RESUMEN

In the age of information technology and the additional computational search tools and software available, this systematic review aimed to identify potential therapeutic targets for obesity, evaluated in silico and subsequently validated in vivo. The systematic review was initially guided by the research question "What therapeutic targets have been used in in silico analysis for the treatment of obesity?" and structured based on the acronym PECo (P, problem; E, exposure; Co, context). The systematic review protocol was formulated and registered in PROSPERO (CRD42022353808) in accordance with the Preferred Reporting Items Checklist for Systematic Review and Meta-Analysis Protocols (PRISMA-P), and the PRISMA was followed for the systematic review. The studies were selected according to the eligibility criteria, aligned with PECo, in the following databases: PubMed, ScienceDirect, Scopus, Web of Science, BVS, and EMBASE. The search strategy yielded 1142 articles, from which, based on the evaluation criteria, 12 were included in the systematic review. Only seven these articles allowed the identification of both in silico and in vivo reassessed therapeutic targets. Among these targets, five were exclusively experimental, one was exclusively theoretical, and one of the targets presented an experimental portion and a portion obtained by modeling. The predominant methodology used was molecular docking and the most studied target was Human Pancreatic Lipase (HPL) (n = 4). The lack of methodological details resulted in more than 50% of the papers being categorized with an "unclear risk of bias" across eight out of the eleven evaluated criteria. From the current systematic review, it seems evident that integrating in silico methodologies into studies of potential drug targets for the exploration of new therapeutic agents provides an important tool, given the ongoing challenges in controlling obesity.

Asunto(s)

Simulación por Computador , Obesidad , Humanos , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Animales , Simulación del Acoplamiento Molecular , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/uso terapéutico , Lipasa/metabolismo , Lipasa/antagonistas & inhibidores , Terapia Molecular Dirigida/métodos

RESUMEN

α,ß-amyrenone (ABAME) is a triterpene derivative with many biological activities; however, its potential pharmacological use is hindered by its low solubility in water. In this context, the present work aimed to develop inclusion complexes (ICs) of ABAME with γ- and ß-cyclodextrins (CD), which were systematically characterized through molecular modeling studies as well as FTIR, XRD, DSC, TGA, and SEM analyses. In vitro analyses of lipase activity were performed to evaluate possible anti-obesity properties. Molecular modeling studies indicated that the CD:ABAME ICs prepared at a 2:1 molar ratio would be more stable to the complexation process than those prepared at a 1:1 molar ratio. The physicochemical characterization showed strong evidence that corroborates with the in silico results, and the formation of ICs with CD was capable of inducing changes in ABAME physicochemical properties. ICs was shown to be a stronger inhibitor of lipase activity than Orlistat and to potentiate the inhibitory effects of ABAME on porcine pancreatic enzymes. In conclusion, a new pharmaceutical preparation with potentially improved physicochemical characteristics and inhibitory activity toward lipases was developed in this study, which could prove to be a promising ingredient for future formulations.

Asunto(s)

Inhibidores Enzimáticos/farmacología , Lipasa/antagonistas & inhibidores , Triterpenos/farmacología , beta-Ciclodextrinas/farmacología , Animales , Rastreo Diferencial de Calorimetría , Simulación por Computador , Inhibidores Enzimáticos/química , Lipasa/química , Orlistat/farmacología , Solubilidad/efectos de los fármacos , Espectroscopía Infrarroja por Transformada de Fourier , Porcinos , Triterpenos/síntesis química , Triterpenos/química , Difracción de Rayos X , beta-Ciclodextrinas/química

RESUMEN

The purpose of this study was to perform a parallel and comparative investigation of the effects of a Myrciaria jaboticaba (common name jabuticaba) peel extract and of its constituent cyanidin-3-O-glucoside on the overall process of starch and triglyceride intestinal absorption. The peel extract inhibited both the porcine pancreactic α-amylase and the pancreatic lipase but was 13.6 times more potent on the latter (IC50 values of 1963 and 143.9 µg mL-1, respectively). Cyanidin-3-O-glucoside did not contribute significantly to these inhibitions. The jabuticaba peel extract inhibited starch absorption in mice at doses that were compatible with its inhibitory action on the α-amylase. No inhibition of starch absorption was found with cyanidin-3-O-glucoside doses compatible with its content in the extract. The extract also inhibited triglyceride absorption, but at doses that were considerably smaller than those predicted by its strength in inhibiting the pancreatic lipase (ID50 = 3.65 mg kg-1). In this case, cyanidin-3-O-glucoside was also strongly inhibitory, with 72% inhibition at the dose of 2 mg kg-1. When oleate + glycerol were given to mice, both the peel extract and cyanidin-3-O-glucoside strongly inhibited the appearance of triglycerides in the plasma. The main mechanism seems, thus, not to be the lipase inhibition but rather the inhibition of one or more steps (e.g., transport) in the events that lead to the transformation of free fatty acids in the intestinal tract into triglycerides. Due to the low active doses, the jabuticaba peel extract presents many favourable perspectives as an inhibitor of fat absorption and cyanidin-3-O-glucoside seems to play a decisive role.

Asunto(s)

Antocianinas/farmacología , Myrtaceae/química , Extractos Vegetales/farmacología , Almidón/metabolismo , Triglicéridos/metabolismo , Animales , Antocianinas/química , Frutas/química , Inhibidores de Glicósido Hidrolasas , Lipasa/antagonistas & inhibidores , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Ratones , Extractos Vegetales/química , Almidón/química , Porcinos , Triglicéridos/sangre , Triglicéridos/química

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: species of Terminalia (Combretaceae) are used to treat diabetes and metabolic disorders in Asia, Africa, and America. Terminalia phaeocarpa Eichler is an endemic tree from Brazil, popularly known as capitão. This species is closely related to Terminalia argentea Mart., also vulgarly known as capitão, a native but not endemic tree. Due to their phenotype similarity, these species might eventually prove inseparable and they are indistinctly used by locals to treat diabetes, among other diseases. The potential antidiabetic effect of T. argentea has been previously reported, whereas the biological effects and chemical composition of T. phaeocarpa have never been addressed so far. AIM OF THE STUDY: investigate the hypoglycaemic effect of an ethanol extract (EE) of T. phaeocarpa leaves and its ethyl acetate (FrEtOAc) and hydromethanolic (FrMEOH) fractions, in addition to their activity on the release of pro-inflammatory mediators and inhibition of lipase, α-amylase, and α-glucosidase enzymes. Additionally, it aimed to characterize the chemical composition of the extract and fractions, seeking to identify the compounds related to the biological activities. MATERIALS AND METHODS: The effect on the release of TNF-α, IL-1ß, and CCL-2 was evaluated in LPS-stimulated THP-1 cells (ATCC TIB-202). The inhibition of lipase, α-amylase, and α-glucosidase was tested in vitro, whereas the hypoglycemic effect was assayed in the oral starch tolerance test. The chemical composition was investigated by extensive UHPLC-DAD-ESI-MS/MS analyses. RESULTS: The extract and derived fractions reduced TNF-α (EE pIC50 = 4.58 ± 0.01; FrEtOAc pIC50 = 4.69 ± 0.01; FrMeOH pIC50 = 4.54 ± 0.02) and IL-1ß (EE pIC50 = 4.86 ± 0.02; FrEtOAc pIC50 = 4.86 ± 0.02; FrMeOH pIC50 = 4.75 ± 0.01) release by LPS-stimulated THP-1 cells in a concentration-dependent manner, whereas the inhibitory effect on CCL-2 release did not reach a clear linear relationship for the tested concentrations. The extract and fractions also inhibited in vitro the activity of lipase (EE pIC50 = 3.97 ± 0.12; FrEtOAc pIC50 = 3.87 ± 0.04; FrMeOH pIC50 = 3.67 ± 0.14), α-amylase (EE pIC50 = 4.46 ± 0.27; FrEtOAc pIC50 = 5.47 ± 0.27; FrMeOH pIC50 = 4.26 ± 0.22), and α-glucosidase (EE pIC50 = 5.46 ± 0.05; FrEtOAc pIC50 = 5.79 ± 0.11; FrMeOH pIC50 = 5.74 ± 0.05). The pIC50 values of the test samples were lower than those obtained with orlistat (7.59 ± 0.08) and acarbose (6.04 ± 0.37 and 7.63 ± 0.04) employed as the positive controls respectively in the lipase, α-amylase, and α-glucosidase assays. When assayed in the oral starch tolerance test, the extract and fractions also reduced animal glycaemia. UHPLC-DAD-ESI-MS/MS analyses of the extract and fractions led to the identification of 38 phenolic compounds, mainly phenolic acids, ellagitannins and flavonoids, among others, all of them first-time described for the species. CONCLUSION: Based on our findings, T. phaeocarpa has hypoglycaemic activity and polyphenols are the probable bioactive compounds, which support the ethnomedical use of the species.

Asunto(s)

Inhibidores Enzimáticos/farmacología , Hipoglucemiantes/farmacología , Lipasa/antagonistas & inhibidores , Extractos Vegetales/farmacología , Polifenoles/farmacología , Terminalia/química , alfa-Amilasas/antagonistas & inhibidores , Animales , Glucemia/efectos de los fármacos , Brasil , Citocinas/metabolismo , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/uso terapéutico , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Ratones , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Polifenoles/análisis , Polifenoles/aislamiento & purificación , Polifenoles/uso terapéutico , Células THP-1 , alfa-Glucosidasas/efectos de los fármacos , alfa-Glucosidasas/metabolismo

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Plant materials are commonly used in traditional medicine in order to treat various diseases such as Diabetes mellitus. Some plants, such as Syzygium cumini, have the capability to act controlling oxidative stress and protein glycation besides their potential to decrease hyperglycemia and hyperlipidemia by the inhibition of the catalysis of digestive enzymes. The aim of this study was to evaluate the antioxidant and antiglicant activity of S. cumini leaves fractions, their capacity to inhibit hydrolases and lipase enzymes, as well as the cytotoxicity effects against erythrocytes and comparate these results with isolate quercetin flavonoid. MATERIAL AND METHODS: Ethnobotanical researches, carried out by academic studies at the Federal University of Uberlandia, led us to choose S. cumini as a potential plant for treatment of Diabetes mellitus. Fractions from ethanolic extract of S. cumini (hexane/Hex, dichloromethane/DCM, ethyl acetate/EtOAc, n-butanol/ButOH and water/H2O) were used to evaluate their antioxidant (DPPH, ORAC and FRAP) and antiglycant (BSA/fructose, BSA/methylglyoxal and Arginine/Methylglyoxal) activity as well as the inhibitory potential against α-amylase, α-glucosidase and lipase. In addition, identification of the main bioactive compounds of S. cuimini leaves by HPLC-ESIMS/MS analysis was carried out. RESULTS: Our results indicate that all fractions, for exception Hex, present noteworthy antioxidant activity, mainly in EtOAc and ButOH fractions (FRAP 1154.49 ± 67.37 and 1178.27 ± 21.26 µmol trolox eq g-1, respectively; ORAC 1224.63 ± 58.16 and 1313.53 ± 85.23 µmol trolox eq g-1, respectively; DPPH IC50 15.7 ± 2.4 and 23.5 ± 2.7 µg mL-1, respectively). Regarding the antiglycant activity (BSA/fructose and Arginine/Methylglyoxal models), all fraction, for exception Hex, presented inhibition higher than 85%. All fractions were capable to inhibit 100% of α-amylase and the fractions DCM, EtOAc and ButOH inhibited α-glucosidase more than 50%. Regarding the lipase assay, DCM and Hex had the best activity (31.5 ± 14.3 and 44.3 ± 4.5 µg mL-1, respectively). Various biomolecules known as potent antioxidants were identified in these fractions, such as quercetin, kaempferol, luteolin and (Epi)catechin. CONCLUSION: S. cumini fractions and quercetin presented promising antioxidant and antiglycation properties as well as the ability to inhibit digestive enzymes. This study presents new biological activities not yet described for S. cumini which provide new possibilities for further studies in order to assess the antidiabetic potential of S. cumini fractions especially EtOAc and ButOH.

Asunto(s)

Antiinflamatorios/farmacología , Antioxidantes/farmacología , Inhibidores Enzimáticos/farmacología , Hipoglucemiantes/farmacología , Extractos Vegetales/farmacología , Hojas de la Planta , Syzygium , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/toxicidad , Antioxidantes/aislamiento & purificación , Antioxidantes/toxicidad , Cromatografía Líquida de Alta Presión , Digestión/efectos de los fármacos , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/toxicidad , Productos Finales de Glicación Avanzada/antagonistas & inhibidores , Productos Finales de Glicación Avanzada/metabolismo , Inhibidores de Glicósido Hidrolasas/farmacología , Hipoglucemiantes/aislamiento & purificación , Hipoglucemiantes/toxicidad , Lipasa/antagonistas & inhibidores , Lipasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Oxidación-Reducción , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidad , Hojas de la Planta/química , Hojas de la Planta/toxicidad , Ratas Wistar , Espectrometría de Masa por Ionización de Electrospray , Syzygium/química , Syzygium/toxicidad , Espectrometría de Masas en Tándem , alfa-Amilasas/antagonistas & inhibidores , alfa-Amilasas/metabolismo

RESUMEN

The isolation and identification of cholesterol esterase (CE) and pancreatic lipase (PL) inhibitory peptides obtained from the protein hydrolysate of brewer's spent grain (BSG) was performed. BSG peptides were fractionated and purified sequentially by anion exchange, gel filtration (FPLC), and reversed phase high-performance liquid chromatography (RP-HPLC). The fractions obtained from each chromatographic step were collected and the in vitro enzyme inhibitory activity was evaluated. The chromatographic purification process increased the in vitro activities. The most active fractions were evaluated using MALDI-TOF tandem mass spectrometry, which identified three peptides: a peptide with the highest CE inhibition capacity (WNIHMEHQDLTTME) and two peptides with PL inhibition capacity (DFGIASF and LAAVEALSTNG). These three peptides showed hydrophobic and acidic amino acid residues (Asp and Glu) and/or their amines (Asn and Gln), which could be a common feature among lipid-lowering peptides related to CE and PL enzyme inhibition. The in silico studies showed that the three peptides had high hydrophobicity and were susceptible to enzymatic hydrolysis performed by trypsin, pepsin, and pancreatin. The BSG byproduct was a good source of CE and PL inhibitory peptides, thus adding value to this byproduct of the beer industry. This is the first report to demonstrate that BSG peptides can inhibit CE and PL enzymes.

Asunto(s)

Grano Comestible/química , Lipasa/química , Péptidos/química , Esterol Esterasa/química , Cerveza , Cromatografía en Gel , Humanos , Lipasa/antagonistas & inhibidores , Esterol Esterasa/antagonistas & inhibidores , Espectrometría de Masas en Tándem

RESUMEN

The advanced glycation end products (AGEs) constitute a wide variety of substances synthesized from interactions between amino groups of proteins and reducing sugars, which excess induces pathogenesis of chronic diseases. Brazil is the major producer of citrus, a low-cost source of hesperidin, which is a polyphenol recognized for its capacity to inhibit AGEs formation. This is the first work to evaluate the effects of a polyphenolic fraction derived from citrus wastes on the antiglycation and on the inhibition properties of digestive enzymes on the possibility to process these wastes in high value-added products. At concentrations of 10, 15 and 20 mg/mL inhibition of AGEs was higher than 60%. The extracts were able to inhibit by 76% the activity of pancreatic lipase and by 98% the activity of α-glucosidase. For the α-amylase the inhibition capacity was lower than 50%. Strong correlation was obtained among anti-glycation with polyphenolic content and antioxidant capacity.

Asunto(s)

Citrus/química , Inhibidores Enzimáticos/química , Glicósido Hidrolasas/antagonistas & inhibidores , Lipasa/antagonistas & inhibidores , Polifenoles/química , alfa-Amilasas/antagonistas & inhibidores , Animales , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Bovinos , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/farmacología , Productos Finales de Glicación Avanzada/antagonistas & inhibidores , Glicosilación/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Polifenoles/aislamiento & purificación , Polifenoles/farmacología , Saccharomyces cerevisiae/enzimología , Porcinos

RESUMEN

Matricaria chamomilla L. contains antioxidant flavonoids that can have their bioactivity enhanced by enzymatic hydrolysis of specific glycosyl groups. This study implements an untargeted metabolomics approach based on ultra-performance liquid chromatography coupled with electrospray ionisation quadrupole time-of-flight mass spectrometry technique operating in MSE mode (UPLC-QTOF-MSE) and spectrophotometric analysis of chamomile aqueous infusions, before and after hydrolysis by hesperidinase and ß-galactosidase. Several phenolic compounds were altered in the enzymatically treated infusion, with the majority being flavonoid derivatives of apigenin, esculetin, and quercetin. Although enzymatically modifying the infusion only led to a small increase in antioxidant activity (DPPH• method), its inhibitory effect on pancreatic lipase was of particular interest. The enzymatically treated infusion exhibited a greater inhibitory effect (EC50 of 35.6 µM) than unmodified infusion and kinetic analysis suggested mixed inhibition of pancreatic lipase. These results are of great relevance due to the potential of enzymatically treated functional foods in human health.

Asunto(s)

Antioxidantes/farmacología , Inhibidores Enzimáticos/farmacología , Flavonoides/farmacología , Lipasa/antagonistas & inhibidores , Matricaria/química , Antioxidantes/química , Antioxidantes/metabolismo , Compuestos de Bifenilo/antagonistas & inhibidores , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/metabolismo , Flavonoides/química , Flavonoides/metabolismo , Glicósido Hidrolasas/metabolismo , Humanos , Hidrólisis , Lipasa/metabolismo , Matricaria/metabolismo , Metabolómica , Estructura Molecular , Picratos/antagonistas & inhibidores , Relación Estructura-Actividad , beta-Galactosidasa/metabolismo

RESUMEN

Gastrointestinal lipase inhibitors are molecules of pharmaceutical interest due to their use as anti-obesity drugs. In this study, forty strains isolated from soil and sediments were identified with the ability to produce inhibition of gastrointestinal lipase activity. The biomass extract of these strains showed at least 50% inhibition in the hydrolysis of tributyrin by recombinant human pancreatic lipase (rHPL) or rabbit gastric lipase (RGL) by in vitro assays. Based on gene sequencing, the isolates were identified mainly as Streptomycetes. Moreover, none of the identified strains has been reported to be lipase inhibitor producers, so they can be viewed as potential sources for obtaining new drugs. IC50 values of the three best inhibitor extracts showed that AC104-10 was the most promising strain for production of gastrointestinal lipase inhibitors. AC104-10 shows 99% homology (16S rRNA gene fragment) to Streptomyces cinereoruber strain NBRC 12756. An inhibitory study over trypsin activity revealed that AC104-10 extract, as well as THL, had no significant effect on the activity of this protease, showing its specificity for lipases. In addition, analyzes by MALDI-TOF mass spectrometry of the enzyme-inhibitor complex revealed that there is a covalent interaction of the AC104-10 inhibitor with the catalytic serine of the pancreatic lipase, and that the molecular weight of the inhibitor is approximately 686.19 Da.

Asunto(s)

Sedimentos Geológicos/microbiología , Streptomyces/aislamiento & purificación , Actinobacteria/genética , Actinobacteria/aislamiento & purificación , Actinobacteria/metabolismo , Animales , Productos Biológicos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/metabolismo , Humanos , Lagos/microbiología , Lipasa/antagonistas & inhibidores , Lipasa/metabolismo , ARN Ribosómico 16S , Microbiología del Suelo , Streptomyces/genética , Streptomyces/metabolismo

RESUMEN

Bauhinia forficata Link., a cerrado native plant, is used as a complementary treatment for Type 2 Diabetes Mellitus (T2DM). Several studies involving this plant have shown that it has prominent potential to combat hyperglycemia and oxidative stress. Our objective was suggest the phytochemical constitution of fractions of ethanol extract of B. forficata leaves using HPLC-ESI-MS/MS, and evaluates their activities in enzymatic assays to evaluate their inhibitory potential against α-amylase, α-glucosidase and lipase, as well as their antioxidant and anti-glycation capacities. In addition, we evaluated the cytotoxic effects of these fractions using rodents macrophages and erythrocytes. The ETOAC e ButOH fractions showed high polyphenols concentrations, having been determined 11 flavonoids, including the kaempferitrin, the phytomarker of B. forficata Link. In addition, all fractions presented higher antioxidant and antiglycation activities and prominent capacities to digestive enzymes inhibition. On the other hand, in the cellular assays, none fractions showed cytotoxic and hemolytic effects, able to combat the ROS production in macrophages. Thus, this study presented new results on the biological activities of this plant, contributing to the understanding of the action and effectiveness of its use in the management of diabetes mellitus and its complications.

Asunto(s)

Antioxidantes/farmacología , Bauhinia/química , Inhibidores de Glicósido Hidrolasas/farmacología , Hipoglucemiantes/farmacología , Lipasa/antagonistas & inhibidores , Extractos Vegetales/farmacología , Hojas de la Planta/química , Animales , Antioxidantes/química , Supervivencia Celular/efectos de los fármacos , Glicosilación , Hemólisis/efectos de los fármacos , Cinética , Lipasa/metabolismo , Masculino , Ratones Endogámicos C57BL , Fitoquímicos/farmacología , Extractos Vegetales/química , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , alfa-Amilasas/antagonistas & inhibidores , alfa-Amilasas/metabolismo , alfa-Glucosidasas/metabolismo

RESUMEN

Scientific research based on medicinal plants has been highlighted as a complementary treatment to T2DM, stand out the Vochysiaceae family, which have been widely used in folk medicine by traditional South American communities to treat some diseases. Our study aimed to investigate the antioxidant and antiglycation activities of ethanol extracts of leaves (LF) and stem barks (SB) of Vochysiaceae species, evaluated their capacities to inhibit glycoside and lipid hydrolases related to T2DM and molecular identification by HPLC-ESI-MS/MS. Our main findings indicate that the ethanolic extract of four of eight analyzed plants such as LF and SB of Q. grandiflora, Q. parviflora, V. elliptica and Calisthene major exhibited, respectively, potential of α-amylase inhibition (IC50 of LF: 5.7 ±â€¯0.6, 4.1 ±â€¯0.5, 5.8 ±â€¯0.5, 3.2 ±â€¯0.6 and IC50 of SB: 3.3 ±â€¯0.7, 6.2 ±â€¯2.0, 121.0 ±â€¯8.6 and 11.2 ±â€¯2.8 µg/mL), capacities of antioxidant (ORAC of LF: 516.2 ±â€¯0.1, 547.6 ±â€¯4.9, 544.3 ±â€¯6.1, 442.6 ±â€¯2.4 and ORAC of SB: 593.6 ±â€¯22.3, 497.7 ±â€¯0.8, 578 ±â€¯12.3, 593.6 ±â€¯19.5 µmol trolox eq/g; FRAP of LF: 796.1 ±â€¯0.9, 427.7 ±â€¯22.0, 81.0 ±â€¯1.9, 685 ±â€¯37.9 and FRAP of SB: 947.4 ±â€¯24.9, 738.6 ±â€¯24.3, 98.8 ±â€¯7.9, 970.8 ±â€¯13.9 µmol trolox eq/g; DPPH IC50 of LF: 14.2 ±â€¯1.8, 36.3 ±â€¯6.9, 11.8 ±â€¯1.9, 13.3 ±â€¯1.2 and DPPH IC50 of SB: 16.0 ±â€¯3.0, 15.5 ±â€¯1.9, 126.1 ±â€¯23. 6, 5.3 ±â€¯0.3 µg/mL, respectively) and antiglycation (BSA/Frutose IC50 of LF: 43.1 ±â€¯3.4, 52.1 ±â€¯6.0, 175.5 ±â€¯32, 8, 111.8 ±â€¯14.7 and BSA/Frutose IC50 of SB:, 40.1 ±â€¯11.9, 51.2 ±â€¯16. 7, 46.6 ±â€¯5.7, 53.5 ±â€¯13.6 µg/mL) and presence of polyphenols, such as flavonoids and condensed tannins. The extracts presented low ability to inhibit α-glycosidase and lipase enzymes in the initial assays, with values below 40% of inhibition. In BSA/methylglyoxal, only Q. grandiflora SB, V. eliptica LF and V. tucanorum LF showed activity (IC50: 655.5 ±â€¯208.5, 401.9 ±â€¯135.2 and 617.1 ±â€¯80.6 µg/mL, respectively) and only C. major LF and SB, in Arg/methylglyoxal (IC50: 485.1 ±â€¯130.8 and 468.0 ±â€¯150.5 µg/ml, respectively). This study presented new findings about the biological and pharmacological potential of some species of Vochysiaceae family, contributing to the understanding of the action and efficacy in use of these plants, in their management of postprandial hyperglycemia and in glycation and oxidative processes that contribute to managing diabetes mellitus.

Asunto(s)

Antioxidantes/química , Productos Finales de Glicación Avanzada/antagonistas & inhibidores , Inhibidores de Glicósido Hidrolasas/química , Hipoglucemiantes/química , Myrtales/química , Fitoquímicos/química , Antioxidantes/aislamiento & purificación , Evaluación Preclínica de Medicamentos , Pruebas de Enzimas , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Humanos , Hipoglucemiantes/aislamiento & purificación , Lipasa/antagonistas & inhibidores , Fitoquímicos/aislamiento & purificación , Corteza de la Planta/química , Hojas de la Planta/química , alfa-Amilasas/antagonistas & inhibidores

RESUMEN

This work aimed to evaluate the inhibition of Candida rugosa lipase by five guanylhydrazone derivatives through biological, biophysical and theoretical studies simulating physiologic conditions. The compound LQM11 (IC50 = 14.70 µM) presented the highest inhibition against the enzyme. Therefore, for a better understanding of the interaction process, spectroscopic and theoretical studies were performed. Fluorescence and UV-vis assays indicate a static quenching mechanism with non-fluorescent supramolecular complex formation and changing the native protein structure. The binding process was spontaneous (ΔG < 0) and electrostatic forces (ΔH < 0 and ΔS > 0) played a preferential role in stabilizing the complex ligand-lipase. The compounds were classified as non-competitive inhibitors using orlistat as a reference in competition studies. Based on the 1H NMR assays it was possible to propose the sites of ligand (epitope) that bind preferentially to the enzyme and the theoretical studies were consistent with the experimental results. Finally, LQM11 was efficient as a lipase inhibitor of the crude intestinal extract of larvae of Rhynchophorus palmarum, an important agricultural plague, showing potential for control of this pest. Within this context, the real potential of this biotechnological application deserves further studies.

Asunto(s)

Candida/enzimología , Inhibidores Enzimáticos/farmacología , Hidrazonas/farmacología , Lipasa/antagonistas & inhibidores , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Animales , Biotecnología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Hidrazonas/química , Hidrazonas/aislamiento & purificación , Lipasa/metabolismo , Estructura Molecular , Termodinámica , Gorgojos/química

RESUMEN

Different oregano species have been traditionally used as infusions in folk medicine. Oregano medicinal properties, such as antioxidant and anti-inflammatory, have been partially attributed to its polyphenolic content. However, information regarding bioaccessibility of oregano polyphenols is limited. Cell-based antioxidant activity, and in vitro hypoglycemic, and hypolipidemic properties of polyphenolic extracts from three species of oregano species, namely, Hedeoma patens (HP), Lippia graveolens (LG) and Lippia palmeri (LP), subjected to simulated gastrointestinal digestion were evaluated. LC-TOF-MS analysis of HP, LG and LP allowed the identification of 9 flavonoids and 6 hydroxycinnamic acid derivatives with nutraceutical significance. Oregano polyphenolic extracts and digests from HP, LG, and LP exhibited cellular antioxidant capacity, hypoglycemic and hypolipidemic properties. Altogether, our results suggest that HP, LG and LP polyphenols exhibit potential for use as hypoglycemic, hypolipidemic, and antioxidant agents.

Asunto(s)

Antioxidantes/farmacología , Digestión , Inhibidores de Glicósido Hidrolasas/farmacología , Hipolipemiantes/farmacología , Lipasa/antagonistas & inhibidores , Origanum/química , Extractos Vegetales/farmacología , Polifenoles/farmacología , Antioxidantes/aislamiento & purificación , Células CACO-2 , Cromatografía Líquida de Alta Presión , Ácido Gástrico/química , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Humanos , Hipolipemiantes/aislamiento & purificación , Secreciones Intestinales/química , Lipasa/metabolismo , Oxidación-Reducción , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/aislamiento & purificación , Polifenoles/aislamiento & purificación , Espectrometría de Masa por Ionización de Electrospray

RESUMEN

The aqueous and ethanolic extracts of Lippia sidoides Cham. were chemically characterized and tested for their action on enzymes involved in processes such as inflammation, blood coagulation, and digestion. Both extracts potentiated the activity of phospholipases A2 present in the venom of Bothrops atrox in 12 % and completely inhibited the hemolysis induced by B. jararacussu and B. moojeni venoms in the proportions between 1 : 0.5 and 1 : 5 (venom/extracts (w/w)). They inhibited the thrombolysis induced by B. moojeni (10 to 25 %), potentiated the thrombolysis induced by the Lachesis muta muta venom (30 to 80 %), prolonged the coagulation time induced by B. moojeni and L. muta muta venoms, and presented antigenotoxic action. Both extracts reduced the activity of α-glycosidases, the aqueous extract inhibited lipases, and the ethanolic extract inhibited α-amylases. The results demonstrate the modulatory action of the extracts on proteases, phospholipases, and digestive enzymes. In addition, the rich phenolic composition of these extracts highlights their potential for nutraceutical use.

Asunto(s)

Inflamación/tratamiento farmacológico , Lippia/química , Fenoles/farmacología , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Hojas de la Planta/química , Coagulación Sanguínea/efectos de los fármacos , Etanol/química , Glicósido Hidrolasas/antagonistas & inhibidores , Glicósido Hidrolasas/metabolismo , Hemostasis/efectos de los fármacos , Humanos , Inflamación/metabolismo , Lipasa/antagonistas & inhibidores , Lipasa/metabolismo , Lippia/metabolismo , Fenoles/química , Fenoles/metabolismo , Fosfolipasas A2/metabolismo , Fitoquímicos/química , Fitoquímicos/metabolismo , Extractos Vegetales/química , Extractos Vegetales/metabolismo , Hojas de la Planta/metabolismo , Agua/química , alfa-Amilasas/metabolismo

RESUMEN

This study investigated the in vitro and in silico biological properties of the methyl chavicol (MC) and its analogue 2-[(4-methoxyphenyl)methyl]oxirane (MPMO), emphasizing the antioxidant and antilipase effects. MPMO was synthesized from MC that reacted with meta-chloroperbenzoic acid and, after separation and purification, was identified by 1H and 13C NMR and GC-MS. The antioxidant activity was investigated by DPPH, cooxidation ß-carotene/linoleic acid, and thiobarbituric acid assays. With the use of colorimetric determination, the antilipase effect on the pancreatic lipase was tested, while the molecular interaction profiles were evaluated by docking molecular study. MC (IC50 = 312.50 ± 2.28 µg/mL) and MPMO (IC50 = 8.29 ± 0.80 µg/mL) inhibited the DPPH free radical. The inhibition of lipid peroxidation (%) was 73.08 ± 4.79 and 36.16 ± 4.11 to MC and MPMO, respectively. The malonaldehyde content was significantly reduced in the presence of MC and MPMO. MC and MPMO inhibited the pancreatic lipase in 58.12 and 26.93%, respectively. MC and MPMO (-6.1 kcal·mol-1) produced a binding affinity value lower than did diundecylphosphatidylcholine (-5.6 kcal·mol-1). These findings show that MC and MPMO present antioxidant and antilipase activities, which may be promising molecular targets for the treatment of diseases associated with oxidative damage and lipid metabolism.

Asunto(s)

Anisoles/química , Compuestos Epoxi/química , Lipasa/antagonistas & inhibidores , Derivados de Alilbenceno , Anisoles/síntesis química , Anisoles/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Compuestos Epoxi/síntesis química , Compuestos Epoxi/farmacología , Cinética , Lipasa/química , Simulación del Acoplamiento Molecular

RESUMEN

Brazil has the greatest vegetal biodiversity in the world, but products derived from native species are not optimally utilized. Oxalis cordata and Xylopia aromatica are two underutilized species whose leaves and fruits, respectively, have been used as food in the 19th century. In this study, we used chemical and in vitro assays to evaluate the potential of these species as functional foods. The inhibitory activity on pancreatic lipase and DPP-IV were evaluated using the crude extracts and fractions ethyl acetate, butanol and water of these two species. For polyphenols determination, samples were prepared with different solvents and these were analysed by chromatographic and spectroscopic methods. Finally, fatty acids profile was determinated by gas chromatography. The crude extract (IC50=0.84mg/ml), ethyl acetate extract (IC50=0.88mg/ml) an aqueous fraction (IC50=0.63mg/ml) of C. cordata were inhibitory on pancreatic lipase but inactive against dipeptidyl peptidase IV (DPP-IV). Extracts from X. aromatica were inactive against the lipase pancreatic enzyme, but a butanolic fraction inhibited DPP-IV (IC50=0.71±0.05mg/ml). The phenolic acids orientin/isorientin, chlorogenic acid (0.32g/100g) and the flavonoid derivatives rutin (0.27g/100g), quercetin and luteolin were observed in all products. Additionally, fatty acid quantification showed that oleic (7.5g/100g) and linoleic acid (6.5g/100g) were predominant in X. aromatica fruit. This study confirms the potential for the use of both plants as functional foods due to their nutritional value, biological activity and important phytochemical content.

Asunto(s)

Fármacos Antiobesidad/farmacología , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Alimentos Funcionales/análisis , Lipasa/antagonistas & inhibidores , Valor Nutritivo , Oxalidaceae/química , Páncreas/enzimología , Xylopia/química , Fármacos Antiobesidad/química , Fármacos Antiobesidad/aislamiento & purificación , Brasil , Inhibidores de la Dipeptidil-Peptidasa IV/química , Inhibidores de la Dipeptidil-Peptidasa IV/aislamiento & purificación , Frutas/química , Pradera , Lipasa/aislamiento & purificación , Lipasa/metabolismo , Hojas de la Planta/química , Solventes/química

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Plants preparations are used by traditional medicine in the treatment of various diseases, such as type-2 diabetes mellitus. Some medicinal plants are capable of controlling the complications of this metabolic disease at different levels, for example, providing antioxidant compounds that act against oxidative stress and protein glycation and others which are capable of inhibiting the catalysis of digestive enzymes and thus contribute to the reduction of hyperglycemia and hyperlipidemia. Our objective was to investigate the antioxidant and anti-glycation activities of some medicinal plants and their potential inhibitory against α-amylase, α-glucosidase and pancreatic lipase activities. MATERIAL AND METHODS: Based on the ethnobotanical researches carried out by academic studies conducted at the Federal University of Uberlandia, ten plants traditionally used in the treatment of type-2 diabetes mellitus were selected. Ethanol (EtOH) and hexane (Hex) extracts of specific parts of these plants were used in enzymatic assays to evaluate their inhibitory potential against α-amylase, α-glucosidase and lipase, as well as their antioxidant (DPPH, ORAC and FRAP) and anti-glycation (BSA/fructose model) capacities. RESULTS: The results indicate that EtOH extract of four of the ten analyzed plants exhibited more than 70% of antioxidant and anti-glycation capacities, and α-amylase and lipase inhibitory activities; no extract was able to inhibit more than 40% the α-glucosidase activity. The EtOH extracts of Bauhinia forficata and Syzygium. cumini inhibited α-amylase (IC50 8.17 ± 2.24 and 401.8 ± 14.7 µg/mL, respectively), whereas EtOH extracts of B. forficata, Chamomilla recutita and Echinodorus grandiflorus inhibited lipase (IC50 59.6 ± 10.8, 264.2 ± 87.2 and 115.8 ± 57.1 µg/mL, respectively). In addition, EtOH extracts of B. forficata, S. cumini, C. recutita and E. grandiflorus showed, respectively, higher antioxidant capacity (DPPH IC50 0.7 ± 0.1, 2.5 ± 0.2, 1.3 ± 0.2 and 35.3 ± 9.0 µg/mL) and anti-glycation activity (IC50 22.7 ± 4.4, 246.2 ± 81.7, 18.5 ± 2.8 and 339.0 ± 91.0 µg/mL). CONCLUSIONS: EtOH extracts of four of the ten species popularly cited for treatment of type 2 diabetes mellitus have shown promising antioxidant and anti-glycation properties, as well as the ability to inhibit the digestive enzymes α-amylase and lipase. Thus, our results open new possibilities for further studies in order to evaluate the antidiabetic potential of these medicinal plants.

Asunto(s)

Antioxidantes/farmacología , Diabetes Mellitus Tipo 2 , Inhibidores de Glicósido Hidrolasas , Lipasa/antagonistas & inhibidores , Plantas Medicinales/química , alfa-Amilasas/antagonistas & inhibidores , Antioxidantes/química , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Páncreas/enzimología , alfa-Glucosidasas

RESUMEN

Background: Inferior Tieguanyin oolong tea leaves were treated with tannase. The content and bioactivity of catechins in extracts from the treated tea leaves were investigated to assess the improvement in the quality of inferior Tieguanyin oolong tea. Results: Analysis showed that after treatment, the esterified catechin content decreased by 23.5%, whereas non-galloylated catechin and gallic acid contents increased by 15.3% and 182%, respectively. The extracts from tannase-treated tea leaves showed reduced ability to bind to BSA and decreased tea cream levels. The extracts also exhibited increased antioxidant ability to scavenge OH and DPPH radicals, increased ferric reducing power, and decreased inhibitory effects on pancreatic α-amylase and lipase activities. Conclusions: These results suggested that tannase treatment could improve the quality of inferior Tieguanyin oolong tea leaves.

Asunto(s)

Té/enzimología , Hidrolasas de Éster Carboxílico/metabolismo , Té/metabolismo , Té/química , Temperatura , Catálisis , Catequina/análisis , Hojas de la Planta/enzimología , Fermentación , Hidrólisis , Lipasa/antagonistas & inhibidores , Lipasa/metabolismo , Antioxidantes

RESUMEN

The aim of this work was to assess the nutritional and functional components of powder obtained by lyophilization of whole fruits, seeds, pulp and skin from chilto (Solanum betaceum Cav) cultivated in the ecoregion of Yungas, Argentina. The powders have low carbohydrate and sodium content and are a source of vitamin C, carotenoid, phenolics, potassium and fiber. The HPLC-ESI-MS/MS analysis of the fractions enriched in phenolics allowed the identification of 12 caffeic acid derivatives and related phenolics, 10 rosmarinic acid derivatives and 7 flavonoids. The polyphenols enriched extracts before and after simulated gastroduodenal digestion inhibited enzymes associated with metabolic syndrome, including α-glucosidase, amylase and lipase and exhibited antioxidant activity by different mechanisms. None of the analyzed fruit powders showed acute toxicity or genotoxicity. The powders from the three parts of S. betaceum fruit may be a potential functional food and the polyphenol enriched extract of seed and skin may have nutraceutical properties.

Asunto(s)

Frutas/química , Síndrome Metabólico/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Preparaciones de Plantas/farmacología , Semillas/química , Solanum/química , Antioxidantes/análisis , Antioxidantes/farmacología , Argentina , Ácido Ascórbico/análisis , Carotenoides/análisis , Cinamatos/análisis , Depsidos/análisis , Fibras de la Dieta/análisis , Femenino , Flavonoides/análisis , Flavonoides/farmacología , Inhibidores de Glicósido Hidrolasas/análisis , Inhibidores de Glicósido Hidrolasas/farmacología , Humanos , Concentración 50 Inhibidora , Lipasa/antagonistas & inhibidores , Lipasa/metabolismo , Masculino , Fitoquímicos/análisis , Fitoquímicos/farmacología , Preparaciones de Plantas/química , Polifenoles/análisis , Potasio en la Dieta/análisis , Polvos/química , Ingesta Diaria Recomendada , Espectrometría de Masas en Tándem , alfa-Amilasas/antagonistas & inhibidores , alfa-Amilasas/metabolismo , alfa-Glucosidasas/metabolismo , Ácido Rosmarínico

RESUMEN

Phenolics in food and agricultural processing by-products exist in the soluble and insoluble-bound forms. The ability of selected enzymes in improving the extraction of insoluble-bound phenolics from the starting material (experiment I) or the residues containing insoluble-bound phenolics (experiment II) were evaluated. Pronase and Viscozyme improved the extraction of insoluble-bound phenolics as evaluated by total phenolic content, antioxidant potential as determined by ABTS and DPPH assays, and hydroxyl radical scavenging capacity, reducing power as well as evaluation of inhibition of alpha-glucosidase and lipase activities. Viscozyme released higher amounts of gallic acid, catechin, and prodelphinidin dimer A compared to Pronase treatment. Furthermore, p-coumaric and caffeic acids, as well as procyanidin dimer B, were extracted with Viscozyme but not with Pronase treatment. Solubility plays an important role in the bioavailability of phenolic compounds, hence this study may assist in better exploitation of phenolics from winemaking by-products as functional food ingredients and/or supplements.

Asunto(s)

Antioxidantes/farmacología , Inhibidores Enzimáticos/farmacología , Lipasa/antagonistas & inhibidores , Complejos Multienzimáticos/metabolismo , Fenoles/farmacología , Extractos Vegetales/farmacología , Pronasa/metabolismo , alfa-Glucosidasas/química , Antioxidantes/química , Inhibidores Enzimáticos/química , Radical Hidroxilo/química , Fenoles/química , Extractos Vegetales/química , Solubilidad