Natural Prenylchalconaringenins and Prenylnaringenins as Antidiabetic Agents: α-Glucosidase and α-Amylase Inhibition and in Vivo Antihyperglycemic and Antihyperlipidemic Effects

Abstract

Inhibition of α-glucosidase and α-amylase decreases postprandial blood glucose levels and delays glucose absorption, making it a treatment strategy for type 2 diabetes. This study examined in vivo and in vitro antidiabetic activities of natural prenylchalconaringenins 1 and 2 and prenylnaringenins 3 and 4, found in hops and beer. 3'-Geranylchalconaringenin (2) competitively and irreversibly inhibited α-glucosidase (IC = 1.08 μM) with activity 50-fold higher than that of acarbose (IC = 51.30 μM) and showed moderate inhibitory activity against α-amylase (IC = 20.46 μM). Docking analysis substantiated these findings. In addition, compound 2 suppressed the increase in postprandial blood glucose levels and serum levels of total cholesterol and triglycerides in streptozotocin-induced diabetic mice. Taken together, these results suggest that 2 has dual inhibitory activity against α-glucosidase and α-amylase and alleviates diabetic hyperglycemia and hyperlipidemia, making it a potential functional food ingredient and drug candidate for management of type 2 diabetes.

Screening of Musa balbisiana Colla. seeds for antidiabetic properties and isolation of apiforol, a potential lead, with antidiabetic activity

“…Also, hyperglycaemic condition results in the formation of excess AGEs, which further triggers diabetic‐associated complications. So the consumption of foods that contain potential α ‐glucosidase and α ‐amylase inhibitors can effectively control postprandial blood sugar levels, and thus represents a dietary solution for the management of type 2 diabetes . In this context, plant extracts and their active components have always attracted much attention, as a natural alternative over synthetic medicines, for more effective and safe inhibition of unregulated secretion of digestive enzymes .…”

A study towards drug discovery for the management of type 2 diabetes mellitus through inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by chalcone derivatives

“…The compounds were divided as chalcones 1-28, with the 1,3-diarylprop-2-en-1-one framework, and chalcone analogues 29-41, known as cinnamylideneacetophenones, which hold two double bonds linking the A and B rings. In the first set of compounds (1-28), one is unsubstituted (1), four are hydroxylated (2-5), ten are hydroxylated and methoxylated (6)(7)(8)(9)(10)(11)(12)(13)(14)(15), two are only methoxylated (16,17), two display methyl substituents (18,19), two display nitro groups (20,21) and seven possess chloro substituents (22)(23)(24)(25)(26)(27)(28). Among the chalcone analogues (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41), one is unsubstituted (29), eleven present a single substitution, including methyl (30,36), methoxy (31,37), chloro (32), fluoro (33), bromo (34), nitro (35,38,39) and hydroxy…”

“…16,17 Over the last years, increasing attention has been dedicated to chalcones, due to their simple chemistry, ease of synthesis, diversity of substituents, safety, and a vast number of recognized biological activities, including anti-bacterial, anti-parasitic, anti-fungal, anti-viral, anti-cancer, anti-inflammatory, antioxidant, anti-allergic, anti-obesity, anti-hypertensive and antidiabetic activities. 15,18,19 Several reports even indicate that some chalcones are able to inhibit the enzymes α-amylase [20][21][22][23][24] and α-glucosidase. 20,22,[25][26][27][28][29] However, differences found in the experimental conditions regarding this topic, together with the fact that the authors usually constrained the study to a limited number of compounds with decreased rational drug design, make the comparison among the available studies difficult and consequently the establishment of an accurate structure-activity relationship (SAR).…”

“…15,18,19 Several reports even indicate that some chalcones are able to inhibit the enzymes α-amylase [20][21][22][23][24] and α-glucosidase. 20,22,[25][26][27][28][29] However, differences found in the experimental conditions regarding this topic, together with the fact that the authors usually constrained the study to a limited number of compounds with decreased rational drug design, make the comparison among the available studies difficult and consequently the establishment of an accurate structure-activity relationship (SAR). With this aim, the inhibitory activity of a panel of twenty-eight chalcones and thirteen chalcone analogues against α-amylase and α-glucosidase, a total of forty-one structurally related scaffolds (Table 1), most of them being studied here for the first time, is assessed.…”

Untitled

“…Pharmacological Activities of Chalcones: The biological effects of chalcones were found to be dependent on the presence, the number and position of functional groups such as methoxy, glycosides, hydroxyl, halogens in both A and B rings 75 . They present a broad spectrum of biological activities such as antifungal 76 , antifilarial, larvicidal, anticonvulsant 66 , anticancer 77,78 , antiinflammatory 79 , neuroprotective 79 , antimalarial 80 , antibacterial 81 , antilipidemic 82 , antihyperglycemic 82 , antiviral 83 , antimycobacterial 84 , antiprotozoal (antileishmanial and antitrypanosoma) 85 , antiangiogenic 86 , antiplatelet 87 , anti-HIV 88 and Two chalconoids from the desert plant Pulicaria incisa prevented cell death by inhibiting reactive oxygen species (ROS) 89 . The chalcones showed selective, reversible and potent MAO-B inhibition compared to MAO-A.…”