Three flavonoids from tartary buckwheat bran, namely, quercetin (Que), isoquercetin (Iso) and rutin (Rut), have been evaluated as α-glucosidase inhibitors by fluorescence spectroscopy and enzymatic ...kinetics and have also been compared with the market diabetes healer, acarbose. The results indicated that Que, Iso and Rut could bind α-glucosidase to form a new complex, which exhibited a strong static fluorescence quenching via nonradiation energy transfer, and an obvious blue shift of maximum fluorescence. The sequence of binding constants (K A) was Que > Iso > Rut, and the number of binding sites was one for all of the three cases. The thermodynamic parameters were obtained by calculations based on data of binding constants. They revealed that the main driving force of the above-mentioned interaction was hydrophobic. Enzymatic kinetics measurements showed that all of the three compounds were effective inhibitors against α-glucosidase. Inhibitory modes all belonged to a mixed type of noncompetitive and anticompetitive. The sequence of affinity (1/K i) was in accordance with the results of binding constants (K A). The concentrations which gave 50% inhibition (IC50) were 0.017 mmol·L−1, 0.185 mmol·L−1 and 0.196 mmol·L−1, compared with acarbose’s IC50 (0.091 mmol·L−1); the dose of acarbose was almost five times of that of Que and half of that of Iso and Rut. Our results explained why the inhibition on α-glucosidase of tartary buckwheat bran extractive substance (mainly Rut) was much weaker than that of its hydrolysis product (a mixture of Que, Iso and Rut). This work would be significant for the development of more powerful antidiabetes drugs and efficacious utilization of tartary buckwheat, which has been proved as an acknowledged food in the diet of diabetic patients.
The studies on natural compounds to diabetes mellitus treatment have been increasing in recent years. Research suggests that natural components can inhibit alpha-glucosidase activities, an important ...strategy in the management of blood glucose levels. In this work, for the first time in the literature, the compounds produced by
Ganoderma lipsiense
extracts were identified and evaluated on the inhibitory effect of these on alpha-glucosidase activity. Four phenolic compounds were identified by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) to crude extract from
G. lipsiense
grown in red rice medium (RCE) and synthetic medium (SCE), being syringic acid identified in both extracts. Gas chromatography-mass spectrometry (GC-MS) analysis showed fatty acids and their derivatives, terpene, steroid, niacin, and nitrogen compounds to
SCE
, while
RCE
was rich in fatty acids and their derivatives. Both extracts demonstrated alpha-glucosidase inhibition (
RCE
IC
50
= 0.269 ± 8.25 mg mL
−1
;
SCE
IC
50
= 0.218 ± 9.67 mg mL
−1
), and the purified hexane fraction of
RCE
(
RHEX
) demonstrated the highest inhibition of enzyme (81.1%). Studies on kinetic inhibition showed competitive inhibition mode to
RCE
, while
SCE
showed uncompetitive inhibition mode. Although the inhibitory effects of
RCE
and
SCE
were satisfactory, the present findings identified some unpublished compounds to
G. lipsiense
in the literature with important therapeutic properties.
Inhibitors of the enzymes dipeptidyl peptidase (DPP)-IV and α-glucosidase are two classes of pharmacotherapeutic agents used for the treatment of type 2 diabetes. In the present study, whey protein ...isolate (WPI), α-lactalbumin, β-lactoglobulin, serum albumin, and lactoferrin hydrolysates obtained by peptic digestion were investigated for their potential to serve as natural sources of DPP-IV and α-glucosidase inhibitors. Although inhibition of DPP-IV activity was observed in all pepsin-treated whey proteins studied, the α-lactalbumin hydrolysate showed the greatest potency with an IC50 value of 0.036 mg/mL. Conversely, only WPI, β-lactoglobulin, and α-lactalbumin hydrolysates displayed some inhibitory activity against α-glucosidase. This study suggests that peptides generated from whey proteins may have dual beneficial effects on glycemia regulation and could be used as functional food ingredients for the management of type 2 diabetes.
Shenqi Jiangtang Granule, a well‐known traditional Chinese herbal preparation, has been widely used for the treatment of type II diabetes mellitus. In this work, an ultrafiltration liquid ...chromatography with quadrupole time‐of‐flight mass spectrometry method was proposed for the rapid identification of bioactive ingredients from Shenqi Jiangtang Granule using α‐glucosidase as an example. First, the chemical profile of this preparation was clarified, including 37 saponins, 17 flavonoids, 37 lignans, and seven other compounds. After incubation with α‐glucosidase in vitro, the methanol extract with an IC50 value of 0.19 mg/mL exhibited significant inhibitory activity. Then, 18 specific binding peaks were screened, and 15 peaks were identified. Among these, ten compounds were reported to have potential α‐glucosidase inhibitory activity for the first time. Subsequently, the inhibitory activities of these active compounds were evaluated by ultraviolet spectrophotometry with p‐nitrophenyl α‐d‐glucopyranoside as a substrate. As a result, gomisin J and gomisin D exhibited stronger α‐glucosidase inhibitory activities than other active compounds with IC50 values of 77.69 and 133.85 μM, respectively. The results demonstrated that the integrated ultrafiltration liquid chromatography with mass spectrometry method was an effective and powerful tool for the discovery of active ingredients in Shenqi Jiangtang Granule.
•UPLC-MS & NMR revealed 33 metabolite in two Hibiscus flower cultivars.•PCA and OPLS multivariate analyses were used to classify between cv.•Different Hibiscus tea preparations were assessed via ...q-NMR.•Compositional differences in Hibiscus tea preparations was characterized.•All Hibiscus tea preparations were effective α-glucosidase inhibitors.
Roselle (Hibiscus sabdariffa) is a functional food with potential health benefits, consumed either as hot or cold beverage. To ensure quality control of its various products, accurate measurement of active metabolites is warranted. Herein, we propose a combination of ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) and nuclear magnetic resonance (NMR) analytical platforms for the untargeted characterization of metabolites in two roselle cultivars, Aswan and Sudan-1. The analyses revealed 33 metabolites, including sugars, flavonoids, anthocyanins, phenolic and aliphatic organic acids. Their relative contents in cultivars were assessed via principle component analysis (PCA) and orthogonal projection to latent structures analysis (OPLS). Impact of the different extraction methods (decoction, infusion and maceration) was compared by quantitative 1H NMR spectroscopy, revealing cold maceration to be optimal for preserving anthocyanins, whereas infusion was more suited for recovering organic acids. The metabolite pattern revealed by the different extraction methods was found in good correlation for their ability to inhibit α-glucosidase enzyme.
•Callus was induced in Murashige-Skoog media from Piper longum leaf.•First report on antioxidant, antibacterial, and antidiabetic properties of callus.•Root dichloromethane fraction was more potent ...than others in all tested assays.•Callus was more potent than leaf and stem crude extracts in tested assays.•Antioxidant, antibacterial, and antidiabetic properties of extracts were correlated.
Piper longum L. is a tropical and subtropical medicinal plant that has been used as antidiabetic, diarrhea, stomachache, cough, asthma, and bronchitis since ancient times. The in vitro-grown callus from the leaf, however, has not been tested and utilized for any of these conditions. Thus, this research pursues to assess the comparative study of antioxidant, antibacterial, and antidiabetic activities of in vitro-grown callus and various parts of Piper longum-grown in the wild.
The antioxidant activity of crude extracts and the fractions were determined by DPPH (1,1-diphenyl-2-picrylhydrazyl) free-radical scavenging assay, the antibacterial activity by agar-well diffusion method, and antidiabetic activity by α-amylase and α-glucosidase inhibition assay. In addition, the total phenol content (TPC) and total flavonoid contents (TFC) were calculated using Folin-Ciocalteau reagent and aluminum chloride complex-forming assay respectively.
The highest antioxidant activity (IC50=134.81±1.16 µg/mL), TPC (41.22±0.50 mg of GAE/g dry weight), and TFC (73.41±0.53 mg of QE/g dry weight) were obtained in the dichloromethane (DCM) fraction of root than other crude extracts and fractions. The DCM fractions of root exhibited the minimum inhibitory concentration (MIC) at 5.0 mg/mL and minimum bactericidal concentration (MBC) of 8.35 mg/mL to the Staphylococcus aureus. Moreover, the DCM fraction of root showed the highest α-amylase and α-glucosidase inhibition (IC50=365.21±31.02 and 489.07±27.96 µg/mL) than other crude extracts and fractions. To the best of our information, comparative antioxidant (IC50=206.61±0.64 µg/mL), antibacterial (suppressed 80 % of tested bacteria), and antidiabetic (IC50=1165.15±15.63 and 1304.76±12.43 µg/mL) properties of the in vitro-grown callus were recorded for the first time in P. longum, and were found to be comparative to those of the wild-grown parts.
These results showed that wild-grown P. longum roots, particularly the DCM fraction, could be an important source of natural antioxidants, antimicrobials, and antidiabetics for better curative uses than other wild-grown parts and in vitro-grown callus. In vitro-grown callus, however, could be used as a natural drug source and used to conserve P. longum in its natural habitats in the future.
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Type-2 diabetes mellitus is one of the most prevalent metabolic diseases in the world, and is characterized by hyperglycemia (i.e., high levels of glucose in the blood). Alpha-glucosidases are ...enzymes in the digestive tract that hydrolyze carbohydrates into glucose. One strategy that has been developed to treat type-2 diabetes is inhibition of the activity of alpha-glucosidases using synthetic drugs. However, these inhibitors are usually associated with gastrointestinal side effects. Therefore, the development of inhibitors from natural products offers an alternative option for the control of hyperglycemia. In recent years, various studies have been conducted to identify alpha-glucosidases inhibitors from natural sources such as plants, and many candidates have transpired to be secondary metabolites including alkaloids, flavonoids, phenols, and terpenoids. In this review, we focus on the alpha-glucosidases inhibitors found in common vegetable crops and the major classes of phytochemicals responsible for the inhibitory activity, and also as potential/natural drug candidates for the treatment of type-2 diabetes mellitus. In addition, possible breeding strategies for production of improved vegetable crops with higher content of the inhibitors are also described.
The present study reports the new thiazole (A-L) derivatives based on benzothiazole fused triazole which were synthesized and assessed against thymidine phosphorylase and α-glucosidase enzymes. ...Several compounds with the same basic structure but different substituents were found to have high activity against the targeted enzymes, while others with the same basic skeleton but different substituents were found to have medium to low activity among the members of tested series. These analogs showed a varied range of inhibition in both case thymidine phosphorylase and alpha glucosidase, A (IC50 = 7.20 ± 0.30µM and IC50 = 1.30 ± 0.70µM), B (IC50 = 8.80 ± 0.10µM and IC50 = 2.10 ± 0.30µM), C (IC50 = 8.90 ± 0.40µM and IC50 = 3.20 ± 0.20µM) and thiazole containing analogs such as G (IC50 = 11.10 ± 0.20µM and IC50 = 7.80 ± 0.20µM) and H (IC50 = 12.30 ± 0.30µM and IC50 = 6.30 ± 0.20µM). When compared with standard drugs 7-Deazaxanthine, 7DX (IC50 = 10.60 ± 0.50µM) and acarbose (IC50 = 4.30 ± 0.30µM) respectively. These analogs were also subjected to molecular docking studies which indicated the binding interaction of molecules with active sites of the enzyme and strengthen the drug profile of these compounds. ADMET studies also predict the drug-like properties of these compounds, with no violations of drug likeness rules.
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•Synthesis and spectroscopic characterization of novel benzothiazole-triazole based thiazole derivatives.•Isolated compounds were evaluated for in vitro against thymidine phosphorylase and α-glucosidase.•A number of the compounds exhibited excellent activity, some better than the reference standards.•A molecular docking and ADMET study was used to determine the binding interactions of the potent compounds with the enzymes active sites and their toxicity respectively.•Exploration of better potentials via a series of studies.
Inhibition of DPP-4 enzyme actually increases the half life and biological activity of GLP-1 peptide as a result normal glucose level is achieved. Similarly, inhibition of α-glucosidase enzyme ...suppresses the cleavage of polysaccharides into glucose as a result normal blood glucose index is obtained for the management of diabetes. Sodium–glucose co-transporter 2 (SGLT2) actually reabsorbs the filtered glucose in the tubular nephron of the kidney and thus is the major co-transporter.
Fig.1. Mechanism of action and inhibition of DPP-4 enzyme, α-glucosidase and SGLT2.
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•This review article is based on the management of diabetes mellitus which is one of the most challenging diseases of the present time.•DPP-4 enzyme, α-glucosidase enzyme and SGLT2 are effective therapeutic targets for the management of diabetes mellitus.•The identification of promising inhibitors of DPP-4 enzyme, α-glucosidase enzyme and SGLT2 from the natural products are presented.•Structure-activity relationship (SAR) of various inhibitors is also discussed.
Diabetes mellitus is a chronic metabolic disorder which is rapidly spreading worldwide. It is characterized by persistent elevated blood glucose level above normal values (hyperglycemia) due to defect in either insulin secretion or in insulin action or both of them. Currently approved oral synthetic antidiabetic drugs such as biguanides, thiazolidinediones, sulfonylureas, and meglitinides have shown undesirable side effects. Therefore, newer approaches and targets for the management of diabetes mellitus are highly desirable. Dipeptidyl peptidase-4 enzyme, α-glucosidase enzyme and sodium-dependent glucose co-transporter 2 (SGLT2) have been recognized as effective therapeutic targets for the management of diabetes mellitus while natural products are alternatives to oral synthetic hypoglycemic agents. During the last two decades, many researchers were working on the identification and the validation of plant-derived products for curing various diseases. Natural products do not only provide useful drugs in their own right but also provide templates for the development of more effective compounds for enhanced therapeutic potential. Herein, we advocated the vital role of natural products as source of new drugs by presenting promising inhibitors of dipeptidyle peptidase-4 enzyme, α-glucosidase enzyme and (SGLT2) obtained from different medicinal plants as potential candidates for drug development against diabetes mellitus. The structure–activity relationship (SAR) of these various inhibitors is also discussed.
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A new series of Deacetylsarmentamide A and B derivatives, amides and sulfonamides of 3,4-dihydroxypyrrolidines as α-glucosidase inhibitors were designed and synthesized. The ...biological screening test against α-glucosidase showed that some of these compounds have the positive inhibitory activity against α-glucosidase. Saturated aliphatic amides were more potent than the olefinic amides. Among all the compounds, 5o/6o having polar –NH2 group, 10f/11f having polar –OH group on phenyl ring displayed 3–4-fold more potent than the standard drugs. Acarbose, Voglibose and Miglitol were used as standard references. The promising compounds 6i, 5o, 6o, 10a, 11a, 10f and 11f have been identified. Molecular docking simulations were done for compounds to identify important binding modes responsible for inhibition activity of α-glucosidase.
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