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Twelve years following gastric bypass surgery, a cachectic 69-year-old woman presented with both fasting and postprandial hypoglycaemia. Postprandial symptoms were relieved by dietary modification and acarbose, as is common in such cases. During a supervised fast, symptomatic hypoglycaemia occurred. Concurrent laboratory testing showed suppression of plasma insulin, c-peptide, proinsulin and insulin-like growth factor II. However, beta-hydroxybutyrate was also low, surprising given insulin deficiency. Elevated plasma free fatty acid (FFA) concentrations suggested that lipolysis was not impaired, making cachexia/malnutrition a less likely cause of hypoglycaemia. The apparent diagnosis was failure to counter-regulate—subsequent plasma carnitine measurements showed carnitine deficiency which presumably prevented FFA transport across mitochondrial membranes for ketogenesis. Repletion with high-dose oral carnitine supplements effected resolution of fasting hypoglycaemia.

Abstract. Background: to evaluate the effects of Vitamin D3 on glyco-metabolic control in type 2 diabetic patients with Vitamin D deficiency. Methods: one hundred and seventeen patients were randomized to placebo and 122 patients to Vitamin D3. We evaluated anthropometric parameters, glyco-metabolic control, and parathormone (PTH) value at baseline, after 3, and 6 months. Results: a significant reduction of fasting, and post-prandial glucose was recorded in Vitamin D3 group after 6 months. A significant HbA1c decrease was observed in Vitamin D3 (from 7.6% or 60 mmol/mol to 7.1% or 54 mmol) at 6 months compared to baseline, and to placebo (p

Diabetes mellitus (DM) is a metabolic disorder and a significant health problem all over the world. The current study elucidates the inhibitory potentials of the benzothiazine-pyrazole hybrid series against the α-Glucosidase enzyme. The molecular docking was employed to determine the binding affinity of synthetic compounds (ligands) with α-Glucosidase enzyme (receptor) active sites via the molecular operating environment (MOE). The molecular docking analysis revealed the best inhibitory interaction between certain synthetic compounds and the enzyme's active sites (α-Glucosidase). These compounds were further examined for drug-like properties, which necessarily validate the use of the compound as a drug. Then selected compounds were subjected to in vitro analysis to find the inhibitory potential with minimal dose. All compounds were docked into the active sites with the best binding pose and low rmsd values. The anti-diabetic analysis revealed that compound ST3 is more active against α-Glucosidase with IC50 values 5.8 µM as compared to acarbose which is 58.8 µM. The present study exhibited compound 2c has a high proficiency in lowering blood glucose levels compared to acarbose. This study strengthened the scope of designing/synthesizing these benzothiazine-pyrazole hybrid molecules as anti-diabetic drug molecules in the pharmaceutical industry.

Diabetes is a worldwide public health disease. Currently, the most effective way to treat diabetes is to mitigate postprandial hyperglycemia by inhibiting carbohydrate hydrolysis enzymes in the digestive system. Plant extracts are rich in bioactive compounds, which can be used in diabetes treatment. This study aims to evaluate the polyphenols content in ethanolic extracts of avocado fruit and leaves (Persea americana Mill.). Additionally, their antioxidant activity using DPPH, while the inhibition ability of α-amylase was examined by reacting different amounts of the extracts with amylase compared to acarbose as standard inhibitor. The active compounds were detected in the extracts by LC/MS. The obtained results showed that the leaf extract recorded a significant content of total phenolic compounds compared to the fruit extract (178.95 and 145.7 mg GAE /g dry weight, respectively). The total flavonoid values ​​ranged from 32.5 to 70.08 mg QE/g dry weight of fruit and leaves extracts, respectively. Twenty-six phytogenic compounds were detected in leaf and fruit extract by LC/MS. These compounds belong to fatty acids, sterols, triterpenes, phenolic acids, and flavonoids. The antioxidant activity of extracts is due to the exist of phytogenic compounds, i.e., polyphenols and flavonoids. The antioxidant activity increased in a concentration dependant manner. Avocado fruit extract (1000µg/mL) scavenged 95% of DPPḢ while leaf extract rummaged 91.03% of free radicals compared with Vit C and BHT. Additionally, higher α-amylase inhibitory activity was observed in fruit extract than the leaf extract, where the fruit and leaf extract (1000 μg/ml) inhibited the enzyme by 92.13% and 88.95%, respectively. The obtained results showed that the ethanolic extracts of avocado had a significant impact on human health due to their high content of polyphenols.

α-glucosidase is a primary carbohydrate digestive enzyme, present in the brush border of the small intestine that acts on the 1–4 associated α-glucose residues and could play an effective role in overall glycemic control. Berberis lycium and Fagonia cretica extracts are traditionally being used as antidiabetic. In the present study, ethanolic and methanolic extracts of B. lycium and F. cretica were tested against α-glucosidase. Furthermore, the isolated phytochemicals of these plants were screened computationally for the evaluation of active compounds. An in vitro assay, the Ethanol and methanol-based extracts of B. lycium and F. cretica for α-glucosidase inhibitory potential at a concentration range of 7.81–1000 µg/ml was used. The α-glucosidase inhibitory effect of extracts was compared based on their resulting IC50 values. The result showed that the extracts showed potent inhibitory activity against alpha-glucosidase. Methanolic extract of B. lycium with an IC50 value of 34.99 µg/ml was the most potentextract. The rest of the extracts showed moderate inhibitory activity with an IC50 value in the range of 48.17 µg/ml, to 66.53 µg/ml. The reported compounds were docked against α-glucosidase along with standard inhibitor (acarbose) to check the inhibitory potential of these compounds using computational tools. Among the 38 phytochemicals, phytic acid and sindamine showed remarkable interaction with α-glucosidase active site residues with docking score -20.0204 and -18.2239 respectively, while quercetin and palmatine-CHCl3 showed comparable docking score -14.7862 and -14.1882 respectively with the standard acarbose having docking score -15.5940 against α-glucosidase. We further validate our results in vitro by using. We concluded from the results that phytochemical extracted from medicinal plants show good potency and however in future in vivo studies are needed to cure diabetes mellitus.

Enzyme inhibitor from natural origin without any side effects and multi diseases target provide more advantageous over commercial drugs. In present study phytocompound lupeol was isolated from Indian traditional medicinal plant Crateva adansonii leave extracts and its possible applications for treating diabetes and inflammation diseases. Single major peak in HPLC profiling and FTIR functional group analysis of lupeol fraction (LF) confirmed the presence of phytocompound lupeol in LF. LF obtained from chloroform leave extract of Crateva adansonii had most prominent inhibitory activity on alpha-amylase and alpha glucosidase with IC50 values 16.31 µg/mL and 41.25 µg/mL respectively. LF exhibit superior COX-2 enzyme (91.36%) inhibition potential among all tested samples whereas LF exhibit equipotent (81.38%) MPO enzyme inhibitory potential compared with celecoxib standard drug (86.19%). In silico validation reveals that lupeol exhibit least docking score with excellent binding affinities of -9.2, -7.6, -10.0 -8.2 Kcal/mol with COX-2, myeloperoxidase, α-amylase and α-glucosidase inflammatory molecular target enzymes respectively than inflammatory (celecoxib) and diabetic (acarbose) reference standard drugs. Further in silico molecular dynamics simulation analysis revealed that Lupeol-COX-2 RMSD (root mean square deviation) plot showed that both COX-2 and Lupeol are stable after 20 NS at 9.0 A for ligand and 3.2 A for protein. Lupeol-α amylase complex showed good level of interaction throughout the simulation when compared with reference standard drug acarbose. Present study findings suggests that lupeol from Crateva adansonii plant could be incorporated in medicinal formulations intended for treatment of chronic inflammation and diabetic disorders.

The human microbiome encodes a large repertoire of biochemical enzymes and pathways, most of which remain uncharacterized. Here, using a metagenomics-based search strategy, we discovered that bacterial members of the human gut and oral microbiome encode enzymes that selectively phosphorylate a clinically used antidiabetic drug, acarbose1,2, resulting in its inactivation. Acarbose is an inhibitor of both human and bacterial α-glucosidases3, limiting the ability of the target organism to metabolize complex carbohydrates. Using biochemical assays, X-ray crystallography and metagenomic analyses, we show that microbiome-derived acarbose kinases are specific for acarbose, provide their harbouring organism with a protective advantage against the activity of acarbose, and are widespread in the microbiomes of western and non-western human populations. These results provide an example of widespread microbiome resistance to a non-antibiotic drug, and suggest that acarbose resistance has disseminated in the human microbiome as a defensive strategy against a potential endogenous producer of a closely related molecule. Bacteria in the human gut and oral microbiome encode enzymes that selectively phosphorylate the antidiabetic drug acarbose—an inhibitor of both human and bacterial α-glucosidases—resulting in its inactivation and limiting the drug's effects on the ability of the host to metabolize complex carbohydrates.

A phytochemical investigation of the rhizomes of Curcuma zedoaria was carried out, leading to the isolation of a new diphenylheptanoid, zedoaroxane A (1), together with four known compounds (2–5). Their structures were elucidated based on NMR spectroscopic data. All isolated compounds possessed α-glucosidase inhibitory activity, with the IC50 values ranging from 35.2 to 89.0 µM, more potent than that of the positive control acarbose (IC50, 214.5 µM).

A new xanthone glycoside, 1,8-dihydroxyl-2,5-dimethoxy-xanthone-6-O-β-D-glucoside (1), along with two known xanthone glycosides and two flavonoid glycosides were isolated from the aerial parts of Lomatogonium rotatum (L.) Fries es Nym. The structure of 1 was elucidated by analysis of its spectroscopic data, including UV, IR, HR-ESI-MS and extensive 1 D and 2 D NMR techniques. In vitro test, compound 1 behaved similarity to swertianolin against α‑glucosidase and more potent inhibitory effects than the positive control, acarbose.

Background: Infusate of the whole plant of Physalis angulata is used traditionally for the remedy of various diseases including diabetes and gout. This study focused on the stem of P. angulata . The objectives of this study were to investigate the potential of the stem infusate (INPA) and ethanol extract (EEPA) of P. angulata as inhibitors of α-glucosidase and xanthine oxidase. Materials and Methods: INPA and EEPA were determined for their α-glucosidase and xanthine oxidase inhibition activities in vitro , whereas antioxidant activity was determined by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assay. Reference inhibitors were used for comparison. The total phenolic compounds were also estimated. Results: EEPA had more concentrated phenolic than INPA which were 7.96 and 0.08 mgGAE/g dried biomass, respectively. INPA and EEPA inhibited α-glucosidase considerably, with IC50 of 149.11 and 409.86 µg/mL, respectively (acarbose was 130.66 µg/mL). However, they inhibited xanthine oxidase weakly, with IC50 of 0.546 and 2.643 mg/mL, respectively, compared with allopurinol 0.005 mg/mL. EEPA scavenged DPPH radicals very weakly (16.04 mg/mL) compared to BHT (0.021 mg/mL), whereas no activity was observed for INPA. Conclusion: The stem infusate and ethanol extract of P. angulata are able to inhibit the activity of α-glucosidase, thus can be further explored for sources of bioactive compounds with α-glucosidase inhibition activity. Keywords: α-glucosidase, infusate, ethanol extract, Physalis angulata , stem, xanthine oxidase

In this study, we have investigated a series of indole-based compounds for their inhibitory study against pancreatic α-amylase and intestinal α-glucosidase activity. Inhibitors of carbohydrate degrading enzymes appear to have an essential role as antidiabetic drugs. All analogous exhibited good to moderate α-amylase (IC50 = 3.80 to 47.50 μM), and α-glucosidase inhibitory interactions (IC50 = 3.10–52.20 μM) in comparison with standard acarbose (IC50 = 12.28 μM and 11.29 μM). The analogues 4, 11, 12, 15, 14 and 17 had good activity potential both for enzymes inhibitory interactions. Structure activity relationships were deliberated to propose the influence of substituents on the inhibitory potential of analogues. Docking studies revealed the interaction of more potential analogues and enzyme active site. Further, we studied their kinetic study of most active compounds showed that compounds 15, 14, 12, 17 and 11 are competitive for α-amylase and non- competitive for α-glucosidase.

Lulu Song,1 Xiaomu Kong,2 Zhaojun Yang,1 Jinping Zhang,1 Wenying Yang,1 Bo Zhang,1 Xiaoping Chen,1 Xin Wang1 1Department of Endocrinology, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 2Clinical Laboratory, China-Japan Friendship Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xin WangDepartment of Endocrinology, China-Japan Friendship Hospital, 2 Yinghua East Road, Beijing, 100029, People’s Republic of ChinaTel +86 1084205254Email xiangpian11@163.comPurpose: To assess the effect of acarbose in lowering low-grade albuminuria compared to metformin in newly diagnosed Chinese type 2 diabetes (T2DM) patients.Patients and Methods: The Metformin and AcaRbose Clinical Trial was a randomized, open-label trial in newly diagnosed T2DM patients. Participants received 48 weeks of monotherapy with acarbose (100 mg three times a day) or metformin (1500 mg once a day). As the hypoglycemic effect of acarbose and metformin has been evaluated in previous reports. This analysis studied the effect of the two antidiabetic drugs on reducing urinary albumin. The percent change in the urinary albumin/creatinine ratio (uACR) from baseline to week 48 was analyzed, and ANCOVA was employed to establish whether the effect in decreasing uACR was mediated by metabolic improvement.Results: Acarbose reduced the adjusted mean percent uACR by − 31.5% (95% confidence interval [CI] − 48.4 to − 7.5) compared with metformin. When adjusting for changes in glycated hemoglobin, body weight, systolic blood pressure and triglycerides or changes in area under the curve of glucagon-like peptide 1 (AUCGLP-1) in the standard meal test, the uACR-lowering effect was not attenuated. If stratified by eGFR, blood glucose level, sex or uACR level, the effect of acarbose versus metformin was consistent across subgroups. The proportion of patients with a reduction in uACR of at least 70% was 48.6% in the acarbose group and 34.1% in the metformin group.Conclusion: Acarbose lowered the uACR compared to metformin in newly diagnosed T2DM patients independent of improvements in hyperglycemia, blood pressure, body weight and triglycerides.Keywords: diabetes mellitus, type 2, diabetic nephropathies, hypoglycemic agents

Objective Polycystic ovary syndrome (PCOS) is a complex endocrine condition affecting women of reproductive age. It is characterized by insulin resistance and is a major risk factor for type 2 diabetes mellitus (T2DM). The objective was to review the literature on the effect of different pharmacological interventions on insulin resistance in women with PCOS. Design We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library and the Web of Science in April 2020 and updated in March 2021. The study follows the 2020 Preferred Reporting Items for Systematic reviews and Meta-ana. Reviwers extracted data and assessed the risk of bias using the Cochrane risk of bias tool. Results In 58 randomized controlled trials there were significant reductions in the fasting blood glucose (FBG) with metformin versus placebo (standardized mean difference [SMD]: -0.23; 95% confidence interval [CI]: -0.40, -0.06; I² = 0%, low-grade evidence), and acarbose versus metformin (mean difference [MD]: -10.50 mg/dl; 95% CI: -15.76, -5.24; I² = 0%, low-grade evidence). Significant reductions in fasting insulin (FI) with pioglitazone versus placebo (SMD: -0.55; 95% CI: -1.03, -0.07; I² = 37%; p = .02, very-low-grade evidence). A significant reduction in homoeostatic model assessment of insulin resistance (HOMA-IR) was seen with exenatide versus metformin (MD: -0.34; 95% CI: -0.65, -0.03; I² = 0%, low-grade evidence). No effect on homoeostatic model assessment of beta cells (HOMA-B) was observed. Conclusions Pharmacological interventions, including metformin, acarbose, pioglitazone and exenatide have significant effects on FBG, FI, HOMA-IR but not on HOMA-B.

A green and efficient one-pot multi-component protocol was developed for the synthesis of some novel dihydrochromeno[4,3-b]pyrrol-3-yl derivatives through the reaction of arylglyoxals, malono derivatives, and different 4-amino coumarins in ethanol at reflux condition. In this method, all products were obtained in good to excellent yield. Next, all synthesized derivatives were evaluated for their α-glucosidase inhibitory activity. Most of the compounds displayed potent inhibitory activities with IC50 values in the range of 48.65 ± 0.01–733.83 ± 0.10 μM compared to the standard inhibitor acarbose (IC50 = 750.90 ± 0.14 μM). The kinetic study of compound 5e as the most potent derivative (IC50 = 48.65 ± 0.01 μM) showed a competitive mechanism with a Ki value of 42.6 µM. Moreover, docking studies revealed that dihydrochromeno[4,3-b]pyrrol-3-yl effectively interacted with important residues in the active site of α-glucosidase. Supplementary Information The online version contains supplementary material available at 10.1007/s11030-021-10337-w.

The effective synthesis of benzoconduritols C and D is reported. Oxidation of oxabenzonorbornadiene followed by acetylation with Ac2O/pyridine or AcCl/CH2Cl2 gave the corresponding exo-diacetate compound stereoselectively. Acid-catalyzed ring opening of the bridged ether bond (the 1,4-anhydo bond) with Ac2O in the oxabenzonorbornadiene system to produce benzoconduritol tetraacetates followed by ammonolysis furnished the desired benzoconduritols C and D, respectively. The novel benzoconduritols (9, 10, 15, 16, and 17) were evaluated for the first time in terms of their potential antioxidant, anti-inflammatory, and enzyme inhibition activities. Most of the complexes exhibited moderate activity. Especially 15 (IC50 = 0.374 mM) and 10 (IC50 = 0.450 mM) have better anti-inflammatory effect when compared to ibuprofen (IC50 = 0.437 mM). Furthermore, the benzoconduritol C 9 has better α-glucosidase inhibition potential with the IC50 value of 0.437 mM than acarbose (IC50 = 0.445 mM). The results of this study point out that most of these molecules have the potential to provide an alternative for the clinical control of inflammation and diabetes due to their anti-inflammatory and anti-glucosidase activities.

A series of phosphorylated derivatives of purine were synthesized in good yields (88–95%) by the reaction of 2‐chloro‐4‐{[(9H‐purin‐9‐yl)methoxy]methyl}‐1,3,2-λ5‐dioxaphospholan‐2‐one with various ...

Yacon (Smallanthus sonchifolius (Poepp.) H. Robinson) leaves is traditionally consumed as herbal tea in many countries including Indonesia. This plant's antidiabetic properties have been extensively researched, but studies on the responsible active compound identification are scarce. Information on the active compounds is critical for the consistency of Yacon herbal tea quality. The aim of this study was to identify α-glucosidase inhibitors in Indonesian Yacon leaves grown in two different locations using FTIR- and LC-MS/MS-based metabolomics in combination with in silico technique. Yacon leaves ethanol (50 and 95%) and water extracts were tested for α-glucosidase inhibitory activity, with the 95% ethanol extract being the most active. Geographical origins were found to have no major impact on the activity. In parallel, chemical profile of Yacon leaves extract was determined using FTIR and LC-MS/MS. Orthogonal Projection to Latent Structure (OPLS) was used to analyze both sets of data. OPLS analysis of FTIR data showed that compounds associated to α-glucosidase inhibitor activity included those with functional groups -OH, stretched CH, carbonyl, and alkene. It was consistent with the result of OPLS analysis of LC-MS/MS data, which revealed that based on their VIP and Y-related coefficient value, nystose, 1-kestose, luteolin-3'-7-di-O-glucoside, and 1,3-O-dicaffeoilquinic acid isomers, strongly linked to Yacon's α-glucosidase inhibitor activity. In silico study supported these findings, revealing that the four compounds were potent α-glucosidase inhibitors with docking score in the range of - 100.216 to - 115.657 kcal/mol, which are similar to acarbose (- 115.774 kcal/mol) as a reference drug.

Elaeagnus rhamnoides (L.) A. Nelson (synonym: Hippophae rhamnoides) (Elaeagnaceae) is an important plant with multiple usages. The current study was laid on discovering the phytochemical profiling of E. rhamnoides leaves through antihyperglycemic and antioxidant effects. The ethyl acetate (IC50 = 46.89 ± 2.18 µg/mL) and n-butanol extracts (IC50 = 51.33 ± 2.53 µg/mL) possessed potent inhibitory activity against α-glucosidase enzyme as compared with standard compound, acarbose (IC50 = 4212.62 ± 130.00 µg/mL). Seven compounds were isolated, and their structure was determined by 1D- and 2D-NMR. Isorhamnetin-3-O-β-d-glucopyranosyl-7-O-α-l-rhamnopyranoside (1), isorhamnetin-7-O-α-l-rhamnopyranoside (2), isoquercitrin (3), narcissin (4), isorhamnetin-3-O-β-d-glucopyranoside (5), arjunglucoside I (6), and casuarinin (7) were isolated from n-butanol extract. All isolated compounds, especially arjunglucoside I (IC50 = 1074 ± 32 µM) and casuarinin (IC50 = 21 ± 2 µM), showed higher α-glucosidase inhibitory activity than acarbose (IC50 = 6561 ± 207 µM). Casuarinin displayed powerful scavenging activity against to both ABTS radical with 2 ± 1 µM IC50 value and DPPH radical with 14 ± 1 µM IC50 value while IC50 values of trolox and α-tocopherol were 31 ± 1 and 50 ± 1 µM against ABTS radical, and 67 ± 2 and 95 ± 3 µM against DPPH radical, respectively. Arjunglucoside I was isolated for first time from this species and Elaeagnaceae family. Preparations prepared from E. rhamnoides leaf extracts standardized via casuarinin and arjunglucoside I could be potential phytotherapeutics for diabetes mellitus.

Objective: To screen for α-glucosidase inhibitor active compounds in the total saponins of Baibiandou (Lablab Semen Album) based on UHPLC-Q-Exactive Orbitrap MS technology and to evaluate its hypoglycemic activity in vivo. Methods: Acarbose was used as the positive control, and the median inhibitory concentration (IC50) was used as the evaluation index of α-glucosidase inhibitory activity to establish an in vitro α-glucosidase inhibition model. Further, UHPLC-Q-Exactive Orbitrap MS technology was used to screen and identify the active compounds of α-glucosidase inhibitors in the total saponins of Baibiandou (Lablab Semen Album) in order to further verify the activity of the main active monomer and to perform homologous modeling and molecular docking of yeast-derived α-glucosidase and human-derived α-glucosidase, while the hypoglycemic activity was evaluated in diabetic mice. Results: This study successfully identified 15 compounds with potential α-glucosidase inhibitory activity, including Chikusetsusaponin IVa, from the total saponins of Baibiandou (Lablab Semen Album). Simultaneously, we verified the activity of the main active monomer Chikusetsusaponin IVa, and showed that it has strong α-glucosidase inhibitory activity. The α-glucosidase inhibitory concentration IC50 was (565.2 ± 1.026) μg/mL, and the IC50 of acarbose, which was lower than the positive control, was (706.6 ± 1.058) μg/mL. The docking energies of Chikusetsusaponin IVa were – 6.1 and – 7.7 kcal/mol with yeast-derived α-glucosidase and human-derived α-glucosidase molecules, respectively. Both showed strong binding activity, and the levels of alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), UREA, Creatinine (CREA), and cholesterol (CHO) were significantly decreased by Chikusetsusaponin IVa (P < 0.05). In addition, it could repair damaged liver and pancreas cells of diabetic mice to some extent. Conclusion: This study provides a basis for screening α-glucosidase inhibitors and structural modifications of the total saponins of Baibiandou (Lablab Semen Album).

Постпрандіальний гіпоглікемічний синдром, або реактивна гіпоглікемія, — вегетативні симптоми, такі як слабкість, втома, голод, нудота, серцебиття, занепокоєння, тремор, пітливість, що виникають через одну-дві години після прийому їжі. Синдром досить слабо висвітлений у літературі, більшість відомостей є розрізненими. Лабораторні критерії діагностики постпрандіальної реактивної гіпоглікемії досить контроверсивні, але більшість авторів схиляються до того, що це рівень глюкози крові нижче тощакової або ≤ 3,9 ммоль/л протягом двох годин після прийому їжі. Гіпоглікемія є результатом дисбалансу між надходженням глюкози в кров (від ендогенної продукції глюкози або екзогенної доставки) і використанням глюкози тканинами. Баланс між надходженням і витрачанням глюкози контролюється складною рівновагою глікорегулюючих гормонів. Інсулін, глюкагон і адреналін діють протягом кількох хвилин, а кортизол і гормон зросту — кілька годин. Це пояснює наявність негайних і відстрочених різноманітних ефектів: адренергічного, нейроглікопенічного, гастроінтестинального дискомфорту. Відомо, що в генезі постпрандіального синдрому лежать механізми, подібні до постгастректомічних у пацієнтів, оперованих з приводу морбідного ожиріння. Найбільш імовірним чинником формування реактивної гіпоглікемії є постпрандіальна гіперсекреція інсуліну під впливом глюкози і глюкагоноподібного пептиду (GLP-1), що є компонентом ентероендокринної системи, основна дія якого спрямована на цефалічну фазу формування насичення. Як у оперованих пацієнтів, так і у відносно здорових осіб симптоми виникають після прийому їжі, багатої простими вуглеводами. Симптоми досить ефективно лікуються прийомом їжі з вживанням вуглеводів із низьким глікемічним індексом і харчовими волокнами. При недостатності ефекту використовують препарати акарбози, інгібуючої α-глюкозидази тонкого кишечника, що є основним стимулом для секреції GLP-1. Таким чином, при епідемічній швидкості поширення ожиріння в умовах неадекватних харчових пріоритетів у дитячій популяції ймовірність значної поширеності постпрандіального синдрому досить вірогідна, що вимагає додаткового дослідження. При цьому зниження в раціоні простих вуглеводів може істотно поліпшити якість життя дітей із постпрандіальним дискомфортом.

Response surface methodology was utilized to optimize the microwave-assisted extraction of flavonoids from Eucommia ulmoides Oliver seed meal. In addition, the optimal processing conditions for the extraction of E. ulmoides seed meal flavonoids were as follows: a processing time of 30 min, a liquid to solid ratio of 54 to 1 (mL/g), an ethanol concentration of 77%, and a temperature of 69 °C. The total flavonoids extraction percentage was 0.6611%. Moreover, the total flavonoids extracted from E. ulmoides seed meal were good for scavenging diphenyl picryl hydrazinyl. The E. ulmoides seed meal total flavonoids exhibited an obvious dose-dependent inhibitory effect on α-glucosidase in the concentration range of 0.05 to 1.0 mg·mL−1. The IC50 value of the E. ulmoides seed meal flavonoids was slightly lower than the IC50 value of acarbose. According to the results of the xanthine oxidase inhibitory activity test, the IC50 value of the E. ulmoides seed meal flavonoids was higher than the IC50 value of allopurinol.

A novel series of phenoxymethybenzoimidazole derivatives (9a-n) were rationally designed, synthesized, and evaluated for their α-glycosidase inhibitory activity. All tested compounds displayed promising α-glycosidase inhibitory potential with IC50 values in the range of 6.31 to 49.89 μM compared to standard drug acarbose (IC50 = 750.0 ± 10.0 μM). Enzyme kinetic studies on 9c, 9g, and 9m as the most potent compounds revealed that these compounds were uncompetitive inhibitors into α-glycosidase. Docking studies confirmed the important role of benzoimidazole and triazole rings of the synthesized compounds to fit properly into the α-glycosidase active site. This study showed that this scaffold can be considered as a highly potent α-glycosidase inhibitor. Supplementary Information The online version contains supplementary material available at 10.1007/s11030-021-10310-7.

Background: The inhibition of α-amylase enzyme is one of the best therapeutic approach for the management of type II diabetes mellitus. Chalcone possesses a wide range of biological activities. Objective: In the current study chalcone derivatives (1-16) were synthesized and evaluated their inhibitory potential against α-amylase enzyme. Methods: For that purpose, a library of substituted (E)-1-(naphthalene-2-yl)-3-phenylprop-2-en-1-ones was synthesized by Claisen-Schmidt condensation reaction of 2-acetonaphthanone and substituted aryl benzaldehyde in the presence of base and characterized via different spectroscopic techniques such as EI-MS, HRESI-MS, 1H-, and 13C-NMR. Results: Sixteen synthetic chalcones were evaluated for in vitro porcine pancreatic α-amylase inhibition. All the chalcones demonstrated good inhibitory activities in the range of IC50 = 1.25 ± 1.05 to 2.40 ± 0.09 μM as compared to the standard commercial drug acarbose (IC50 = 1.34 ± 0.3 μM). Conclusion: Chalcone derivatives (1-16) were synthesized, characterized, and evaluated for their α- amylase inhibition. SAR revealed that electron donating groups in the phenyl ring have more influence on enzyme inhibition. However, to insight the participation of different substituents in the chalcones on the binding interactions with the α-amylase enzyme, in silico (computer simulation) molecular modeling analyses were carried out.

Sixteen compounds (1-16) were isolated from Impatiens chapaensis. Chemical structures were determined by spectroscopic analyses and comparisons with previously published data. This report is the first to identify compounds 1, 5–7, 10, 12–14, and 16 from the genus Impatiens. Seven chosen isolates (5, 7, 10, 11, 12, 15, and 16) were submitted for α-glucosidase inhibition assays with acarbose as the positive control (IC50 = 227.14 ± 13.71 µM). Flavonoid 5 exhibited a significant inhibitory effect (IC50 = 101.00 ± 9.01 µM).

The purpose of this research was to determine the α-glucosidase enzyme inhibitory activity of Moringa oleifera plant samples collected from the three geographical areas viz., Saragi, Bacuhau, and Batumatongka of Southeast Sulawesi Indonesia. Ethanol extract of Moringa leaves was prepared by the maceration method using 95% ethanol. The estimation of α –glucosidase inhibitory activity of this extract was performed in vitro. The results of the study showed that ethanolic extract of three Moringa samples i.e. Sarangi, Bacuhau, and Batumatongka had the IC50value of 18.62, 10.18, 10.58 ppm, respectively while IC50value for the acarbose positive control was reported 11.54ppm. From the results of this study, it can be concluded that ethanolic extract of Moringa could inhibit α –glucosidase and this potential was similar to the commercial α –glucosidase inhibitor acarbose.

Diabetes Mellitus is a global health problem that leads to various complications associated with hyperglycemia.In traditional medicine, herbal treatment is one of the alternative ways to cope with this type of disease. Theaim of this study is to investigate the antidiabetic and hepato-pancreatic protective effects of the mixture ofPrunus spinosa leaves and flowers (PSE) extract in streptozocin-induced diabetes mellitus. Seven randomexperimental groups of Wistar rats (n = 8) were created as followed; control, diabetic, PSE25, PSE50, insulin,metformin, and acarbose. a-amylase and a-glucosidase inhibitory activities of PSE were determined. Antioxidantenzymes activities and lipid peroxidation were analyzed in the liver tissue. Histopathological examinationof liver and pancreas was also performed. a-amylase and a-glucosidase IC50 inhibition values of PSE werefound more efficient, comparing to those of standard acarbose. While blood glucose levels severely increasedin all diabetic groups, PSE25 and PSE50 treatments were effective in regulating blood glucose levels. Moreover,administration of PSE25 and PSE50 improved insulin levels compared to the diabetic group. Although increasedoxidative stress in the diabetes seriously suppressed antioxidant activities, PSE25 and PSE50 supplementationsignificantly recuperated liver antioxidant capacity. Despite severe degenerative and necrotic changes in diabetes,these findings alleviated with PSE administrations. Moreover, PSE treatments remarkably recuperatedb-cells. These results reveal that there may be an alternative way to control high blood glucose levels, which isone of the most important complications of diabetes. Furthermore, PSE can provide a protection against oxidativestress, liver and pancreatic damage by augmenting antioxidant capacity in diabetes.

Purpose In the Guidelines for the Prevention and Control of Type 2 Diabetes in China (2017 edition), intensive lifestyle interventions are recommended for preventing the progression of impaired glucose tolerance (IGT) to type 2 diabetes mellitus. Acarbose and metformin can also be considered if intensive lifestyle modification has been ineffective for 6 months. But the effects of intensive lifestyle modification and glucose-lowering drug interventions that work best in the population with IGT are unclear. This network meta-analysis assessed the effectiveness of intensive lifestyle modification, acarbose, and metformin in treating populations with IGT. Methods We systematically searched both Chinese- and English-language databases, including China Knowledge, the Cochrane Library, Embase, PubMed, VIP, and Wanfang, for articles published between database inception and September 2019. Randomized, controlled clinical trials in patients with IGT treated with acarbose, metformin, and intensive lifestyle modification were assessed for eligibility. The data from all included studies were evaluated by 2 reviewers independently in accordance with the Cochrane Handbook for Systematic Reviews of Intervention version 6.0. A network meta-analysis was performed by using R software version 3.6.1. Findings The data from 53 randomized controlled trials were included in the review, with a sample size of 21,208 patients. Compared with the control group, the use of acarbose, metformin, and/or intensive lifestyle modification was associated with reduced rates of progression to diabetes (relative risks [RRs] [95% credible intervals]: acarbose, 0.37 [0.29–0.47]; metformin, 0.39 [0.30–0.50]; intensive lifestyle modification, 0.61 [0.50–0.73]). The surface under the cumulative ranking (SUCRA) value of acarbose was 88.35%, supporting that acarbose was more effective in reducing the rate of progression to diabetes compared with controls. With acarbose, metformin, and intensive lifestyle modification, the rates of achieving a normal glucose level were increased by RR = 2.1, 1.7, and 1.2, respectively when compared with control group. The SUCRA value of acarbose was 99.69%, supporting the optimal effect of acarbose in achieving a normal blood glucose level. Implications In this meta-analysis in patients with IGT, compared with controls, acarbose and metformin were associated with decreased rates of progression to diabetes and increased rates of achieving a normal glucose level. Acarbose use was associated with an increased rate of achieving a normal glucose level, while intensive lifestyle modification was not.

Diabetes mellitus is a disease of endocrine and metabolism disorders, characterized by hyperglycemia, and increased risk of cardiovascular disease complications. Although oral hypoglycemic drugs have the effect of maintaining blood sugar control in diabetic patients, these drugs still have serious side effects for many patients, such as gastrointestinal diseases related to acarbose. Recently, certain food supplements and their bioactive ingredients have been shown to improve diabetes mellitus and can be readily found in the marketplace. This literature review focuses on food supplements with a hypoglycemic function, with an emphasis on their biologically active ingredients and pharmacological effects. The biologically active ingredients can be divided into 6 categories: polyphenols, polysaccharides, terpenoids, saponins, alkaloids, and others. The sources, models used for their study, efficacy, and mechanisms of action of food supplements are described. The sources, models used for their study, efficacy, and mechanisms of action of food supplements are described, including regulation of microflora, modulation of glucose metabolism, and improvement in insulin function. By classifying medicinal plants that can be used as food supplements and their activities, we have provided useful information to support further investigation and application of food supplements to prevent or improve diabetes mellitus.

Benzimidazole scaffolds are known to have a diverse range of biological activities and found to be antidiabetic and antioxidant. In this study, a variety of arylated benzimidazoles 1–31 were synthesized. Except for compounds 1, 6, 7, and 8, all are new derivatives. All compounds were screened for α-amylase inhibitory, 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities. In vitro screening results revealed that all molecules demonstrated significant α-amylase inhibition with IC50 values of 1.86 ± 0.08 to 3.16 ± 0.31 μM as compared to standard acarbose (IC50 = 1.46 ± 0.26 μM). However, compounds showed significant ABTS and DPPH radical scavenging potentials with IC50 values in the range of 1.37 ± 0.21 to 4.00 ± 0.10 μM for ABTS and 1.36 ± 0.09 to 3.60 ± 0.20 μM for DPPH radical scavenging activities when compared to ascorbic acid with IC50 values of 0.72 ± 0.21 and 0.73 ± 0.05 μM for ABTS and DPPH radical scavenging potentials, respectively. Structure–activity relationship (SAR) was established after critical analysis of varying substitution effects on α-amylase inhibitory and radical scavenging (ABTS and DPPH) potentials. However, molecular docking was also performed to figure out the active participation of different groups of synthetic molecules during binding with the active pocket of the α-amylase enzyme.

Benzoxazolyl linked meta- and para-substituted new chemical entities (5a–5h) featuring thiazolidinedione, rhodanine, hydantoin, and thiohydantoin moieties were synthesized and characterized by 1H NMR, 13C NMR, FT-IR, and HRMS spectral studies. In addition, all compounds were screened for α-glucosidase inhibitory activity and further supported by molecular docking studies carried out at the active site of α-glucosidase (PDB code: 3TOP) in comparison to acarbose used as a standard drug. Out of eight tested compounds, 5d was found as the most active inhibitor of α-glucosidase (IC50 = 9.48 ± 0.36 µM), having rhodanine moiety substituted at meta-position of the phenyl ring.

Prediabetes is a prevalent metabolic disorder with multiple complications, including nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the combinatorial effect of baicalein, a dietary flavonoid abundant in multiple edible plants, and acarbose on prediabetes-associated NAFLD. Baicalein and its metabolites inhibited de novo lipogenesis (DNL), thereby decreasing lipid accumulation and hepatokine secretion in oleic acid-induced hepatocytes. Carbohydrate restriction, which mimicked the effect of acarbose, led to comparable results. The combinatorial effect of baicalein and acarbose was further verified in prediabetic mice with NAFLD. Through the 16-week intervention, baicalein and acarbose inhibited DNL and improved glucose tolerance, oxidative stress, liver histology, and hepatokine secretion, thereby ameliorating insulin resistance and NAFLD. Our study demonstrated that baicalein enhanced the effect of acarbose on improving NAFLD and explored the underlying multitarget mechanism, laying a theoretical foundation for the development of flavonoid dietary supplements for the simultaneous improvement of NAFLD and prediabetes.

The current outbreak of COVID-19 is leading an unprecedented scientific effort focusing on targeting SARS-CoV-2 proteins critical for its viral replication. Herein, we performed high-throughput virtual screening of more than eleven thousand FDA-approved drugs using backpropagation-based artificial neural networks (q2LOO = 0.60, r2 = 0.80 and r2pred = 0.91), partial-least-square (PLS) regression (q2LOO = 0.83, r2 = 0.62 and r2pred = 0.70) and sequential minimal optimization (SMO) regression (q2LOO = 0.70, r2 = 0.80 and r2pred = 0.89). We simulated the stability of Acarbose-derived hexasaccharide, Naratriptan, Peramivir, Dihydrostreptomycin, Enviomycin, Rolitetracycline, Viomycin, Angiotensin II, Angiotensin 1-7, Angiotensinamide, Fenoterol, Zanamivir, Laninamivir and Laninamivir octanoate with 3CLpro by 100 ns and calculated binding free energy using molecular mechanics combined with Poisson-Boltzmann surface area (MM-PBSA). Our QSAR models and molecular dynamics data suggest that seven repurposed-drug candidates such as Acarbose-derived Hexasaccharide, Angiotensinamide, Dihydrostreptomycin, Enviomycin, Fenoterol, Naratriptan and Viomycin are potential SARS-CoV-2 main protease inhibitors. In addition, our QSAR models and molecular dynamics simulations revealed that His41, Asn142, Cys145, Glu166 and Gln189 are potential pharmacophoric centers for 3CLpro inhibitors. Glu166 is a potential pharmacophore for drug design and inhibitors that interact with this residue may be critical to avoid dimerization of 3CLpro. Our results will contribute to future investigations of novel chemical scaffolds and the discovery of novel hits in high-throughput screening as potential anti-SARS-CoV-2 properties.Communicated by Ramaswamy H. Sarma.

Although traditional practitioners prescribe Malewana Madhumeha Choorna hot infusion (MMCHI) in Sri Lanka to combat diabetes, its antidiabetic properties have yet to be explored. We examined the in vitro hypoglycemic activity of MMCHI using α-amylase, α-glucosidase enzymes, and glucose uptake assays. Further, in vitro antioxidant activity was determined using DPPH (2,2 diphenyl-1-picrylhdrazyl) and H2O2 free radical scavenging activities. To identify the phytochemicals present in the hot infusion, we conducted solvent-solvent fractionation (hexane, chloroform, ethyl acetate, methanol) procedures and subjected them to gas chromatography-mass spectrometry (GC-MS). Both MMCHI and fractions exhibited a dose-dependent inhibition of glucose uptake and the enzymes α-amylase and α-glucosidase. The hot infusion exhibited enzyme inhibitory activities more or less similar to the standard drug acarbose. Enzyme inhibition was especially pronounced with α-amylase. Glucose uptake by MMCHI was more potent than that of the standard drug, especially at the 125 µg/mL dose. Strong antioxidant scavenging activity, comparable to that of the standard drug, was observed in the MMCHI, further indicating its antidiabetic potential. The presence of organic compounds and essential oils in the extract was responsible for potent antidiabetic activities via inhibition of α-amylase enzyme. Also, MMICH exhibited strong free radical scavenging abilities. The current study justifies the use of MMCHI to manage diabetes.

Two new compounds, dendronobilate (1) and 4-O-demethyl-nobilone (2), together with one known fluorenone were isolated from the aerial parts of Dendrobium nobile Lindl. Their structures were characterized by detailed analysis of 1D and 2D NMR spectra, HRESIMS and ECD spectra. Compounds 1–3 showed significant α-glucosidase inhibitory activity with IC50 values of 27.46 ± 3.14, 4.52 ± 0.33, and 10.78 ± 2.05 μM, respectively, which were superior to the acarbose (745.9 ± 3.3 μM). The binding interactions of 1 and 2 with α-glucosidase were investigated using molecular docking simulations. In addition, compound 2 exhibited potent inhibitory effect on NO production in LPS activated RAW264.7 cells with the IC50 value of 35.40 ± 1.77 μM without cytotoxicity observed.

Santolina chamaecyparissus is an important medicinal plant growing in the Mediterranean region and has been reported as a potent anti-inflammatory, antibacterial, antioxidant, and antifungal agent. The purpose of the current research is to identify the chemical constituents in ethyl acetate extract (EAE) from the leaves of S. chamaecyparissus, and to evaluate antidiabetic, and anticancer activity. Chemical constituents of EAE were identified by GC-MS, and the antidiabetic activity was evaluated by α-glucosidase inhibition assay. The anticancer activity was assessed by Epidermal Growth Factor Receptor (EGFR) expression in human breast cancer cell line (MCF7) by using quantitative RT-PCR method. GC-MS analysis of EAE of S. chamaecyparissus yielded 44 compounds. Tetrapentacontane (27.15%), eicosyl acetate (8.40%), 2-methylhexacosane (6.87%), and n-pentadecanol (5.44%) were found as major chemical constituents. The EAE of S. chamaecyparissus showed concentration dependant inhibition of α-glucosidase enzyme and the IC50 value (IC50 110 ± 4.25 µg/mL) was found comparable with standard acarbose (IC50 105 ± 3.74 µg/mL). The real-time qRT-PCR results showed that the EGFR protein (bcl-2) in human breast cancer cell line (MCF7) was negatively expressed with a value of −0.69297105 after treatment with EAE (100 µg/mL). The study results are suggesting the possible use of S. chamaecyparissus in the management of diabetes, and human breast cancer.

α-Glucosidase (EC 3.2.1.20) is a carbohydrate-hydrolyzing enzyme which generally cleaves α-1,4-glycosidic bonds of oligosaccharides and starch from the nonreducing ends. In this study, the novel α-glucosidase from Weissella cibaria BBK-1 (WcAG) was biochemically and structurally characterized. WcAG belongs to glycoside hydrolase family 13 (GH13) and to the neopullanase subfamily. It exhibits distinct hydrolytic activity towards the α-1,4 linkages of short-chain oligosaccharides from the reducing end. The enzyme prefers to hydrolyse maltotriose and acarbose, while it cannot hydrolyse cyclic oligosaccharides and polysaccharides. In addition, WcAG can cleave pullulan hydrolysates and strongly exhibits transglycosylation activity in the presence of maltose. Size-exclusion chromatography and X-ray crystal structures revealed that WcAG forms a homodimer in which the N-terminal domain of one monomer is orientated in proximity to the catalytic domain of another, creating the substrate-binding groove. Crystal structures of WcAG in complexes with maltose, maltotriose and acarbose revealed a remarkable enzyme active site with accessible +2, +1 and −1 subsites, along with an Arg–Glu gate (Arg176–Glu296) in front of the active site. The −2 and −3 subsites were blocked by Met119 and Asn120 from the N-terminal domain of a different subunit, resulting in an extremely restricted substrate preference.

Introduction: Sambiloto (Andrographis paniculata) is an antidiabetic medicinal plant that acts by inhibiting the α-amylase enzyme. Andrographolide, the active compound of sambiloto leaf, is insoluble in water but dissolves in ethanol. Aim: This study compared the in vitro activity of aqueous extract and ethanolic extract of sambiloto leaf with the α-amylase enzyme. Methods: The inhibitory activity test of the α-amylase enzyme was carried out using the ultraviolet-visible spectrophotometric method by measuring the absorbance of the remaining starch, which forms a blue complex with iodine-iodide. Results: The inhibitory activity of the α-amylase enzyme of the aqueous extract of sambiloto leaf (with the IC50 value of 14.203 ± 0.112 mg/mL) was lower than that of the ethanol extract (with the IC50 value of 9.253 ± 0.116 mg/mL). The results of the statistical tests showed significant differences (p

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.