caffeoylmalic acid with an IC50 of 0.21 µg/mL. The HPLC fingerprints of the leaves differentiate three groups of chemical profiles, according to the main phenolic content. A significant correlation was found between the α-glucosidase inhibition, the content of caffeoylmalic acid (r = -0.979) and kaempferol 3-O-ß-D-glucoside (r = 0.942) in the extracts. The presence of α-glucosidase inhibitors in the leaves of Chilean beans support their potential as a source of bioactive compounds.
Asunto(s)
Fabaceae , alfa-Glucosidasas , Antioxidantes/química , Antioxidantes/farmacología , Chile , Fabaceae/química , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/farmacología , Lipasa , Fenoles/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , alfa-Amilasas , alfa-Glucosidasas/metabolismoRESUMEN
Aiming at finding natural sources of antidiabetics agents, 15 extracts from Brazilian medicinal plants of the Atlantic Forest and Amazon region were tested against α-glucosidase enzyme. Plants were selected based on the taxonomic relationships with genera including several species with antidiabetic activity. In this screening, the extracts obtained from the flowers of Hyptis monticola and the leaves of Lantana trifolia and Lippia origanoides resulted endowed with promising anti-α-glucosidase activity. The extracts from H. monticola and from L. origanoides collected in two different areas, were characterised by ultra-high performance liquid chromatography coupled to mass spectrometry. Bioassay-guided fractionation led to the identification of several enzyme inhibiting compounds, among them the mechanism of action of naringenin and pinocembrin was investigated. The two L. origanoides extracts showed differences in bioactivity and in the phytochemical profiles. The fractionation of the extract from H. monticola led to a partial loss of the inhibitory effect.
Asunto(s)
Inhibidores de Glicósido Hidrolasas/farmacología , Hyptis/química , Lantana/química , Extractos Vegetales/farmacología , Plantas Medicinales/química , alfa-Glucosidasas/metabolismo , Brasil , Cromatografía Líquida de Alta Presión , Relación Dosis-Respuesta a Droga , Flores/química , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Espectrometría de Masas , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Saccharomyces cerevisiae/enzimología , Relación Estructura-ActividadRESUMEN
Phytochemical investigation of the stems of B. pulchella led to the isolation of the known compounds identified as a mixture of taraxerone (1) and ß-amirenone (2), a mixture of sitosterol (3) and stigmasterol (4), 2-hydroxy-3,5-dimethoxybibenzyl (5), 3',4'-dihydroxyphenyl-chroman-7-ol (6), fisetinidol (7), epicatechin (8), guibourtinidol (9), vanillic acid (10), 6'-O-vanilloylisotachioside (11) and 6'-O-syringoylisotachioside (12). The structures of these compounds were elucidated on the basis of their NMR spectroscopic data. The antioxidant activity of compound 7 has been investigated using DPPH° and ABTS°+ assays and the results showed inhibition in the both models. The compounds 6, 7 and 9 showed strong alpha-glucosidase inhibitory activities, being more active than acarbose, the positive control. In addition, all the compounds were isolated from B. pulchella for the first time, and among them, compounds 11 and 12 have not been reported previously from this genus.
Asunto(s)
Antioxidantes , Bauhinia , Inhibidores de Glicósido Hidrolasas , Antioxidantes/química , Antioxidantes/farmacología , Bauhinia/química , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/farmacología , Fitoquímicos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , alfa-GlucosidasasRESUMEN
Echeveria subrigida is native to Mexico and its methanol extract (ME) shows relevant biological activities for human health, including the α-glucosidase inhibitory (αGI) activity that suggests its antidiabetic potential. Fractionation of the ME based on the αGI activity (IC50 in µg/mL) showed that quercetin-3-O-ß-glucoside (131.1), isorhamnetin-3-O-ß-glucoside (166.4), and dimers to heptamers proanthocyanidins (9.6) were among the main responsible of αGI activity in the ME. The purified compounds showed better activity than acarbose (IC50 = 4426 µg/mL).
Asunto(s)
Proantocianidinas , alfa-Glucosidasas , Inhibidores de Glicósido Hidrolasas/farmacología , Humanos , Hipoglucemiantes/farmacología , Extractos Vegetales/farmacología , Hojas de la PlantaRESUMEN
iabetes mellitus is one of the most common non-contagious diseases. In 2017, The International Diabetes Federation reported that around 425 million people suffer from diabetes worldwide. Medications used for the treatment of diabetes lead to unwanted side effects, and thus, new safe drugs are necessary. Some natural plant-based products exhibit anti hyperglycemic activity and low toxicity. The aim of this study was to evaluate the antihyperglycemic activity (using both in vitro and in vivo models) as well as cytotoxicity of the extracts obtained from various plants. Nine extracts from a total of eight plant species were subjected to in vitro α-amylase and α-glucosidase inhibition assays. Subsequently, they were assessed through the ex vivo everted sac assay, and finally, the in vivo antihyperglycemic activity was evaluated. The extracts obtained from Ceanothus coeruleus, Chrysactinia mexicana and Zanthoxylum fagara inhibited the activities of α-amylase and α-glucosidase in the in vitro assays. Ethyl acetate and hydroalcoholic extracts from Jatropha dioica, hydroalcoholic extract from Salvia ballotaeflora and Chrysactinia mexicana, as well as methanolic extract from Ricinus communis and Zanthoxylum fagara significantly reduced the glucose uptake in the ex vivo everted intestinal sac test. All the eight extracts showed antihyperglycemic effect through the in vivo model of the Glucose Tolerance Test, using starch as the carbohydrate source. The antihyperglycemic effect of the extracts could be mediated through the inhibition of digestive enzymes and/or the absorption of glucose through the intestine. However, the mechanism of action for the hydroalcoholic extract of Salvia texana and the methanolic extract of Turnera diffusa, which showed a strong in vivo antihyperglycemic effect, is unclear.
Asunto(s)
Diabetes Mellitus/prevención & control , Hipoglucemiantes/farmacología , Extractos Vegetales/farmacología , Plantas Medicinales/química , Animales , Glucemia/metabolismo , Supervivencia Celular/efectos de los fármacos , Chlorocebus aethiops , Diabetes Mellitus/sangre , Diabetes Mellitus/metabolismo , Evaluación Preclínica de Medicamentos , Glucosa/metabolismo , Glucosa/farmacocinética , Prueba de Tolerancia a la Glucosa/métodos , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/farmacología , Humanos , Hipoglucemiantes/química , Absorción Intestinal/efectos de los fármacos , Masculino , Metanol/química , México , Fitoterapia/métodos , Extractos Vegetales/química , Plantas Medicinales/clasificación , Ratas Wistar , Células VeroRESUMEN
Several species of the Myrcia genus have been used in folk medicine to treat diabetes. Therefore, the aim of this work was to investigate the inhibitory activity of α-glucosidase and pancreatic lipase in the crude extract (EBF) and in the ethyl acetate fraction (FFA) of Myrcia hatschbachii, as well as to identify isolated phenolic compounds and to evaluate the antioxidant property and preliminary in vitro toxicity against Artemia salina. EBF (IC50: 3.21 µg/mL) and FFA (IC50: 1.14 µg/mL) showed inhibitory activity superior to acarbose (IC50: 193.65 µg/mL). In addition, they showed inhibitory effects of pancreatic lipase (IC50: 556.58 µg/mL for EBF and 532.68 µg/mL for FFA), antioxidant potential, absence of preliminary toxicity and presence of gallic andellagic acids in FFA. The relevant results in the inhibition of α-glucosidase and pancreatic lipase motivate new studies for the development of herbal medicines that assist in the treatment of diabetic patients.
Varias especies del género Myrcia se han utilizado en la medicina popular para tratar la diabetes. Por lo tanto, el objetivo de este trabajo fue investigar la actividad inhibitoria de la α-glucosidasa y la lipasa pancreática en el extracto crudo (EBF) y en la fracción de acetato de etilo (FFA) de Myrcia hatschbachii, así como identificar compuestos fenólicos aislados y evaluar la propiedad antioxidante y toxicidad in vitro preliminar contra Artemia salina. EBF (IC50: 3.21 µg/mL) y FFA (IC50: 1.14 µg/mL) mostraron una actividad inhibitoria superior a la acarbosa (IC50: 193.65 µg/mL). Además, mostraron efectos inhibitorios de la lipasa pancreática (IC50: 556.58 µg/mL para EBF y 532.68 µg/mL para FFA), potencial antioxidante, ausencia de toxicidad preliminar y presencia de ácidos gálico y elágico en FFA. Los resultados relevantes en la inhibición de la α-glucosidasa y la lipasa pancreática motivan nuevos estudios para el desarrollo de medicamentos a base de hierbas que ayudan en el tratamiento de pacientes diabéticos.
Asunto(s)
Extractos Vegetales/farmacología , Myrtaceae/química , Inhibidores de Glicósido Hidrolasas/farmacología , Lipasa/efectos de los fármacos , Antioxidantes/farmacología , Páncreas/enzimología , Fenoles/análisis , Difracción de Rayos X , Técnicas In Vitro , Extractos Vegetales/toxicidad , Extractos Vegetales/química , Depuradores de Radicales Libres , Mezclas Complejas , Ácido Elágico , Ácido Gálico , Antioxidantes/químicaRESUMEN
Fractionation of an aqueous extract from the aerial parts of Ageratina grandifolia yielded a new natural product, namely, 4-hydroxy-3-((S)-1'-angeloyloxy-(R)-2',3'-epoxy-3'-methyl)butylacetophenone (1), along with eight known compounds, including three flavonoids (2-4) and five chromenes (5-9). NMR data interpretation and DFT-calculated chemical shifts combined with DP4+ statistical and J-DP4 probability analyses allowed for the complete characterization of compound 1. The presence of compound 1 in a plant that biosynthesizes 2,2-dimethylchromenes is noteworthy, because an epoxy derivative has long been postulated as the reaction intermediate from the prenylated p-hydroxyacetophenones to cyclic dimethylchromenes. So far, this key intermediate has not been isolated, due to its purported chemical instability. Thus, this is the first report of a potential epoxide intermediate, leading to any of the chromene constituents of this plant. Compounds 1-9 inhibited yeast α-glucosidase with IC50 values ranging from 0.79 to 460 µM (acarbose, IC50 = 278.7 µM). The most active compounds were quercetagetin-7-O-(6-O-caffeoyl-ß-d-glucopyranoside (3) and 6-hydroxykaempferol-7-O-(6-O-caffeoyl-ß-d-glucopyranoside (4). Kinetic analysis of 3 revealed its mixed-type inhibitor nature. Docking studies into the crystallographic structure of yeast α-glucosidase (pdb 3A4A) predicted that 3 and 4 bind at the catalytic site of the enzyme.
Asunto(s)
Ageratina/química , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , México , Simulación del Acoplamiento Molecular , Estructura Molecular , Aceites Volátiles/química , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Componentes Aéreos de las Plantas/química , Extractos Vegetales/química , Saccharomyces cerevisiae/enzimologíaRESUMEN
The survival kinetics of Listeria monocytogenes (9 log CFU/mL) as a post-fermentation contaminant in probiotic fermented milk (Lactobacillus acidophilus La-5, 8-9 log CFU/mL) processed with milk subjected to ohmic heating (0, 4, 6, and 8 V/cm; CONV, OH4, OH6, OH8, 90-95 °C/5 min) was investigated using Weibull predictive model. Additionally, the presence of bioactive compounds (antioxidant activity, inhibition of the enzymes α-glucosidase, α-amylase, and angiotensin-converting) and sensory analysis (consumer test) of probiotic fermented milks were evaluated. Overall, OH provided a decrease in the viability of Listeria monocytogenes, suitable Lactobacillus acidophilus counts, and satisfactory results in the gastrointestinal tract survival. The Weibull model presented an excellent fit to the data of all conditions. Furthermore, lower δ values (217-298 against 665 h, CONV), and increased R2 values (0.99 against 0.98, CONV) were obtained for the OH-treated samples, emphasizing the best performance of OH data. In addition, OH improved the generation of bioactive compounds as well as the sensory acceptance. Indeed, considering functional and safety purposes, OH presented as an interesting technology to be used in milk for manufacturing probiotic fermented milk.