RESUMEN
The inhibition of α-glucosidase and glycation is considered as an effective approach for the treatment of type 2 diabetes. In this study, multispectroscopic and molecular docking techniques were employed to investigate the inhibition of tannic acid on α-glucosidase and glycation. Kinetics analyses revealed that tannic acid had a significant inhibition on α-glucosidase (IC50â¯=â¯0.35⯱â¯0.02⯵M) in a reversible and mixed competitive manner. The results acquired from fluorescence quenching and ANS-binding fluorescence methods revealed that tannic acid could bind to α-glucosidase and reduce the hydrophobic area on the surface of the enzyme. In addition, synchronous fluorescence analysis showed that tannic acid decreased the hydrophobicity of α-glucosidase and changed the conformation of the enzyme. In vitro glycation assays showed that tannic acid had strong inhibitory effects on the formation of fructosamine, dicarbonyl compounds, and fluorescent AGEs. ANS-binding fluorescence analysis showed that tannic acid could bind to BSA and reduce the hydrophobicity of BSA in glycation. Moreover, the results of molecular docking showed the interaction between tannic acid and α-glucosidase was mainly driven by hydrogen bond, electrostatic, and hydrophobic interaction. And the interaction between tannic acid and BSA was mainly driven by hydrogen bond and hydrophobic interaction.
Asunto(s)
Inhibidores de Glicósido Hidrolasas/farmacología , Taninos/farmacología , alfa-Glucosidasas/metabolismo , Inhibidores de Glicósido Hidrolasas/química , Glicosilación , Enlace de Hidrógeno , Modelos Moleculares , Estructura Molecular , Conformación Proteica , Taninos/químicaRESUMEN
Condensed tannins contained in food are known to have many beneficial impacts on human health. In this study, we attempt to evaluate the structural features, antityrosinase effects, anti-melanogenesis properties, antioxidant activity and DNA damage protection activity of condensed tannins purified from the seeds of Vigna angularis (Willd.) Ohwi et Ohashi. MALDI-TOF MS, ESI-Full-MS, and HPLC-ESI-MS demonstrated that condensed tannins are composed of procyanidins, prodelphinidins and their gallates, among which procyanidins are the dominant components. As reversible and mixed-type inhibitors of tyrosinase, condensed tannins from V. angularis strongly inhibited the monophenolase and odiphenolase activities with IC50 values of 130.0 ± 0.5 and 35.1 ± 2.0 µg mL-1, respectively. What's more, condensed tannins had a good inhibitory effect on cell proliferation, cellular tyrosinase activity, and melanogenesis of B16 mouse melanoma cells. Based on fluorescence quenching analyses, these compounds were determined to be effective quenchers of the enzyme and its substrates. According to molecular docking, the strong interaction between condensed tannins and tyrosinase was mainly driven by hydrogen bonding and hydrophobic force. In addition, condensed tannins showed a powerful antioxidant capacity and DNA damage protection activity. Therefore, condensed tannins from V. angularis have feasible applications in food, medicine, and the cosmetics industry.
Asunto(s)
Antioxidantes/farmacología , Daño del ADN/efectos de los fármacos , Melaninas/metabolismo , Extractos Vegetales/farmacología , Proantocianidinas/farmacología , Sustancias Protectoras/farmacología , Vigna/química , Animales , Antioxidantes/química , Línea Celular , Humanos , Melanoma , Ratones , Estructura Molecular , Monofenol Monooxigenasa/antagonistas & inhibidores , Monofenol Monooxigenasa/metabolismo , Extractos Vegetales/química , Proantocianidinas/química , Sustancias Protectoras/química , Semillas/química , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
α-Glucosidase is a critical enzyme associated with diabetes mellitus, and the inhibitors of the enzyme play important roles in the treatment of the disease. In this study, the inhibitory effect and mechanism of rifampicin on α-glucosidase were investigated by multispectroscopic methods along with molecular docking technique. The results showed that rifampicin inhibited α-glucosidase activity prominently (IC50â¯=â¯135⯱â¯1.2⯵M) in a reversible and competitive-type manner. The fluorescence intensity of α-glucosidase was quenched by rifampicin through forming rifampicin-α-glucosidase complex in a static procedure. And the formation of the rifampicin-α-glucosidase complex was driven spontaneously by hydrophobic forces and hydrogen bonds. The results obtained from molecular docking further indicated that hydrophobic forces were formed between rifampicin and amino acid residues Phe 173, Pro151, and hydrogen bonds were generated by the interactions of rifampicin with residues Ser 180, Asn 414, Gly160, and Gly161 of α-glucosidase. Moreover, it was found that the binding of rifampicin to α-glucosidase could alter the conformation of the enzyme to make it steady, and the binding distance was estimated to be 1.02â¯nm. Therefore, this study confirmed a novel α-glucosidase inhibitor and possibly contributed to the improvement of newfangled anti-diabetic agent.
Asunto(s)
Inhibidores de Glicósido Hidrolasas/metabolismo , Inhibidores de Glicósido Hidrolasas/farmacología , Simulación del Acoplamiento Molecular , Rifampin/metabolismo , Rifampin/farmacología , alfa-Glucosidasas/metabolismo , Sitios de Unión , Transferencia de Energía , Cinética , Conformación Proteica , Análisis Espectral , Termodinámica , alfa-Glucosidasas/químicaRESUMEN
Omeprazole was first evaluated for its antityrosinase activity and preservation of fresh-cut apples. The results obtained from enzymic analyses showed that the omeprazole inhibited tyrosinase activity (IC50â¯=â¯40⯱â¯1.2⯵M) with a reversible and competitive mechanism. Fluorescence quenching assays demonstrated that the interaction between omeprazole and tyrosinase was driven by hydrophobic forces and hydrogen bonds in a static procedure. Molecular docking further revealed that hydrogen bonds and hydrophobic forces were generated by omeprazole with the amino acid residues located in the A chain of tyrosinase. Moreover, the results from preservation assays showed that omeprazole could inhibit the activities of polyphenol oxidase (PPO) and peroxidase (POD), prevent the oxidation of total phenolics and flavonoid, thereby delay the browning of fresh-cut apples. Hence, this work identified a novel tyrosinase inhibitor and expands its feasible application as a food preservative.
Asunto(s)
Conservación de Alimentos/métodos , Malus/enzimología , Monofenol Monooxigenasa/antagonistas & inhibidores , Omeprazol/farmacología , Agaricus/enzimología , Catecol Oxidasa/metabolismo , Dihidroxifenilalanina/metabolismo , Flavonoides/análisis , Cinética , Malus/efectos de los fármacos , Simulación del Acoplamiento Molecular , Omeprazol/química , Peroxidasa/metabolismo , Fenoles/análisis , Soluciones , Espectrometría de Fluorescencia , Especificidad por SustratoRESUMEN
This study investigated the structure, antioxidant activity, antityrosinase activity and mechanism of proanthocyanidins from mung bean seed [Vigna radiata (L.) Wilczek]. The structural composition were characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), electrospray ionization-full-mass spectrometry (ESI-Full-MS), and high-pressure liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS) techniques. The mung bean seed proanthocyanidins were composed of procyanidins, prodelphinidins, and their rhamnosides. According to enzyme kinetic analysis, these compounds were potent, reversible, and mixed-type inhibitors of tyrosinase. They inhibited the enzyme activity by interacting with enzyme as well as substrates. The results of molecular docking showed that the interaction between mung bean seed proanthocyanidins and tyrosinase was driven by hydrogen bond, hydrophobic and electrostatic interactions. In addition, mung bean seed proanthocyanidins were demonstrated as powerful antioxidants. Therefore, this study confirmed a novel tyrosinase inhibitor and would lay a scientific foundation for their utilization in pharmaceutical and food industries.
Asunto(s)
Antioxidantes/farmacología , Inhibidores Enzimáticos/farmacología , Monofenol Monooxigenasa/antagonistas & inhibidores , Proantocianidinas/farmacología , Vigna/química , Antioxidantes/química , Cromatografía Líquida de Alta Presión/métodos , Inhibidores Enzimáticos/química , Cinética , Simulación del Acoplamiento Molecular , Estructura Molecular , Monofenol Monooxigenasa/química , Monofenol Monooxigenasa/metabolismo , Proantocianidinas/química , Semillas/química , Semillas/metabolismo , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
In this study, the content, structure, antityrosinase activity, and mechanism of longan bark condensed tannins were evaluated. The findings obtained from mass spectrometry demonstrated that longan bark condensed tannins were mixtures of procyanidins, propelargonidins, prodelphinidins, and their acyl derivatives (galloyl and p-hydroxybenzoate). The enzyme analysis indicated that these mixtures were efficient, reversible, and mixed (competitive is dominant) inhibitor of tyrosinase. What's more, the mixtures showed good inhibitions on proliferation, intracellular enzyme activity and melanogenesis of mouse melanoma cells (B16). From molecular docking, the results showed the interactions between inhibitors and tyrosinase were driven by hydrogen bond, electrostatic, and hydrophobic interactions. In addition, high levels of total phenolic and extractable condensed tannins suggested that longan bark might be a good source of tyrosinase inhibitor. This study would offer theoretical basis for the development of longan bark condensed tannins as novel food preservatives and medicines of skin diseases.