Polyoxometalates: Study of inhibitory kinetics and mechanism against α-glucosidase

Chi, Guoxiang; Wang, Li; Chen, Bingnian; Li, Jian; Hu, Jingjing; Liu, Shuxia; Zhao, Ming-Lang; Ding, Xiaomei; Li, Yue

doi:10.1016/j.jinorgbio.2019.110784

Cited by 19 publications

(18 citation statements)

References 41 publications

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“…The conventional antidiabetic therapies have been proven effective despite the fact that the use of some of them is costive and may be associated with serious side effects [ 7 ]. Cost, side effects, and the general belief that conventional drugs are synthetic and for that matter unsafe compared to herbal medicines, which are thought to be “natural” and relatively safe have contributed to the renewed interest in the use of herbs and herb-derived products for the treatment and management of human diseases including DM [ 8 , 9 ]. This paradigm is quiet common in poorer tropical countries of the world, where most people rely on herbal medicine to meet their primary health care needs [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Abrus precatorius Leaf Extract Reverses Alloxan/Nicotinamide-Induced Diabetes Mellitus in Rats through Hormonal (Insulin, GLP-1, and Glucagon) and Enzymatic (α-Amylase/α-Glucosidase) Modulation

Boye

Barku

Acheampong

et al. 2021

BioMed Research International

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Background. Abrus precatorius is used in folk medicine across Afro-Asian regions of the world. Earlier, glucose lowering and pancreato-protective effects of Abrus precatorius leaf extract (APLE) was confirmed experimentally in STZ/nicotinamide-induced diabetic rats; however, the underlying mechanism of antidiabetic effect and pancreato-protection remained unknown. Objective. This study elucidated antidiabetic mechanisms and pancreato-protective effects of APLE in diabetic rats. Materials and Methods. APLE was prepared by ethanol/Soxhlet extraction method. Total phenols and flavonoids were quantified calorimetrically after initial phytochemical screening. Diabetes mellitus (DM) was established in adult Sprague-Dawley rats (weighing 120–180 g) of both sexes by daily sequential injection of nicotinamide (48 mg/kg; ip) and Alloxan (120 mg/kg; ip) over a period of 7 days. Except control rats which had fasting blood glucose (FBG) of 4.60 mmol/L, rats having stable FBG (16–21 mmol/L) 7 days post-nicotinamide/Alloxan injection were considered diabetic and were randomly reassigned to one of the following groups (model, APLE (100, 200, and 400 mg/kg, respectively; po) and metformin (300 mg/kg; po)) and treated daily for 18 days. Bodyweight and FBG were measured every 72 hours for 18 days. On day 18, rats were sacrificed under deep anesthesia; organs (kidney, liver, pancreas, and spleen) were isolated and weighed. Blood was collected for estimation of serum insulin, glucagon, and GLP-1 using a rat-specific ELISA kit. The pancreas was processed, sectioned, and H&E-stained for histological examination. Effect of APLE on enzymatic activity of alpha (α)-amylase and α-glucosidase was assessed. Antioxidant and free radical scavenging properties of APLE were assessed using standard methods. Results. APLE dose-dependently decreased the initial FBG by 68.67%, 31.07%, and 4.39% compared to model (4.34%) and metformin (43.63%). APLE (100 mg/kg) treatment restored weight loss relative to model. APLE increased serum insulin and GLP-1 but decreased serum glucagon relative to model. APLE increased both the number and median crosssectional area (×106μm2) of pancreatic islets compared to that of model. APLE produced concentration-dependent inhibition of α-amylase and α-glucosidase relative to acarbose. APLE concentration dependently scavenged DPPH and nitric oxide (NO) radicals and demonstrated increased ferric reducing antioxidant capacity (FRAC) relative to standards. Conclusion. Antidiabetic effect of APLE is mediated through modulation of insulin and GLP-1 inversely with glucagon, noncompetitive inhibition of α-amylase and α-glucosidase, free radical scavenging, and recovery of damaged/necro-apoptosized pancreatic β-cells.

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Section: Introductionmentioning

confidence: 99%

Abrus precatorius Leaf Extract Reverses Alloxan/Nicotinamide-Induced Diabetes Mellitus in Rats through Hormonal (Insulin, GLP-1, and Glucagon) and Enzymatic (α-Amylase/α-Glucosidase) Modulation

Boye

Barku

Acheampong

et al. 2021

BioMed Research International

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“…Thus, POMs exhibit outstanding physical, chemical, and biochemical properties that remain to be completely understood and applied. Due to these properties, POMs are studied in environmental, chemical, and industrial fields, particularly in the areas of catalysis, corrosion prevention, smart glasses, and macromolecular crystallography, as well as in biology, such as for cancer treatment, bacterial infection, and diabetes, among others [1][2][3][4][5][6]. Although the number of POM studies with anticancer effects is increasing, their mechanisms of action in each type of cancer cell are still far from being understood [3].…”

Section: Introductionmentioning

confidence: 99%

“…Although the number of POM studies with anticancer effects is increasing, their mechanisms of action in each type of cancer cell are still far from being understood [3]. The antitumor activity of these inorganic compounds seems to be caused, at least in part, by the inhibition of certain enzymes such as alkaline phosphatases, kinases, ecto-nucleotidases, glucosidases, and P-type ATPases [5][6][7][8]. Moreover, some POMs are also understood to interfere with mitochondria function and DNA, while others can exert an immunomodulatory activity [9,10].…”

Section: Introductionmentioning

confidence: 99%

The Aquaporin-3-Inhibiting Potential of Polyoxotungstates

Pimpão

Silva

Mósca

et al. 2020

IJMS

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Polyoxometalates (POMs) are of increasing interest due to their proven anticancer activities. Aquaporins (AQPs) were found to be overexpressed in tumors bringing particular attention to their inhibitors as anticancer drugs. Herein, we report for the first time the ability of polyoxotungstates (POTs), such as of Wells–Dawson P2W18, P2W12, and P2W15, and Preyssler P5W30 structures, to affect aquaporin-3 (AQP3) activity and impair melanoma cell migration. The tested POTs were revealed to inhibit AQP3 function with different effects, with P2W18, P2W12, and P5W30 being the most potent (50% inhibitory concentration (IC50) = 0.8, 2.8, and 3.2 µM), and P2W15 being the weakest (IC50 > 100 µM). The selectivity of P2W18 toward AQP3 was confirmed in yeast cells transformed with human aquaglyceroporins. The effect of P2W12 and P2W18 on melanoma cells that highly express AQP3 revealed an impairment of cell migration between 55% and 65% after 24 h, indicating that the anticancer properties of these compounds may in part be due to the blockage of AQP3-mediated permeability. Altogether, our data revealed that P2W18 strongly affects AQP3 activity and cancer cell growth, unveiling its potential as an anticancer drug against tumors where AQP3 is highly expressed.

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“…α-glucosidase is a key enzyme that affects human metabolism, so α-glucosidase is considered to be an important target for the treatment of non-insulin dependent diabetes. 22 By inhibiting the activity of α-glucosidase, the absorption and release of carbohydrates in the intestine slow down and the level of postprandial blood glucose is reduced. 23 Most researchers at home and abroad prepare α-glucosidase inhibitors by extracting natural active components from plants or synthesizing phenolic hydroxyl derivatives.…”

Section: α-Glucosidasementioning

confidence: 99%

“…At present, the research group has obtained preliminary results in the study of the inhibitory effect of polyoxometalates on α-glucosidase. Chi et al 22,23 have found that Keggin type POMs, which is replaced by transition metal, and vanadium substituted Dawson type POMs are effective and competitive inhibitors of α-glucosidase. In addition, they have micro-molar inhibitory effect on α-glucosidase.…”

Section: α-Glucosidasementioning

confidence: 99%