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1.
Food Chem ; 333: 127478, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32663752

RESUMO

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.


Assuntos
Moringa oleifera/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Células 3T3-L1 , Animais , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Lipase/antagonistas & inibidores , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos
2.
Food Chem ; 329: 127168, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32512395

RESUMO

A polyphenols-rich extract was obtained from polyvinylpolypyrrolidone (PVPP) winery residue, and its neuroprotective effects and ability to modulate the kinetics of type 2 diabetes-relevant enzymes were characterized. The PVPP-white wine extract is a mixture of polyphenols (840.08 ± 161.25 µg/mg, dry weight) dominated by proanthocyanidins and hydroxycinnamic acids, affording strong antioxidant activity, as detected by the protection of membrane lipids against oxidation and superoxide radical anion scavenging activity. Regarding type 2 diabetes framework, the extract inhibits α-glucosidase (Ki = 166.9 µg/mL) and aldose reductase (Ki = 127.5 µg/mL) through non-competitive mechanisms. Despite the modest ability to inhibit rat brain acetylcholinesterase, it protects neuronal SH-SY5Y cells against oxidative damage promoted by glutamate, decreasing reactive oxygen species generation and preserving cell redox state. Thus, PVPP-white wine extract has potential to support the development of functional foods and/or nutraceuticals aiming neuroprotection and glucose homeostasis regulation, with high relevance in Alzheimers disease and type 2 diabetes interlink.


Assuntos
Diabetes Mellitus Tipo 2/enzimologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Povidona/análogos & derivados , Vinho , Acetilcolinesterase , Aldeído Redutase/metabolismo , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular , Proteínas Ligadas por GPI/antagonistas & inibidores , Ácido Glutâmico/toxicidade , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Síndromes Neurotóxicas/genética , Síndromes Neurotóxicas/prevenção & controle , Oxirredução , Extratos Vegetais/química , Polifenóis/análise , Polifenóis/farmacologia , Povidona/química , Proantocianidinas/química , Proantocianidinas/farmacologia , Ratos , Vinho/análise
3.
Food Chem ; 324: 126847, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32344340

RESUMO

This study aimed to investigate the inhibitory effect of chestnut inner skin extract (CISE) on the activity of postprandial blood sugar-related enzymes. In total, 12 flavonoids were identified by HPLC-TOF-MS. CISE showed strong and weak inhibition on α-amylase and α-glucosidase, with the IC50 of 27.2 and 2.3 µg/mL, respectively. The inhibition modes of CISE against α-amylase and α-glucosidase were mixed-type and non-competitive type, respectively. Epicatechin gallate noncompetitively inhibited α-amylase, α-glucosidase and dipeptidyl peptidase IV (DPP-IV). Analysis by ultraviolet-visible spectroscopy, fluorescence spectroscopy and circular dichroism suggested that flavonoids altered the hydrophobicity and microenvironment of these enzymes. CISE decreased the starch bioavailability by reducing the enzymatic hydrolysis rate and increasing the fraction of undigested starch. The extract reduced the rapidly digestible starch and increased the resistant starch after incorporation into A-, B- or C- crystallinity starch. Thus, the chestnut inner skin is a useful resource for regulating postprandial blood sugar level.


Assuntos
Inibidores da Dipeptidil Peptidase IV/farmacologia , Fagaceae/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Extratos Vegetais/farmacologia , Disponibilidade Biológica , Catequina/análogos & derivados , Catequina/farmacologia , Dipeptidil Peptidase 4/química , Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/química , Flavonoides/análise , Inibidores de Glicosídeo Hidrolases/química , Nozes/química , Extratos Vegetais/química , Amido/farmacocinética , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/química , alfa-Glucosidases/química
4.
BMC Complement Med Ther ; 20(1): 72, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32143602

RESUMO

BACKGROUND: Flavonoids from plant medicines are supposed to be viable alternatives for the treatment of type 2 diabetes (T2D) as less toxicity and side effects. Radix scutellariae (RS) is a widely used traditional medicine in Asia. It has shown great potential in the research of T2D. However, the pharmacological actions remain obscured due to the complex chemical nature of plant medicines. METHODS: In the present study, a systematic method combining ultrafiltration UPLC-TripleTOF-MS/MS and network pharmacology was developed to screen α-glucosidase inhibitors from flavonoids of RS, and explore the underlying mechanism for the treatment of T2D. RESULTS: The n-butanol part of ethanol extract from RS showed a strong α-glucosidase inhibition activity (90.55%, IC50 0.551 mg/mL) against positive control acarbose (90.59%, IC50 1.079 mg/mL). A total of 32 kinds of flavonoids were identified from the extract, and their ESI-MS/MS behaviors were elucidated. Thirteen compounds were screened as α-glucosidase inhibitors, including viscidulin III, 2',3,5,6',7-pentahydroxyflavanone, and so on. A compound-target-pathway (CTP) network was constructed by integrating these α-glucosidase inhibitors, target proteins, and related pathways. This network exhibited an uneven distribution and approximate scale-free property. Chrysin (k = 87), 5,8,2'-trihydroxy-7-methoxyflavone (k = 21) and wogonin (k = 20) were selected as the main active constituents with much higher degree values. A protein-protein interaction (PPI) weighted network was built for target proteins of these α-glucosidase inhibitors and drug targets of T2D. PPARG (Cd = 0.165, Cb = 0.232, Cc = 0.401), ACACB (Cd = 0.155, Cb = 0.184, Cc = 0.318), NFKB1 (Cd = 0.233, Cb = 0.161, Cc = 0.431), and PGH2 (Cd = 0.194, Cb = 0.157, Cc = 0.427) exhibited as key targets with the highest scores of centrality indices. Furthermore, a core subnetwork was extracted from the CTP and PPI weighted network. Type II diabetes mellitus (hsa04930) and PPAR signaling pathway (hsa03320) were confirmed as the critical pathways. CONCLUSIONS: These results improved current understanding of natural flavonoids on the treatment of T2D. The combination of ultrafiltration UPLC-TripleTOF-MS/MS and network pharmacology provides a novel strategy for the research of plant medicines and complex diseases.


Assuntos
Flavonoides/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Extratos Vegetais/farmacologia , Scutellaria baicalensis/química , China , Cromatografia Líquida de Alta Pressão , Flavonoides/química , Inibidores de Glicosídeo Hidrolases/química , Espectrometria de Massas , Extratos Vegetais/química , Ultrafiltração
5.
Food Chem ; 317: 126346, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32070843

RESUMO

The inhibitory mechanisms of ferulic acid against α-amylase and α-glucosidase were investigated by enzyme kinetic analysis, circular dichroism (CD), Fourier-transform infrared (FT-IR) spectroscopy, fluorescence quenching and molecular docking. Results indicated that ferulic acid strongly inhibited α-amylase (IC50: 0.622 mg ml-1) and α-glucosidase (IC50: 0.866 mg ml-1) by mixed and non-competitive mechanisms, respectively. CD spectra and fluorescence intensity measurements confirmed that the secondary structure of α-amylase and α-glucosidase were changed and the microenvironments of certain amino acid residues were modulated by the binding of ferulic acid. FT-IR spectra indicated that the interaction between ferulic acid and α-amylase/α-glucosidase mainly involved in non-covalent bonds. Molecular docking further demonstrated that the interaction forces between ferulic acid and α-amylase/α-glucosidase were hydrogen bonds, with the binding energy of -5.30 to -5.10 and -5.70 kcal mol-1, respectively. This study might provide a theoretical basis for the designing of novel functional foods with ferulic acid.


Assuntos
Ácidos Cumáricos/metabolismo , Inibidores de Glicosídeo Hidrolases/metabolismo , alfa-Amilases/metabolismo , alfa-Glucosidases/metabolismo , Sítios de Ligação , Ácidos Cumáricos/química , Inibidores de Glicosídeo Hidrolases/química , Ligação de Hidrogênio , Cinética , Simulação de Acoplamento Molecular , Estrutura Secundária de Proteína , Termodinâmica , alfa-Amilases/química , alfa-Glucosidases/química
6.
J Enzyme Inhib Med Chem ; 35(1): 565-573, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31969031

RESUMO

Embelin is a naturally occurring para-benzoquinone isolated from Embelia ribes (Burm. f.) of the Myrsinaceae family. It was first discovered to have potent inhibitory activity (IC50 = 4.2 µM) against α-glucosidase in this study. Then, four series of novel embelin derivatives were designed, prepared and evaluated in α-glucosidase inhibition assays. The results show that most of the embelin derivatives synthesised are effective α-glucosidase inhibitors, with IC50 values at the micromolar level, especially 10d, 12d, and 15d, the IC50 values of which are 1.8, 3.3, and 3.6 µM, respectively. Structure-activity relationship (SAR) studies suggest that hydroxyl groups in the 2/5-position of para-benzoquinone are very important, and long-chain substituents in the 3-position are highly preferred. Moreover, the inhibition mechanism and kinetics studies reveal that all of 10d, 12d, 15d, and embelin are reversible and mixed-type inhibitors. Furthermore, docking experiments were carried out to study the interactions between 10d and 15d with α-glucosidase.


Assuntos
Benzoquinonas/farmacologia , Desenho de Fármacos , Inibidores de Glicosídeo Hidrolases/farmacologia , alfa-Glucosidases/metabolismo , Benzoquinonas/síntese química , Benzoquinonas/química , Relação Dose-Resposta a Droga , Embelia/química , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/química , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade
7.
Phytochemistry ; 171: 112232, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31911266

RESUMO

Corni Fructus, also known as the fruit of Cornus officinalis Sieb. et Zucc., has long been used as a traditional Chinese medicine and is widely consumed as a nutritional food in the form of function drink and wine. Recently, Corni Fructus has attracted considerable interest because of its anti-diabetic effects. A systematic phytochemical investigation of Corni Fructus was performed to find anti-diabetic components, which led to the isolation of 10 unreported iridoid glycosides, cornusdiglycosides A-J (1-8, 9a/9b and 10a/10b). Their chemical structures were determined through spectroscopic analysis (ultraviolet [UV], infrared [IR], high-resolution electrospray ionisation mass spectroscopy [HRESIMS], one-dimensional [1D] and two-dimensional [2D] nuclear magnetic resonance [NMR]). Such morroniside-type diglycosides were first reported from natural sources, and all isolates were evaluated for α-glucosidase inhibitory activity. The results showed that all compounds (1-10) exhibited α-glucosidase (from Saccharomyces cerevisiae) inhibitory activities with IC50 values ranging from 78.9 ± 4.09 to 162.2 ± 9.17 µM, whereas acarbose, the positive control, displayed α-glucosidase inhibitory activity with IC50 value of 118.9 ± 7.89 µM.


Assuntos
Cornus/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Glicosídeos/farmacologia , Glucosídeos Iridoides/farmacologia , Compostos Fitoquímicos/farmacologia , alfa-Glucosidases/metabolismo , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Glicosídeos/química , Glicosídeos/isolamento & purificação , Humanos , Glucosídeos Iridoides/química , Glucosídeos Iridoides/isolamento & purificação , Conformação Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação
8.
J Agric Food Chem ; 68(6): 1555-1562, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31986026

RESUMO

Passiflora edulis Sims (passion fruit) seeds are often discarded as byproducts during juice processing. In fact, the seeds are of considerable commercial value in the food and cosmetics industry because of their rich polyphenols, especially piceatannol. In this study, high-speed countercurrent chromatography (HSCCC) was applied for the separation of stilbene polyphenols from passion fruit seeds. The n-hexane-ethyl acetate-methanol-water (1:2:1:2.8, v/v) was found to be the optimum two-phase solvent for the preparation of two major stilbenes, scirpusin B (8) and piceatannol (9) with purities of 90.2% and 94.8%, respectively. In addition, a continuous semipreparative HPLC was applied to further purify the HSCCC fractions containing minor stilbenes and obtain four new piceatannol derivatives (1-4) along with three known ones (5-7). The structures of these new compounds were determined using spectroscopic methods, including NMR, high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and circular dichroism (CD). The isolated compounds were evaluated for α-glucosidase inhibitory activities in vitro. The result suggested that all of them exhibited more significant activity than acarbose, and passiflorinol B (2) had the strongest activity, with a IC50 value of 1.7 µM.


Assuntos
Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Passiflora/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Estilbenos/química , Estilbenos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Distribuição Contracorrente , Frutas/química , Sementes/química , alfa-Glucosidases/química
9.
Carbohydr Polym ; 230: 115586, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887942

RESUMO

α-Glycosidase is an essential target for the management of postprandial serum glucose in diabetic patients. Therefore, the interest has been growing in the screening of α-glycosidase inhibitor from natural resource. In the present study, the structure and α-glycosidase inhibitory activity of a polysaccharide (named as ACPP-1) from Aconitum coreanum were investigated. Based on the results from high performance gel permeation chromatography, GC-MS and 1D/2D nuclear magnetic resonance spectroscopy, ACPP-1 was a highly-linear polysaccharide with a molecular weight of 34.0 kD and containing over 90 % of glucose. It was composed of (1→4)-α-d-Glcp and α-Araf. ACPP-1 exhibited a dose-dependent inhibitory eff ;ect against α-glycosidase activity in vitro and the IC50 value was ∼0.8 mg/mL. In oral starch tolerance test, treatment with ACPP-1 (800 mg/kg) significantly improved the starch tolerance in mice. Taken together, this study provided a potential intervention and management for postprandial hyperglycemia by the polysaccharide fraction from A. coreanum.


Assuntos
Aconitum/química , Inibidores de Glicosídeo Hidrolases/química , Polissacarídeos/química , alfa-Glucosidases/química , Animais , Cromatografia em Gel , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Camundongos , Peso Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Polissacarídeos/ultraestrutura , alfa-Glucosidases/farmacologia , alfa-Glucosidases/ultraestrutura
10.
Int J Biol Macromol ; 148: 722-736, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31972201

RESUMO

The natural form of wild edible fungus is the fruiting body. The cultivation of fruiting bodies from sexual reproduction requires strict conditions and long periods. Some literatures have paid attentions on the mycelia prepared with liquid fermentation to alter fruiting bodies. Cordyceps militaris (C. militaris) is a kind of precious edible fungus. The polysaccharide is an important active ingredient in C. militaris. The manuscript aimed to evaluate the feasibility of alternative of mycelia to fruit bodies with studies of polysaccharides from C. militaris of different developmental stages. The two polysaccharides were separated. The chemical structure and inhibitory activity on α-glucosidase of polysaccharides were explored. The results indicated that the structure and inhibitory activity on α-glucosidase of polysaccharides with different developmental stages had significant differences. The polysaccharides from fruiting bodies had better inhibitory activity on α-glucosidase. It demonstrated that the mycelia of C. militaris from asexual reproduction with liquid fermentation can't be an effective substitute for fruiting bodies from sexual reproduction, from the perspective of polysaccharides.


Assuntos
Cordyceps/química , Inibidores de Glicosídeo Hidrolases/química , Polissacarídeos/química , alfa-Glucosidases/metabolismo , Fermentação , Carpóforos/química , Micélio/química , Conformação Proteica , Relação Estrutura-Atividade , Viscosidade
11.
Biosci Biotechnol Biochem ; 84(3): 598-605, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31724491

RESUMO

Red kidney beans (Phaseolus vulgaris L.) contain bioactive compounds that are known to exhibit antidiabetic effects via inhibition of α-glucosidase. However, information on the nonpolar components that exhibit antidiabetic activity is limited. Here, we report the isolation and structure determination of components with α-glucosidase inhibitory activity, which were obtained from the hexane extract of red kidney beans. Triacylglycerols (TAGs) were identified as the major components exhibiting inhibitory activity against α-glucosidase. The chemical structure of TAGs was determined by a combination of GC-MS and UPLC-MS/MS. The primary TAGs identified were LnLnLn (trilinolenin) and LnLLn (1,3-dilinolenoyl-2-linoleoyl glycerol). The major fatty acids present in these TAGs were α-linolenic acid (ω-3) and linoleic acid (ω-6). These TAGs were also found to inhibit the α-glucosidase activity in a similar fashion as acarbose. These results suggest that TAGs have potency as antidiabetics and support the potential suitability of red kidney beans for diabetes treatment.


Assuntos
Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Hexanos/química , Phaseolus/química , Triglicerídeos/isolamento & purificação , Cromatografia Líquida/métodos , Diabetes Mellitus/tratamento farmacológico , Ácidos Graxos/análise , Cromatografia Gasosa-Espectrometria de Massas , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/uso terapêutico , Estrutura Molecular , Espectrometria de Massas em Tandem , Triglicerídeos/química
12.
Fitoterapia ; 140: 104442, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31790769

RESUMO

Averrhoa carambola L. (Oxalidaceae) was widely cultivated for fruits (star fruit), whereas the value of leaves remains to be discovered. Our study on the leaves yielded five flavan-3-ols (1-5) and two 2-diglycosyloxybenzoates. Their structures were determined by spectroscopic and chemical methods. Epicatechin-(5,6-bc)-4ß-(p-hydroxyphenyl)-dihydro-2(3H)-pyranone (1) and benzyl 2-ß-d-apiofuranosyl-(1 â†’ 6)-ß-d-glucopyranosyloxybenzoate (6) were new structures. 6-(S-2-Pyrrolidinone-5-yl)epicatechin (4) and 6-(R-2-pyrrolidinone-5-yl)epicatechin (5) were obtained as monomeric diastereomer for the first time and their absolute configurations were determined by electronic circular dichroism (ECD) computation. Epicatechin-(7,8-bc)-4α-(p-hydroxyphenyl)-dihydro-2(3H)-pyranone (2), epicatechin-(7,8-bc)-4ß-(p-hydroxyphenyl)-dihydro-2(3H)-pyranone (3), and methyl 2-ß-d-apiofuranosyl-(1 â†’ 6)-ß-d-glucopyranosyloxybenzoate (7) were not previously reported from the genus Averrhoa. Compounds 1-5 showed more potent 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical cation and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities and ferric reducing antioxidant power (FRAP) than l-ascorbic acid. Meanwhile 1 and 3 exhibited lipase and α-glucosidase inhibitory activities, respectively. The results clarified the structures of flavan-3-ols and 2-diglycosyloxybenzoates in the leaves and their antioxidant, lipase, and α-glucosidase inhibitory activities.


Assuntos
Antioxidantes/química , Averrhoa/química , Benzoatos/química , Flavonoides/química , Folhas de Planta/química , Antioxidantes/isolamento & purificação , Benzoatos/isolamento & purificação , China , Flavonoides/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Lipase/antagonistas & inibidores , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação
13.
Biomed Chromatogr ; 34(1): e4705, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31629370

RESUMO

Lithocarpus polystachyus leaves exhibit antidiabetic activity and is consumed as a herbal tea in China. In this study, phytochemical profiles of L. polystachyus leaves were identified and characterized by ultra-high-performance liquid chromatography-quadrupole time-of-flight-MS in both positive and negative ion modes. A total of 17 compounds were tentatively characterized and identified by accurate mass and characteristic fragment ions. The total phenolic contents in the leaf extracts ranged from 9.0 to 13.4 g gallic acid equivalents/100 g of dry weight (DW). In addition, the effect of these extracts on inhibiting the activities of α-glucosidase and protein tyrosine phosphatase 1B (PTP1B) were evaluated. L. polystachyus extracts demonstrated significant inhibition of α-glucosidase (more than 88.1% at a concentration of 1.25 mg/mL) and acarbose (93.6% at a concentration of 5 mg/mL) while the PTP1B inhibition rate was over 84.3%. The antioxidant capacities of the leaf extracts were determined using 2,2-diphenyl-1-picrylhydrazyl, ABTS, and ferric reducing ability of plasma methods and ranged from 50.5 to 72.5 g trolox, from 43.2 to 77.7 g trolox, and from 5.0 to 10.6 g butylated hydroxytoluene (BHT; equaling trolox or BHT per 100 g of DW), respectively. Based on these results, L. polystachyus can be considered as a functional food owing to its antidiabetic and antioxidative activities, which are attributed to its rich phenolic and dihydrochalcone contents.


Assuntos
Fagaceae , Compostos Fitoquímicos , Extratos Vegetais , Antioxidantes , Cromatografia Líquida de Alta Pressão/métodos , Inibidores de Glicosídeo Hidrolases/química , Humanos , Espectrometria de Massas/métodos , Fenóis/análise , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/química , Extratos Vegetais/análise , Extratos Vegetais/química , Folhas de Planta/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores
14.
Phytochemistry ; 170: 112192, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31726325

RESUMO

Chemical fractionation of the ethanolic extract of Eclipta prostrata yielded a series of unreported terpenoid constituents, including a rare 6/6/6/6-fused tetracyclic triterpenoid, a pentacyclic triterpenoid, two pentacyclic triterpenoid saponins, a diterpenoid and a sesquiterpenoid. Structures were assigned to these compounds on the basis of comprehensive spectroscopic analyses, with the absolute configurations of the tetracyclic triterpenoid, the diterpenoid and the sesquiterpenoid being determined via explanation of electronic circular dichroism data. Screening of these isolates in an array of bioassays revealed antibacterial, cytotoxic and α-glucosidase inhibitory activities for selective compounds. Of particular interest, the tetracyclic triterpenoid showed very strong inhibition against α-glucosidase with an IC50 of 0.82 ±â€¯0.18 µM, being 103-fold as active as the positive control acarbose.


Assuntos
Antibacterianos/farmacologia , Eclipta/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Neoplasias/tratamento farmacológico , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Terpenos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Bacillus subtilis/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Células HeLa , Humanos , Testes de Sensibilidade Microbiana , Neoplasias/patologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Staphylococcus aureus/efeitos dos fármacos , Terpenos/química , Terpenos/isolamento & purificação , alfa-Glucosidases/metabolismo
15.
Eur J Med Chem ; 186: 111831, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31740052

RESUMO

Heparanase is regarded as a promising target for anticancer drugs and Ronepastat is one of the most promising heparanase inhibitors insert in clinical study for Multiple Myeloma Therapy. To improve its pharmacokinetic/pharmacodynamic profile, as well to have an antidote able to neutralize its activity in case of over dosages or intolerance, a new class of its derivatives was obtained inserting non-carbohydrate moieties of different length between the polysaccharide chain and biotin or its derivatives. In vitro these novel derivatives maintain the anti-heparanase activity without induced toxicity. The newly synthesized compounds retained the ability to attenuate the growth of CAG myeloma tumors in mice with potency similar, or in one case even higher than that of the reference compound Roneparstat as well as inhibited metastatic dissemination (lung colonization) of murine B16-F10 melanoma cells in vivo.


Assuntos
Antineoplásicos/farmacologia , Biotina/química , Glucuronidase/antagonistas & inibidores , Glicóis/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Heparina/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Glucuronidase/metabolismo , Glicóis/síntese química , Glicóis/química , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/química , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Imagem Óptica , Relação Estrutura-Atividade
16.
Nat Prod Res ; 34(3): 369-377, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30600701

RESUMO

The crude polysaccharide extracted from Cordyceps militaris was chemically modified to obtain carboxymethylated derivatives (CM-CPS) and acetylated derivatives (AC-CPS). The physicochemical characterizations were comparatively investigated by chemical methods, high-performance gel permeation chromatography, FT-IR spectra, NMR analysis, Congo red test, scanning electron microscopy, atomic force microscopy and differential scanning calorimetry. Then α-glucosidase inhibitory activities were conducted to determine the structure-bioactivity relationship. Results indicated that carboxymethylation and acetylation modification of polysaccharide were successful with the carboxymethyl substitutions might being C-6, C-2 and acetyl substitutions at C-3, C-6 inferred from NMR analysis. In addition, the tertiary structure, ultrastructure, melting properties were also different from native polysaccharide. Besides, α-glucosidase inhibitory activities of derivatives exhibited differently with CM-CPS to be the lowest. Therefore, it was concluded that change of structure in polysaccharide had certain effect on bioactivity with degree of substitution and substituents position being the influence factors.


Assuntos
Cordyceps/química , Polissacarídeos/química , alfa-Glucosidases/efeitos dos fármacos , Acetilação , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/farmacologia , Metilação , Polissacarídeos/isolamento & purificação , Espectroscopia de Infravermelho com Transformada de Fourier
17.
Food Chem ; 302: 125373, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31442706

RESUMO

The aim of this work was to investigate and compare the phenolic profile of 15 wild growing blackthorn (Prunus spinosa L.) genotypes from the slopes of Fruska Gora mountain in north Serbia. Their effect in inhibiting i) α-amylase and α-glucosidase activities and ii) colorectal cancer cell line (HT29) growth was also studied. Blackthorn fruit extracts exhibited high phenolic content being enrich in anthocyanins. Principal component analysis was used to correlate the bioactive response with phenolic composition. It was found that derivatives quercetin and anthocyanin peonidin are the major contributors of the inhibition of carbohydrates hydrolyzing enzymes as well as with the antiproliferative effect of blackthorn. Among all samples, the genotype from Beska locality showed the higher capacity in inhibiting alpha-amylase, alpha-glucosidase and HT29 cell growth. Because of high anthocyanin content and higher bioactive response, these genotypes could be recommended for the further cultivation and investigation.


Assuntos
Polifenóis/análise , Prunus/química , Prunus/genética , Antocianinas/análise , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/análise , Ácido Clorogênico/análogos & derivados , Ácido Clorogênico/análise , Cromatografia Líquida de Alta Pressão , Análise de Alimentos/estatística & dados numéricos , Frutas/química , Genótipo , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Células HT29 , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Análise de Componente Principal , Quercetina/análise , Ácido Quínico/análogos & derivados , Ácido Quínico/análise , Sérvia , alfa-Amilases/antagonistas & inibidores
18.
J Sci Food Agric ; 100(2): 509-516, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31487036

RESUMO

BACKGROUND: Emblica officinalis, known as amla in Ayurveda, has been used as a folk medicine to treat numerous pathological conditions, including diabetes. However, the novel extract of E. officinalis fruit extract (amla fruit extract, AFE, Saberry®) containing 100 g kg-1 ß-glucogallin along with hydrolyzable tannins has not yet been extensively studied for its antidiabetic potential. OBJECTIVE: The aim of this study was to investigate the antidiabetic and antioxidant activities of AFE and its stability during gastric stress as well as its thermostability. METHODS: The effect of AFE on the inhibition of pancreatic α-amylase and salivary α-amylase enzymes was studied using starch and yeast α-glucosidase enzyme using 4-nitrophenyl α-d-glucopyranoside as substrate. Further, 2,2-diphenyl-1-picrylhydrazyl radical scavenging and reactive oxygen species inhibition assay was performed against AFE. RESULTS: AFE potently inhibited the activities of α-amylase and α-glucosidase in a concentration-dependent manner with half maximal inhibitory concentration (IC50 ) values of 135.70 µg mL-1 and 106.70 µg mL-1 respectively. Furthermore, it also showed inhibition of α-glucosidase (IC50 562.9 µg mL-1 ) and dipeptidyl peptidase-4 (DPP-4; IC50 3770 µg mL-1 ) enzyme activities. AFE is a potent antioxidant showing a free radical scavenging activity (IC50 2.37 µg mL-1 ) and protecting against cellular reactive oxygen species (IC50 1.77 µg mL-1 ), and the effects elicited could be attributed to its phytoconstituents. CONCLUSION: AFE showed significant gastric acid resistance and was also found to be thermostable against wet heat. Excellent α-amylase, α-glucosidase, and DPP-4 inhibitory activities of AFE, as well as antioxidant activities, strongly recommend its use for the management of type 2 diabetes mellitus. © 2019 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Antioxidantes/química , Inibidores da Dipeptidil Peptidase IV/química , Frutas/química , Inibidores de Glicosídeo Hidrolases/química , Phyllanthus emblica/química , Extratos Vegetais/química , Antioxidantes/isolamento & purificação , Diabetes Mellitus Tipo 2/enzimologia , Dipeptidil Peptidase 4/química , Inibidores da Dipeptidil Peptidase IV/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Extratos Vegetais/isolamento & purificação , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/química , alfa-Glucosidases/química
19.
Eur J Med Chem ; 188: 111974, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31883489

RESUMO

A series of 28 novel 1,2,3-triazole hybrids of myrrhanone B have been designed and synthesized by employing regioselective Cu catalyzed Huisgen 1,3-dipolar cycloaddition reaction in highly efficient manner. All the synthesized analogues were assessed for their antiproliferative potential against A549 (Lung), DU145 (Prostate), MDA-MB-231 (Breast), SiHa (Cervical), U87MG (Glioblastoma), PC-3 (Prostate), HT-29 (Colon), L132 (Normal lung) cell lines. Further, the synthesized hybrids have also been screened for anti-inflammatory activity (TNF-α and IL-1ß) and α-glucosidase inhibitory activity. The biological results revealed that compound 11 (meta hydroxy phenyl 1,2,3-triazole) and compound 29 (deoxyuridine 1,2,3-triazole) found to be the most potent antiproliferative ones against PC-3 cell line. Compound 11 (IC50: 6.57 ± 0.62 µM) showed six folds more potent than parent compound 1 (IC50: 40.67 ± 2.2 µM) and displayed almost identical inhibitory activity with standard doxorubicin (IC50: 5.05 ± 0.25 µM), whereas compound 29 (IC50: 10.85 ± 0.90 µM) exhibited four folds more potent than parent myrrhanone B (1). In view of potent activity of compounds 11 and 29 they have been subjected to detailed flowcytometry analysis. Compound 29 treated cells significantly increased the SubG1 population of cells indicative of apoptosis compared to compound 11. Further, the results of anti-inflammatory studies indicated that compounds 3, 6, 9, 27, 28, 29 and 30 exhibited significant inhibitory activity against both TNF-α and IL-1ß than the parent compound 1. Interestingly, compound 27 exhibited good activity towards inflammatory cytokines TNF-α (IC50: 7.83 ± 0.95 µM). Interestingly, α-glucosidase inhibitory assay results revealed that compounds 14 (IC50: 2.77 ± 0.59 µM) and 16 (IC50: 4.12 ± 0.77 µM) as the most potent ones. In fact, compound 14 exhibited highest activity and found to be several times more potent than the parent compound 1 as well as standard acarbose (IC50: 2124 ± 170 µM).


Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Commiphora/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Triazóis/farmacologia , Triterpenos/farmacologia , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/química , Humanos , Estrutura Molecular , Resinas Vegetais , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/química , Triterpenos/síntese química , Triterpenos/isolamento & purificação
20.
Molecules ; 24(23)2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31783621

RESUMO

Twenty-one natural and unnatural phenolic compounds containing a carbohydrate moiety were synthesized and their structure-activity relationship (SAR) was evaluated for α-glucosidase inhibition and antioxidative activity. Varying the position of the galloyl unit on the 1,5-anhydro-d-glucitol (1,5-AG) core resulted in changes in the α-glucosidase inhibitory activity and notably, particularly strong activity was demonstrated when the galloyl unit was present at the C-2 position. Furthermore, increasing the number of the galloyl units significantly affected the α-glucosidase inhibition, and 2,3,4,6-tetra-galloyl-1,5-AG (54) and 2,3,4,6-tetra-galloyl-d-glucopyranose (61) exhibited excellent activities, which were more than 13-fold higher than the α-glucosidase inhibitory activity of acertannin (37). Moreover, a comparative structure-activity study suggested that a hemiacetal hydroxyl functionality in the carbohydrate core and a biaryl bond of the 4,6-O-hexahydroxydiphenoyl (HHDP) group, which are components of ellagitannins including tellimagrandin I, are not necessary for the α-glucosidase inhibitory activity. Lastly, the antioxidant activity increased proportionally with the number of galloyl units.


Assuntos
Antioxidantes/química , Inibidores de Glicosídeo Hidrolases/química , Polifenóis/química , alfa-Glucosidases , Antioxidantes/síntese química , Antioxidantes/farmacologia , Carboidratos/química , Desoxiglucose/química , Ácido Gálico/análogos & derivados , Ácido Gálico/síntese química , Ácido Gálico/química , Glucosídeos/síntese química , Glucosídeos/química , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/farmacologia , Estrutura Molecular , Extratos Vegetais/química , Polifenóis/síntese química , Polifenóis/farmacologia , Relação Estrutura-Atividade , alfa-Glucosidases/química
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