In Vitro Inhibition of Pancreatic Lipase by Polyphenols: A Kinetic, Fluorescence Spectroscopy and Molecular Docking Study

Martinez-Gonzalez, Alejandra I.; ́Álvarez-Parrilla, Emilio; Díaz‐Sánchez, Ángel G.; Rosa, Laura A. de la; Núñez‐Gastélum, José Alberto; Vazquez-Flores, Alma A.; González‐Aguilar, Gustavo A.

doi:10.17113/ftb.55.04.17.5138

Cited by 126 publications

(94 citation statements)

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“…Pancreatic lipase is involved predominantly with the breakdown of dietary lipids and their assimilation in the intestine; hence, pancreatic lipase inhibitors are used to prevent the absorption of fats in the diet, making them ideal for the management of obesity or overweight [35][36][37]. Previous reports have suggested that polyphenols such as caffeic acid, p-coumaric acid, quercetin, and capsaicin from hot peppers are good pancreatic lipase inhibitors [38]. The inhibitory activities of PP4 and PP6 indicate the importance of L. tetragona in the control of lipid deposition in the body and ultimately in the management of diabetes.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Antidiabetic Activity Affecting Glucose Uptake in HepG2 Cells Following Their Exposure to Extracts of Lauridia tetragona (L.f.) R.H. Archer

Odeyemi

Dewar

2019

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The incidence of diabetes is on the rise and one of the medically active plants used for the treatment of diabetes in South Africa is Lauridia tetragona. The aim of this study is to investigate the antidiabetic property of the polyphenolics (PP) compounds isolated from the methanolic extract of Lauridia tetragona. The α-amylase, α-glucosidase, dipeptidyl peptidase IV (DPPIV), lipase inhibitory activities, and glucose uptake in HepG2 were investigated. The methanolic extract fractions of L. tetragona yielded six fractions (PP1-PP6) all of which showed weak inhibition against DPPIV and lipase compared to the standards. However, PP4 and PP6 showed the best inhibition against α-amylase (IC 50 of 359.3 ± 2.11 and 416.82 ± 2.58 µg/mL, respectively) and α-glucosidase (IC 50 of 95.93 ± 2.34 and 104.49 ± 2.21 µg/mL, respectively) and only PP4 (173.6%) resulted in enhanced glucose uptake in HepG2 cells compared to berberine (129.89%) and metformin (187.16%) used as positive controls. The previous investigation on PP4 and PP6 showed the presence of polyphenolics such as ferulic acid, coumaric acid, and caffeic acid. The results of this study suggest that L. tetragona could be suitable as an antidiabetic agent and justifies the folkloric use of the plant to treat diabetes.

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Section: Discussionmentioning

confidence: 99%

In Vitro Antidiabetic Activity Affecting Glucose Uptake in HepG2 Cells Following Their Exposure to Extracts of Lauridia tetragona (L.f.) R.H. Archer

Odeyemi

Dewar

2019

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“…La inhibición de la actividad de la enzima lipasa pancreática se realizó de acuerdo a Martinez-Gonzalez et al (2017a). La lipasa se disolvió en una disolución amortiguadora Tris 20 mM (pH = 7.2), a una concentración final de 2.0 mg/mL.…”

Section: Análisis De La Actividad Enzimática De Lipasa Pancreáticaunclassified

“…La disminución de su actividad enzimática por inhibidores reversibles, como los polifenoles, es objeto de estudio ya que podrían eliminar los efectos secundarios de un inhibidor no reversible (Sakulnarmrat y Konczak, 2012). Se ha reportado una actividad inhibitoria en valores de IC 50 (concentración del ligando a la cual se inhibe la mitad de la actividad enzimática), más eficiente para flavonoides como la quercetina, en comparación con ácidos fenólicos como el ácido caféico (Martinez-Gonzalez et al, 2017a). Extractos vegetales ricos en flavonoides como QUE han sido evaluados por su elevada actividad inhibitoria frente a lipasa (Sakulnarmrat y Konczak, 2012), pero no se les había asociado con su estructura.…”

Section: Introductionunclassified

Inhibición de lipasa pancreática por flavonoides: importancia del doble enlace C2=C3 y la estructura plana del anillo C//Inhibition of pancreatic lipase by flavonoids: relevance of the C2=C3 double bond and C-ring planarity

et al. 2020

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Lipasa pancreática es una enzima clave en el metabolismo de lípidos. Los flavonoides son compuestos bioactivos de gran relevancia debido a sus interacciones con enzimas digestivas. Se evaluó la actividad de lipasa pancreática en presencia de flavonoides. Mediante espectroscopía UVVisible se determinó que el mejor inhibidor fue quercetina, seguido de rutina > luteolina > catequina > hesperetina, con valores de IC50 de 10.30, 13.50, 14.70, 28.50 y 30.50 μM, respectivamente. Todos los flavonoides mostraron una inhibición mixta, excepto catequina que mostró una inhibición acompetitiva. La capacidad inhibitoria de los flavonoides se relacionó con propiedades estructurales compartidas entre los distintos flavonoides, como la hidroxilación en las posiciones C5, C7 (anillo A), C2’ y C3’ (anillo B), y el doble enlace entre C2 y C3 (anillo C). Los resultados de inhibición coincidieron con el análisis de la fluorescencia extrínseca. Los estudios de docking molecular indicaron que la interacción entre lipasa pancreática y los flavonoides fue principalmente mediante interacciones hidrofóbicas (pi-stacking). Las interacciones de todos los flavonoides, excepto rutina, se dieron en el mismo sitio (subsitio 1) de la enzima. La insaturación entre C2 y C3 fue determinante para el acomodo de los flavonoides con la enzima, principalmente por interacciones de pi-stacking.ABSTRACTPancreatic lipase is a key enzyme in lipid metabolism. Flavonoids are bioactive compounds obtained from vegetables with big relevance, due to their intrinsic interaction with digestive enzymes. Pancreatic lipase activity was evaluated in the presence of flavonoids, through UV-Vis spectroscopy. All tested flavonoids showed a mixed-type inhibition, except catechin, which showed a uncompetitive inhibition. The best inhibitor was quercetin followed by rutin > luteolin > catechin > hesperetin, with IC50 values of 10.30, 13.50, 14.70, 28.50 and 30.50 μM, respectively. The flavonoids inhibitory capacity was related to structural properties shared between the different flavonoids, such as the hydroxylation at C5, C7 (ring A), C2’ and C3’ (ring B), and the double bond between C2 and C3 (ring C). The inhibition results are in agreement with the extrinsic fluorescence analysis. Molecular docking studies indicated that the interaction between pancreatic lipase and flavonoids was mainly through hydrophobic interactions (pi-stacking). The interactions of all flavonoids, except rutin, occurred at the same enzyme site (subsite 1). Instauration between C2 and C3 was decisive for the arrangement of flavonoids with the enzyme, mainly due to pi-stacking interactions.

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“…This enzyme has been intensely studied because of its relation to anti– obesity treatments (5, 6). In addition to myricetin, some other flavonoids have been proposed to be lipase inhibitors, for example it has been shown that quercetin can bind to lipase near the active site (7). Many of these studies are based on molecular docking, where the flavonoids are considered soluble compounds and the interaction happens at the molecular level.…”

Section: Introductionmentioning

confidence: 99%

Interaction between myricetin aggregates and lipase under simplified intestinal conditions

Bustos

Håkansson

Linares-Pastén

et al. 2019

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telephone number: +46 46 222 83 03 2 13 Abstract 14 Myricetin, a flavonoid found in the plant kingdom, has previously been identified as a food 15 molecule with beneficial effects against obesity. This property has been related with its potential 16 to inhibit lipase, the enzyme responsible of fat digestion. In this study we investigate the 17 interaction between myricetin and lipase under simplified intestinal conditions from a colloidal 18 point of view. The results show that myricetin form aggregates in aqueous medium and under 19 simplified intestinal condition, where it was found that lipase is in its monomeric form. Although 20 lipase inhibition by myricetin at a molecular level has been reported previously, the results of this 21 study suggest that myricetin aggregates inhibit lipase by a sequestering mechanism as well. The 22 size of these aggregates was determined to be in the range of a few nm to >200 nm. 1. Introduction24 Myricetin is a polyphenol member of the flavonoids family. It is commonly found in the plant 25 kingdom and present in a diversity of foods such as berries, teas and wines (1, 2). Besides its anti-26 oxidant properties, myricetin has been claimed to display several beneficial activities such as 27 analgesic, anti-inflammatory, antitumor, and antidiabetic activities (3). As other compounds of 28 the same family, myricetin can inhibit several digestive enzymes (4), for example lipase, the main 29 enzyme in fat digestion. This enzyme has been intensely studied because of its relation to anti-30 obesity treatments (5, 6). In addition to myricetin, some other flavonoids have been proposed to 31 be lipase inhibitors, for example it has been shown that quercetin can bind to lipase near the 32 active site (7). Many of these studies are based on molecular docking, where the flavonoids are 33 considered soluble compounds and the interaction happens at the molecular level. On the other 3 34 hand, other studies have shown that some flavonoids can aggregate in aqueous media and inhibit 35 proteins by a sequestering mechanism (8, 9).36 The myricetin content in some edible products is higher than its aqueous solubility, for instance 37 green tea has been reported to contain approximately 6 μg of myricetin per ml (10), whereas the 38 aqueous solubility is <1.5 μg/mL (11). Thus, it is likely that the majority of the molecules are not 39 present as dissolved compounds and that they could be present as, for instance, supramolecular 40 aggregates. The presence of myricetin aggregates in solution, can influence enzymatic assays. 41 Bustos et al. (2019), have shown that the presence of phenolic aggregates can affect the 42 reproducibility of lipase assays. Pohjala et al. (2012) have also discussed this issue and suggested 43 that this disturbance can be reduced by adding surfactants that reduce aggregate formation 44 when using enzymatic assays in the presence of flavonoids.45 A challenge to applications trying to harness the many beneficial effects of myricetin is its low 46 bioavailability; 10% absolute ...

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In Vitro Inhibition of Pancreatic Lipase by Polyphenols: A Kinetic, Fluorescence Spectroscopy and Molecular Docking Study

Cited by 126 publications

References 42 publications

In Vitro Antidiabetic Activity Affecting Glucose Uptake in HepG2 Cells Following Their Exposure to Extracts of Lauridia tetragona (L.f.) R.H. Archer

In Vitro Antidiabetic Activity Affecting Glucose Uptake in HepG2 Cells Following Their Exposure to Extracts of Lauridia tetragona (L.f.) R.H. Archer

Inhibición de lipasa pancreática por flavonoides: importancia del doble enlace C2=C3 y la estructura plana del anillo C//Inhibition of pancreatic lipase by flavonoids: relevance of the C2=C3 double bond and C-ring planarity

Interaction between myricetin aggregates and lipase under simplified intestinal conditions

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