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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.

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.

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).

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.

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.

Objective Huidouba (HDB) is a Chinese folk medicine used to treat diabetes in Sichuan Province, China. Therefore, we investigated the anti-diabetic effects of HDB and its underlying mechanisms. We hypothesized that HDB treatment could enhance glucose tolerance and insulin sensitivity, and thus prevent a hyperglycemia state. Methods To test the hypothesis, streptozotocin (STZ)-induced diabetic mice and db/db mice, widely used models of hyperglycemia and insulin-resistant diabetes, were either treated with HDB, metformin, or acarbose. Blood glucose, oral glucose tolerance test, insulin tolerance test, pancreatic histopathology and serum biochemistry were detected to assess the hypoglycemic effect of HDB. Results HDB treatments were found to show the effect in reducing glucose levels. HDB also resulted in a significant reduction in body weight and food intake in the STZ-induced diabetic mouse model. Furthermore, it significantly improved glucose and insulin tolerance in the two diabetic mouse models. Importantly, insulin, glucagon, pancreatic polypeptide, and somatostatin immunohistochemistry revealed that HDB treatment improved the function and the location of the cells in the islets compared with the other two treatments. HDB treatment resulted in significant restoration of islet function. Our results illustrated the underlying mechanism of HDB in the progression of diabetes, and HDB can be an effective agent for the treatment of diabetes. Conclusion The results of this study suggested that HDB can reduce blood glucose levels in STZ-induced hyperglycemic mice and db/db mice.

Mushrooms have been used as a primary source of medicines since ancient times due to the presence of bioactive compounds. Enzyme inhibition is an important field of pharmaceutical research that provides insight into the discovery of a large variety of drugs that are useful in treating many diseases. The inhibitory activities of the hexane and methanol extracts of twenty-four medicinal mushrooms on α-amylase and α-glucosidase enzymes related to type 2 diabetes were evaluated in this study. Among all studied mushroom extracts, C. rutilus hexane extract (IC50: 0.05±0.01 mg/mL) demonstrated the highest inhibitory activity on α-amylase while P. ostreatus hexane (IC50: 0.10±0.01 mg/mL) showed the highest inhibitory activity on α-glucosidase. The hexane extracts of C. rutilus (98.81±0.01 %), G. adspersum (96.96±0.47 %), G. sepiarium (96.89±1.01 %), and S. granulatus (97.74±0.27 %) displayed higher inhibitory activity on α-amylase enzyme than acarbose at 1.00 mg/mL concentration. Also, the hexane extracts of P. ostreatus (IC50: 0.10±0.01 mg/mL), M. procera (IC50: 0.11±0.01 mg/mL), P. schweinitzii (IC50: 0.14±0.01 mg/mL), L. gentianeus (IC50: 0.22±0.02 mg/mL), P. pini (IC50: 0.22±0.03 mg/mL) and the methanol extracts of T. pubescens (IC50: 0.12±0.02 mg/mL) and G. adspersum (IC50: 0.20±0.04 mg/mL) showed higher inhibitory activity on α-glucosidase enzyme than acarbose (IC50: 0.37±0.01 mg/mL). This study with the reported results supported the use of mushrooms in the pharmaceutical industries as natural antidiabetic agents through key enzyme inhibition.

Tsaokols A (1) and B (2), two complicated flavanol-monoterpenoid hybrids, were isolated from the dried fruits of Amomum tsao-ko under the guidance of LCMS and bioassay. Their structures were determined by extensive spectroscopic analyses and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 shared a flavanol backbone fused with 5/7 and 5/6 bicyclic monoterpenoid scaffolds, which were biogenetically condensed by Michael addition and acetalization. Compounds 1 and 2 exhibited significant α-glucosidase inhibitory activity with IC50 values of 18.8 and 38.6 μmol/L (acarbose, IC50 = 213 μmol/L). Docking study supported the strong interactions of 1 and 2 bonding with enzyme by mainly hydrophobic and hydrogen-bond effects. Compounds 1 and 2 could be fast distinguished by the diagnostic ions at m/z 289 and 313 in negative MS2 experiments.

The inhibitory effects of chitooligosaccharide-epigallocatechin gallate (COS-EGCG) conjugate in comparison with COS, EGCG, and acarbose on α-amylase were studied. The half-maximum inhibitory concentration (IC

In this study, we have investigated a series of hydroxylated 2-phenylbenzofurans compounds for their inhibitory activity against α-amylase and α-glucosidase activity. Inhibitors of carbohydrate degrading enzymes seem to have an important role as antidiabetic drugs. Diabetes mellitus is a wide-spread metabolic disease characterized by elevated levels of blood glucose. The most common is type 2 diabetes, which can lead to severe complications. Since the aggregates of islet amyloid polypeptide (IAPP) are common in diabetic patients, the effect of compounds to inhibit amyloid fibril formation was also determined. All the compounds assayed showed to be more active against α-glucosidase. Compound 16 showed the lowest IC50 value of the series, and it is found to be 167 times more active than acarbose, the reference compound. The enzymatic activity assays showed that compound 16 acts as a mixed-type inhibitor of α-glucosidase. Furthermore, compound 16 displayed effective inhibition of IAPP aggregation and it manifested no significant cytotoxicity. To predict the binding of compound 16 to IAPP and α-glucosidase protein complexes, molecular docking studies were performed. Altogether, our results support that the 2-phenylbenzofuran derivatives could represent a promising candidate for developing molecules able to modulate multiple targets involved in diabetes mellitus disorder.

Searching for bioactive agents from Vietnamese plants, nine compounds, including five nor-lignan-type benzofurans 1–5, two lignans 6 and 7, one sterol 8 and one triterpenoid 9 were separated from Styrax argentifolius for the first time. 5-((E)-2-Carboxyvinyl)-7-methoxy-2-(3′,4′-methylenedioxyphenyl)benzofuran (1) and 5-carboxy-7-methoxy-2-(3′,4′-methylenedioxyphenyl)benzofuran (2) were new benzofurans in nature. Sterol (20R)-24-ethylcholest-5,22-dien-7-one (8) and triterpenoid 2α,3α,24-trihydroxy-urs-12-en-28-oic acid (9) were isolated from the genus Styrax for the first time. Egonol (3) showed potential IC50 values of 18.15–22.11 μg/mL against three cancer cell lines KB, HepG2 and Lu, while the IC50 values of new compound 1, (–)-machicendiol (4), and triterpenoid 9 were comparable with that of the positive control acarbose (IC50 118.43 ± 2.44 μg/mL) in α-glucosidase inhibitory assays. Styrax benzofurans and triterpenoids show cytotoxic and α-glucosidase inhibitory activities. The activities of benzofurans 1 and 3–5 were due to the effect of propyl side chains at carbon C-5.

Two new cadinane sesquiterpenes, cadinoschanes A and B (1 and 2), one new norlignan, lignanoschane A (6) along with seven known compounds, hibiscone B (3), 7β-O-β-glucopyranosyl bombaxone (4), 2,7β,8β-trihydroxy trans-calamenene 7-O-β-D-glucopyranoside (5), clemastanin A (7), (−)-3,4,3′,4′-tetrahydroxy-9,7′β-epoxylignano-7β,9′-lactone (8), N-trans-feruloyl tyramine (9), and methyl (3R)-3-[(3R)-3-{(3R)-3-hydroxybutanoyloxy} butanoyloxy} butanoate (10) were isolated from Abelmoschus moschatus subsp. tuberosus (Span.) Borss. Waalk. Their structures were determined on the basis of extensive spectroscopic methods, including 1D, 2D NMR and MS data and comparing experimental CD with theoretical CD calculations. Compounds 3 and 9 showed significant α-glucosidase inhibitory activity with IC50 values of 121.7 ± 3.9 and 4.3 ± 0.5 μg/mL, respectively, compared to those of a positive control, acarbose with IC50 value of 183.5 ± 12.2 μg/mL.

Acarbose and voglibose are α -glucosidase inhibitors that have been used for controlling of diabetes mellitus. Unfortunately, these drugs have many side effects. Consequently, the discovery of new agents with high α -glucosidase inhibitory activity and weak side effects becomes of great importance. To that end, a set of 23 benzothiazole compounds have been studied using 3D-QSAR modeling and molecular docking simulation in order to predict new molecules with important α -glucosidase inhibitory activity. CoMFA and CoMSIA models using eighteen compounds in the training set give significant Q2 values of 0.553 and 0.75, and important R2 values of 0.93 and 0.942, respectively. The five remaining molecules wereemployed in order to test the proficiency of 3D-QSAR models and the predicted determination coefficients R2test values are 0.74 and 0.87 for CoMFA and CoMSIA models, respectively. CoMFA and CoMSIA contour maps were afforded much helpful information to determine the preferred and unpreferred regions impacting the activity; as a result, we propose new benzothiazole compounds with important predicted activities. Meanwhile, to guess the interaction between a newly designed compounds and the most active molecule (compound 8) with α-glucosidase receptor (PDB ID: 3L4T), a molecular docking was conducted. The docking outcomes elucidated that the predicted compound X1 was stable in the active pocket of α-glucosidase receptor. Finally, the newly benzothiazole compounds have been assessed for their oral bioavailability and toxicity using ADMET properties and drug likeness. These findings would be of great aid in leading optimization for new drug discovery that can resolve the biggest challenge related of diabetes mellitus.

Background: Postbariatric hypoglycemia (PBH) is a potentially serious complication after Roux-en-Y gastric bypass (RYGB), and impaired counterregulatory hormone responses have been suggested to contribute to the condition. Objectives: We evaluated counterregulatory responses during postprandial hypoglycemia in individuals with PBH who underwent RYGB. Setting: University hospital. Methods: Eleven women with documented PBH who had RYGB underwent a baseline liquid mixed meal test (MMT) followed by 5 MMTs preceded by treatment with (1) acarbose 50 mg, (2) sitagliptin 100 mg, (3) verapamil 120 mg, (4) liraglutide 1.2 mg, and (5) pasireotide 300 μg. Blood was collected at fixed time intervals. Plasma and serum were analyzed for glucose, insulin, glucagon, epinephrine, norepinephrine, pancreatic polypeptide (PP), and cortisol. Results: During the baseline MMT, participants had nadir blood glucose concentrations of 3.3 ±.2 mmol/L. At the time of nadir glucose, there was a small but significant increase in plasma glucagon. Plasma epinephrine concentrations were not increased at nadir glucose but were significantly elevated by the end of the MMT. There were no changes in norepinephrine, PP, and cortisol concentrations in response to hypoglycemia. After treatment with sitagliptin, 8 individuals had glucose nadirs

Hermannia geniculata roots are commonly used in the treatment of several diseases in Sotho traditional medicine. A new xanthene derivative, Hermannol (9-(7-methyloctyl)-9H- xanthene-2,3-diol) was isolated from the roots of Hermannia geniculata. The structure was elucidated by analyses of their 1Dimensional and 2Dimensional Nuclear Magnetic Resonance, Mass Spectrometry and Infrared Spectroscopic data. In-vitro antioxidant, antidiabetic and antinflammatory evaluation of the compound using standard procedure showed that the compound has good radical scavenging capabilities against DPPH radicals with an IC50 value of 0.29 ± 0.011 mg/mL which is similar to the IC50 value 0.24 ± 0.020 mg/mL of the standard. Also, the metal-chelating properties of the compound is similar to the reference compound with their respective IC50 values (0.28 ± 0.074 and 0.029 ± 0.091) mg/mL. Inhibitory properties of hermannol against carbohydrate catabolizing enzymes, showed a lower inhibition of α-amylase with an IC50 value of 0.59 ± 0.086 mg/mL which is higher than standard drug (acarbose) with IC50 value of 0.43 ± 0.069 mg/mL. Also, it demonstrated higher inhibition of α-glucosidase enzyme with an IC50 value of 0.04 ± 0.002 mg/mL, this is lower than acarbose with an IC50 value of 0.16 ± 0.001 mg/mL. In addition, hermannol showed higher inhibition of 5-lipoxygenase enzyme than indomethacin (standard) with their respective IC50 values of (0.67 ± 0.042 and 1.07 ± 0.064) mg/mL. These results showed that hermannol, a new compound isolated from the root of H. geniculata may be used in the management of inflammation, oxidative stress-induced diseases and type 2 diabetes mellitus.

Inhibition of α-glucosidase activity is an effective way for treatment of type 2 diabetes mellitus. Epimedii Folium is an important source of α-glucosidase inhibitors (AGIs), however bioactive compounds and pharmacological mechanisms remained unclear. In this study, a novel strategy was established, which harnessed α-glucosidase functionalized magnetic beads to fish out potential AGIs, followed by UPLC-MS/MS analysis for their identification. Furthermore, molecular docking was employed to predict binding patterns between the AGIs and the enzyme, and IC50 values was estimated as well. After response surface methodology optimization, the highest activity of Fe3O4@α-glucosidase has been achieved when 1.17 mg/mL of α-glucosidase was immobilized in phosphate buffer (pH 6.81) for 4.22 h. Moreover, eight flavonoids were fished out from the extract of Epimedii Folium, and then identified to be epimedin A, epimedin B, epimedin C, icariin, sagittatoside A, sagittatoside B, 2"-O-rhamnosyl icariside II and baohuoside I. All of them were further confirmed to be AGIs through in vitro inhibitory assay and molecular docking. Among those, baohuoside I and sagittatoside B possessed stronger inhibitory activity than acarbose. The approach has a significant prospect in conveniently screening bioactive compounds that target various receptors, which provided an efficient platform for new drug development from natural products.

The optimum extraction conditions of polysaccharides from roxburgh rose (Rosa roxburghii Tratt.) leaves (RLP) were obtained by response surface methodology (RSM), which were a liquid to solid ratio of 21.16 mL/g, an extraction temperature of 81.32 °C, and an extraction time of 90.49 min. An RLP yield of 11.04% was obtained under these conditions. DEAE-52 cellulose and Sepharose CL-6B columns were used to purify the RLP, and the purified polysaccharide components RLP-1.2 and RLP-2.1 were obtained. Both RLP-1.2 and RLP-2.1 were composed of galacturonic acid (GalA), glucose (Glc), galactose (Gal), and arabinose (Ara). However, the molar ratios of GalA, Glc, Gal, and Ara in RLP-1.2 and RLP-2.1 were different. At a concentration of 10 mg/mL, the α-amylase inhibitory activities of RLP-1.2 and RLP-2.1 reached 80.74% and 89.85% that of acarbose, respectively, and the α-glucosidase inhibitory activity of RLP-1.2 reached 87.91% that of acarbose. In addition, both RLP-1.2 and RLP-2.1 showed good antioxidant activity. These results suggested that RLP-1.2 and RLP-2.1 possess potential as natural hypoglycemic agents or natural antioxidants.

Benzene is a well-known human carcinogen that is one of the major components of air pollution. Sources of benzene in ambient air include cigarette smoke, e-cigarettes vaping and evaporation of benzene containing petrol processes. While carcinogenic effects of benzene exposure have been well studied, less is known about metabolic effects of benzene exposure. We show that chronic exposure to benzene at low levels induces severe metabolic imbalance in a sex-specific manner, which is associated with hypothalamic inflammation and endoplasmic reticulum (ER) stress. Benzene exposure rapidly activates hypothalamic ER stress and neuroinflammatory responses in male mice, while pharmacological inhibition of ER stress response by inhibiting IRE1α-XBP1 pathway significantly alleviates benzene-induced glial inflammatory responses. Additionally, feeding mice with Acarbose, a clinically available anti-diabetes drug, protected against benzene induced central and peripheral metabolic imbalance. Acarbose imitates the slowing of dietary carbohydrate digestion, suggesting that choosing a diet with a low glycemic index might be a potential strategy for reducing the negative metabolic effect of chronic exposure to benzene for smokers or for people living/working in urban environments with high concentrations of exposure to automobile exhausts.

Two new prenylated flavonoids named 4',1”-dihydroxy-3'-methoxy-6,7-furanflavanone (1), 5,3',4'-trihydroxy-1”-methoxy-6,7-furanbavachalcone (2), together with six known compounds (3-8), were isolated from the seeds of Psoralea corylifolia. The chemical structures were elucidated on the basis of spectroscopic analyses including MS and NMR spectrometry. All isolates were evaluated for in vitro inhibitory activity against α-glucosidase. And compound 1 showed moderate inhibitory activity on α-glucosidase with IC50 value of 53.1 μM, compared with the 214.5 μM of positive control acarbose.

Background The inhibition of α-amylase and α-glucosidase activities is one of the major practical strategies for the control of postprandial hyperglycemia. Salvia officinalis L. is known by its various bioactive compounds and its effective therapeutic properties towards illnesses including diabetes. Objective The present study aimed to evaluate the in vitro inhibitory effect of S. officinalis on key digestive enzymes linked to type 2 diabetes and to identify its hemolytic effect. Methods Hydro-methanol decoction extract and fractions of ethyl acetate and n-butanol were investigated for their in vitro α-amylase and α-glucosidase inhibitory activities, compared to acarbose as a standard. Furthermore, they were evaluated for their hemolytic effect. Results Phytochemical composition demonstrated the richness of S. officinalis in secondary metabolites. Extract and fractions inhibited the activity of both enzymes. They showed weak hemolytic activity. Quantitative estimation of total phenolic and flavonoids revealed that ethyl acetate fraction contained the highest amount of these compounds (450.51 ± 0.6 μg GAE/mg DE and 352.01 ± 0.78 μg CE/mg of DE, respectively). It showed the best antidiabetic activity tested both by α-amylase and α-glucosidase assays (IC50 = 46.52 ± 2.68 and 104.58 ± 0.06 μg/mL, respectively). Moreover, this fraction showed the least hemolytic effect (11.58 ± 0.1%). Conclusions S. officinalis extract and fractions are promising sources of α-amylase and α-glucosidase inhibitors.

α-Glucosidase and α-amylase are enzymes which are associated with diabetic II. These enzymes break macromolecules of sugar into monosugar molecules which is soluble in body, hence increase the sugar level in blood. There is need to develop economical and save inhibitors to prevent them from breaking sugar macromolecules to soluble molecules which will control the level of sugar in blood. Therefore, we synthesized indole-based derivatives (1–18) and evaluated as dual inhibitor for α-glucosidase and α-amylase. These chemical scaffolds were built with variation in aryl ring which were found active with good to moderate activity for α-glucosidase having IC50 value ranging from 13.99 ± 0.10 to 59.09 ± 0.30 μM when compared with standard acarbose with IC50 of 11.29 ± 0.10 μM; for α-amylase IC50 value ranging from 13.14 ± 0.10 to 58.99 ± 0.30 μM when compared with the standard acarbose with IC50 of 11.12 ± 0.10 μM. Structure activity relationship (SAR) has been established for all compounds. Enzymatic kinetic study and molecular docking study have been carried out to investigate the binding interactions α-glucosidase and α-amylase enzyme.

Three new pregnane glycosides namely volubilosides D-F (1–3) along with three known, dregeoside Da1 (4), volubiloside A (5), and drevoluoside N (6) were isolated from the methanol extract of the leaves of Dregea volubilis using combined chromatographic methods. Their structures were elucidated by 1D-, 2D-NMR, and HR-ESI-MS spectra and comparing with those reported in the literature. Compounds 5 and 6 showed the most significant α-glucosidase inhibitory activity at the concentration of 40 μM with inhibition of 51.3 ± 3.2% and 50.4 ± 3.1%, respectively, compared to acarbose (59.8 ± 1.6%).

Excessive production of free radicals in the living system leads to oxidative stress which is associated with degenerative disorders including diabetes. Diabetes is increasing at a rapid pace despite the availability of synthetic anti-hyperglycemic drugs in the market. Hence antioxidant and anti-diabetic compounds of natural origin have attracted attention for drug development. The aim of the present study was to investigate the phytochemical composition, antioxidant potential, α-amylase inhibitory and antidiabetic activity of aqueous (AQ) and ethyl acetate (EA) extracts of Terminalia bellirica fruit. Chemical methods were employed for phytochemical analysis. Antioxidant activities of extracts were measured using in vitro assays viz., DPPH free radical scavenging, reducing power, hydroxyl radical scavenging and phosphomolybdate assays. The antidiabetic potential was measured by in vitro α-amylase inhibitory activity and in vivo serum biochemical assays in alloxan-induced diabetic rats. Chemical analysis showed the presence of phenols, flavonoids, alkaloids, terpenoids, saponins and glycosides as a major phytochemical in AQ and EA extracts of T. bellirica fruit. Quantitatively EA extract showed the presence of higher content of phenolics and flavonoids as compared to AQ extract. Further EA extract exhibited considerable free radical scavenging abilities in DPPH and HRSA assays (up to 94%), reducing power assay and appreciable total antioxidant power in phosphomolybdate assay (78 μgPGE/g). The EA extract exhibited comparatively better α-amylase inhibitory activity (IC50 43.5 μg/ml) as compared to AQ extract (IC50 74.8 μg/ml). The activity was comparable to standard drug acarbose. Antidiabetic activity of extracts was studied in alloxan-induced diabetic rats by monitoring the body weight, blood glucose, lipid profile and other biochemical parameters for 28 days. In diabetic rats both the extracts showed a restorative effect on body weight and blood biomarkers such as glucose, creatinine, total protein, total cholesterol, LDL, HDL, triglyceride, urea and uric acid. The ethyl acetate extract also exhibited superiority over the aqueous extracts during in vivo antidiabetic assays. The results revealed that T. bellirica fruit extracts possess antioxidant, α-amylase inhibitory and antidiabetic activities and hence it could be useful for the management of hyperglycemia and oxidative stress.

Three new pregnane glycosides in addition to four known compounds were isolated from the methylene chloride fraction of Caralluma hexagona Lavranos using bioassay-guided fractionation. The new compounds were identified as 12,20-di-O-benzoyl-3β,8β,12β,14β,20-pentahydroxy-(20R)-pregn-5-ene-3-O-β- d -glucopyranosyl-(1→4)-β- d -digitaloside (1), 3β,8β,14β,20-tetrahydroxy (20R)-pregn-5-ene-3-O-β- d -glucopyranosyl-(1→4)-O-β- d -digitaloside-20-O-β– d -glucopyranoside (2), 3β,8β,14β,20-tetrahydroxy-(20R)-pregn-5-ene-3-O-β- d -glucopyranosyl-(1→6)-O-β- d -glucopyranosyl-(1→4)-O-β- d -digitaloside-20-O-β– d -glucopyranoside (3), along with the known compounds luteolin 4`-O-neohesperidoside (4), apigenin-8-C-neohesperoside (5), β-sitosterol (6) and β-sitosterol glucoside (7). Preliminary studies of the crude methanolic extract and methylene chloride fraction showed inhibitory effects against α-glucosidase and pancreatic lipase. Among the isolated compounds, compound 5 showed the most potent α-glucosidase inhibition with IC50 value of 0.82 ± 2.50 μM compared to acarbose (0.81 ± 0.86 μM). Whereas compound 1 showed the highest inhibitory activity on pancreatic lipase with an IC50 value of 23.59 ± 2.49 μM compared to orlistat (7.41 ± 2.26 μM).

α-Glucosidase enzyme is a therapeutic target for diabetes mellitus and its inhibitors play a vital role in the treatment of this disease. A new series of aryl-oxadiazole Schiff bases (1–18) were synthesized and evaluated for α-glucosidase inhibitory potential. Fifteen compounds 1–8, 11–13, and 15–18 showed excellent inhibition with IC50 values ranging from 0.30 ± 0.2 to 35.1 ± 0.80 µM as compared to the standard inhibitor acarbose (IC50 = 38.45 ± 0.80 µM), nonetheless, the remaining compounds were found to have moderate activity. Among the series, compounds 7 (IC50 = 0.30 ± 0.2 μM) with hydroxy groups at phenyl rings on either side of the oxadiazole ring was identified as the most potent inhibitor of α-glucosidase. The molecular docking studies were conducted to understand the binding mode of active inhibitors with the active site of enzyme and results supported the experimental data. Keywords: Synthesis, Aryl-oxadiazole Schiff bases, α-glucosidase, Molecular docking, Structure-activity relationship (SAR)

Three new compounds comprising two coumarins, paramicoumarins A (1) and B (2), and an acridone alkaloid, paramiacridone (3), together with seven known compounds, were isolated from the n-hexane extract of the roots of Paramignya trimera (Rutaceae). Their structures were elucidated using spectroscopic methods, mainly 1D and 2D NMR. α-Glucosidase inhibition and DPPH radical scavenging activity of the compounds and fifteen other compounds previously isolated from the roots of this plant were evaluated. Most of the compounds exhibited stronger α-glucosidase inhibitory activity than acarbose, the positive control (IC50 = 223.0 μM), and the new compounds paramiacridone (3) and paramicoumarin B (2) showed good inhibitory effect (IC50 = 62.5 and 65.5 μM, respectively). In the DPPH test for radical scavenging activity, the acridone alkaloid glycocitrin III (17) exhibited the highest antioxidant activity (IC50 = 84.2 μM) (compared with the positive control, ascorbic acid, IC50 = 152.7 μM).

α-Glucosidase is an important enzyme in human intestine, and inhibition of its activity can lower blood sugar levels to effectively prevent hyperglycaemia induced tissue damage. Here, we investigated the inhibitory activities of procyanidins with different structures on α-glucosidase and the underlying mechanism. The results showed that the IC50 of catechin and compounds 2-7 on α-glucosidase was lower than that of acarbose. A-type procyanidins might have better inhibitory activity than B-type procyanidins. In addition, there was no positive correlation between the polymerization degree of A-type procyanidin oligomer and its inhibitory effect on α-glucosidase. Compound 7 (A-type trimer) with the best inhibitory effect reversibly inhibited the activity of α-glucosidase in a mixed-type manner. Fluorescence data confirmed that the intrinsic fluorescence of α-glucosidase was quenched by compound 7 through static-dynamic quenching. The calculated thermodynamic parameters indicated that their binding was spontaneous and driven by hydrophobic interaction, which was also confirmed by the UV spectrum experiment. Besides, circular dichroism analysis displayed that their binding resulted in conformational changes of α-glucosidase characterized by a decrease in α-helix and an increase in β-sheet. The results demonstrate the ability of procyanidins to intervene in the progression of type 2 diabetes by inhibiting α-glucosidase.

Moringa oleifera is a source of food, shelter and traditional medicine for many people in developing countries. It is an exceptional source of vitamins, minerals, amino acids, lipids, carotenoids, flavonoids, sterols and phenolics. Owing to its diverse nutritional and phytochemical composition, it is widely consumed and used in therapeutics. In this study, the aqueous, methanol, hexane and ethyl acetate extracts of M. oleifera seeds, leaves and roots were assessed for in vitro α-amylase, α-glucosidase and glucose-induced bovine serum albumin glycation inhibition. Findings indicate that methanol and hexane leaves extracts demonstrated highest α-amylase inhibitory activity (IC50 = 8.217 and 9.397 mg/ml respectively), though the activities were lower than that of acarbose (IC50 = 0.036 mg/ml). In contrast, hexane root extract exhibited optimal α-glucosidase inhibition and antiglycation effect (IC50 = 0.382 and 0.772 mg/ml, respectively). The extract activity was higher than that of acarbose (IC50 = 0.884 mg/ml), but lesser than rutin (IC50 = 0.199 mg/ml); which were the control for α-glucosidase inhibition and antiglycation studies respectively. In conclusion, suggesting its potentials in regulating postprandial blood glucose, and attenuating the production/accumulation of advanced glycation end product. Thus, M. oleifera extracts exhibited promising antidiabetic activity.

α-Glucosidase inhibitors are widely used to suppress postprandial glycemia in the treatment of type 2 diabetes mellitus. The present study evaluated the in vitro α-glucosidase inhibitory activity of three major pigment constituents of Cinnamomum camphora fruit, namely cyanidin, cyanidin 3-rutinoside, and cyanidin-3-O-glucoside. We found that cyanidin exerted strong inhibitory activity on α-glucosidase, with IC50 of 5.293 × 10−3 mM, whereas cyanidin 3-rutinoside and cyanidin-3-O-glucoside did not show inhibitory activity on α-glucosidase. The inhibitory activity of cyanidin was stronger than that of acarbose (IC50 1.644 mM), the current most commonly used drug for postprandial glycemia. Kinetic analysis indicated that cyanidin inhibited α-glucosidase through competition, with a Ki value of 0.0183 mM. Fluorescence spectrum titration showed only one binding site between cyanidin and α-glucosidase, and the binding constant was calculated. Further, molecular docking was conducted to simulate the binding interactions between cyanidin and α-glucosidase. Cyanidin was found to interact with several residues close to the catalytic site of α-glucosidase through π-π stack interaction and hydrogen bonds. The calculated binding energy of the cyanidin and enzyme complex was −105.031 kJ/mol. Molecular simulation and calculation showed that the van der Waals force played an essential role in the binding of α-glucosidase and cyanidin.

In the present study, a series of cycloalkyl[b]thiophenylnicotinamide derivatives against α-glucosidase were synthesized, and evaluated for their in vitro and in vivo anti-diabetic potential. Most of the synthetic analogues exhibited superior α-glucosidase inhibitory effects than the standard drug acarbose (IC

A new series of syn-functionalised chiral hydroxy pyrrolidines and pyrrolidones containing α,β-contiguous stereocenters were synthesized via a diphenylprolinol-catalysed asymmetric cross aldol reaction. The synthesized compounds were characterised and evaluated for their α-glucosidase inhibitory potential. The hydroxy pyrrolidine series (9a-9i) was found to be selectively more potent against the α-glucosidase enzyme as compared to the pyrrolidone series (10a-10i). Pyrrolidine 9b was the most efficacious analogue with an ICsub50/subof 48.31 µM. Compounds 9c, 9d,amp; 9f were also found to be more potent than the standard drugs acarbose, miglitol and deoxynojirimycin. Furthermore, these compounds were investigated by computational studies using the GLIDE docking module of the Schrödinger suite 2021-4 in which 9b and 9c showed more promising results than the standard drugs acarbose, miglitol, and deoxynojirimycin.

Combination of dietary flavonoid-baicalein and acarbose reduces the risk that prediabetes will develop into type 2 diabetes mellitus; however, the mechanism underlying this effect has not been clarified. In this study, the in vitro culture conditions of intestinal microorganisms from prediabetic mice were optimized to increase over 30% similarity between in vitro cultured and fecal samples. Baicalein and acarbose alone and in combination, and their corresponding starch hydrolysate were assayed by the in vitro model. The results indicated that the combination of baicalein with acarbose decreased gas production by reducing the residual starch ratio in starch hydrolysate and decreasing the dosage of acarbose, and that reducing the relative abundance of gut bacteria correlated with gas production is the main mechanism. This study provided a theoretical foundation for the development of flavonoid dietary supplements to enhance the efficacy of oral hypoglycemic agents with fewer side effects and higher efficacy.

In the development of novel anti-α-glucosidase agents, we synthesized novel thieno[2,3-b]quinoline-hydrazones 9a-n by facile and efficient conventional chemical reactions. These compounds were characterized by IR

The prevalence of diabetes mellitus has been incremented in the current century and the need for novel therapeutic compounds to treat this disease has been significantly increased. One of the most promising approaches is to inhibit intestinal alpha glucosidases. Based on our previous studies, four pyrimidine-fused heterocycles (PFH) were selected as they revealed satisfactory inhibitory action against mammalian α-glucosidase. The interaction of these compounds with both active domains of human maltase-glucoamylase (MGAM) and their effect on human Caco-2 cell line were investigated. The docking assessments suggested that binding properties of these ligands were almost similar to that of acarbose by establishing hydrogen bonds especially with Tyr1251 and Arg526 in both C-terminal and N-terminal MGAM, respectively. Also, these compounds indicated a stronger affinity for C-terminal of MGAM. L2 and L4 made tightly complexes with both terminals of MGAM which in turn revealed the importance of introducing pyrimidine scaffold and its hinge compartment. The results of molecular dynamics simulation analyses confirmed the docking data and showed deep penetration of L2 and L4 into the active site of MGAM. Based on cell cytotoxicity assessments, no significant cell death induction was observed. Hence, these functional MGAM inhibitors might be considered as new potential therapeutic compounds in treatment of diabetes and its complications.

Coreopsis tinctoria is being widely cultivated in Xinjiang of China, whose consumption is known to prevent diabetes and neurodegenerative diseases. To elucidate the bioactive ingredients responsible for these benefits, the alkaline soluble crude polysaccharide (CTB) was isolated from C. tinctoria. In vitro experiments showed that the inhibition of α-amylase and α-glucosidase by CTB was 13407-fold and 906-fold higher than that by positive control, respectively. Then, a novel arabinogalactan, CTBP-1, was isolated and purified from CTB. Structural analysis showed that CTBP-1 possessed a 1,6-linked β-d-Galp and 1,5-linked α-l-Araf backbone with branches substituted at the C-3 position of the 1,6-linked β-d-Galp, and the side chains included 1,5-linked α-l-Araf, T-linked β-d-Galp and T-linked α-l-Araf. The inhibitory effects of CTBP-1 on α-amylase and α-glucosidase were 2.7 and 17.9 times that of acarbose, respectively. CTBP-1 could avoid indigestion and similar side effects. In addition, CTBP-1 remarkably inhibited the release of nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. In summary, CTBP-1 is a novel arabinogalactan with great potential as a treatment for type 2 diabetes and Alzheimer's disease.

In searchof the potenttherapeutic agent as an α-glucosidase inhibitor, we have synthesized twenty-five analogs (1–25) of quinoline-based Schiff bases as an inhibitoragainst α-glucosidase enzyme under positive control acarbose (IC50 = 38.45 ± 0.80 µM). From the activity profile it was foundthat analogs 1, 2, 3, 4, 11, 12 and 20with IC50values 12.40 ± 0.40, 9.40 ± 0.30, 14.10 ± 0.40, 6.20 ± 0.30, 14.40 ± 0.40, 7.40 ± 0.20 and 13.20 ± 0.40 µMrespectively showed most potent inhibition among the series even than standard drug acarbose (IC50 = 38.45 ± 0.80 µM). Here in the present study analog 4 (IC50 = 6.20 ± 0.30 µM) was found with many folds better α-glucosidase inhibitory activity than the reference drug. Eight analogs like 5, 7, 8, 16, 17, 22, 24 and 25 among the whole series displayed less than 50% inhibition. The substituents effects on phenyl ring thereby superficially established through SAR study. Binding interactions of analogs and the active site of ligands proteins were confirmed through molecular docking study. Spectroscopic techniques like 1H NMR, 13C NMR and ESIMS were used for characterization.

A new series of thiosemicarbazide-1,2,3-triazole hybrids 10a-o has been synthesized, characterized by 1H NMR, 13C NMR, and screened for their in vitro α-glucosidase inhibitory activity. All of the synthesized compounds displayed excellent α-glucosidase inhibitory activity with IC50 values in the range of 75.0 ± 0.5 to 253.0 ± 0.5 μM, as compared to the standard drug acarbose (IC50 = 750.0 ± 1.5 μM). Among the synthesized compounds, compound 10h (IC50 = 75.0 ± 0.5) with 4-methoxy group at phenyl part of thiosemicarbazide moiety and 2,6-dichloro substituents at benzyl moiety was found to be the most potent compound. Kinetic analysis revealed that compound 10h is a competitive inhibitor for α-glucosidase. Docking study of compound 10h in the active site of α-glucosidase showed that this compound interacted with residues His239, His279, Glu304, Gly306, and Arg312.

A mixture of gymnemic acids was precipitated from the water extract of leaves of Gymnema sylvestre (Retz.) R.Br. ex Sm. (Asclepiadaceae) by acidification with 2 N H2SO4. The chromatographic separation of the mixture afforded five new gymnemic acids (1-5). The compounds were characterized as Δ15 oleanane glycosides on the basis of extensive spectral data analysis. The compounds (1-5) showed dose dependent inhibition of α-glucosidase, which was found to be comparable to acarbose (IC50 95 μg/ml). Maximum inhibition was achieved with compound 4 (IC50 57 μg/ml) followed by 3 (IC50 62 μg/ml), 1 (IC50 80 μg/ml), 2 (IC50 120 μg/ml) and 5 (IC50 128 μg/ml). The results revealed that the overall pattern of hydroxyl and acyl substitutions of compounds affected their inhibitory activity. In oral sucrose tolerance test, pre-treatment with crude gymnemic acid mixture and isolated compounds 1 and 4 at a dose of 10 mg/Kg b.w. significantly blunted the effect of sucrose challenge in mice. Based on these results, the antihyperglycemic effect of G. sylvestre can be, at least partly, attributed to the inhibition of α-glucosidase by its gymnemic acids. The current study provides relatively more direct evidence explaining the effectiveness of G. sylvestre against hyperglycemia.

α-Glucosidase enzyme inhibition is an effective therapeutic decorum in the treatment of type 2 diabetes mellitus. Since 1990, three α-glucosidase inhibitors are known to exist clinically, Acarbose, Voglibose and Miglitol. Side effects and long synthetic routes to access them forced the researchers to move their focus to discover simple and small heterocyclic motifs that work as promising α-glucosidase inhibitors and may eventually lead to the management of postprandial hyperglycemic condition in T2DM. In this regards, this review deals with recently discovered heterocyclic molecules that have been evaluated to exhibit inhibition of α-glucosidase enzyme.

Three new complexes formulated as [Cu(mbmb)2Cl2] (1), [Cu(mbmb)2(NO3)2] (2), and [Zn(mbmb)2Cl2] (3) (mbmb = 1-[(2-methyl-1H-benzoimidazol-1-yl)methyl]-1H-benzotriazole) have been synthesized and characterized. Complexes 1–3 showed mononuclear structures and the central metal ions of complexes 1–3 exhibited a four-coordinated environment. We evaluated the antioxidant activity against DPPH and antidiabetic activity against α-amylase of complexes 1–3 and ligand (mbmb) in vitro. The results of DPPH free radical scavenging assay showed that complexes 1 and 2 exhibited higher antioxidant activity among the synthesized compounds and their IC50 values were 43.72 μg/mL and 43.76 μg/mL, respectively. The IC50 values in vitro antidiabetic studies of complex 1 (0.74 mg/mL) and complex 2 (1.00 mg/mL) were much smaller than those of standard acarbose (2.34 mg/mL) and the ligand mbmb (39.87 mg/mL), which showed effective inhibition on α-amylase. Additionally, the solid-state fluorescent properties of these three complexes and ligand mbmb were investigated at room temperature.

This study was carried out to study the effects of selenylation on physicochemical and biological properties of polysaccharide (SPP) extracted from Sargassum pallidum. The selenized derivative of SPP (Se-SPP) with the selenium content of 2419 μg/g was synthesized by sodium selenite/dilute nitric acid method. Physicochemical characterization indicated that selenylation modification resulted in some changes in chemical composition, monosaccharide composition, molecular weight and surface morphology of polysaccharides. FT-IR spectroscopy showed that a new absorption peak appeared at 675 cm−1 in Se-SPP probably due to the substitution of selenyl groups. Bioactivity assay showed that Se-SPP exhibited higher scavenging radical activities and ferrous ion chelating activities than native SPP. Compared with SPP and acarbose, Se-SPP showed more significantly inhibitory effect on α-glucosidase activity in a noncompetitive inhibition type. The IC50 values of SPP, Se-SPP and acarbose were determined as 1.579, 0.896 and 2.742 mg/mL, respectively. These results suggest that Se-SPP can be used to develop a new selenium-complementary ingredient in functional foods.

Red rice (Oryza punctata) is a type of unpolished rice which has higher nutritional value compared to white rice or even polished rice. Owing to higher nutritive content and metabolites, dieticians strongly advise red rice for peoples with metabolic disorders including diabetics. However, the mechanism of action and contents of secondary metabolites in Indian red rice variety not reported scientifically. Therefore, the present study aimed to evaluate its mechanism of action through inhibitory effect of α-amylase and α-glucosidase. Initially, the whole grain of red rice was macerated with methanol at room temperature for 2 weeks. Then, the dried and powdered, samples at different concentration (2.5, 10, 40, and 80 μg/mL) were employed to find out in vitro inhibitory effects on α-amylase and α-glucosidase. In addition, an enzyme kinetics of effective extract was calculated by Line-weaver Burk (LWB) plot analysis. Moreover, the valuable metabolites in the efficient methanolic extract were quantified using high performance liquid chromatography (HPLC). The results demonstrated that red rice methanolic extract (RRMEt) possess strong inhibitory activity on α-amylase and α-glucosidase compared with acarbose (P

Insulin autoimmune syndrome (IAS) is a relatively rare cause of hypoglycemia characterized by endogenous hyperinsulinism and autoantibodies against endogenous insulin despite no prior exposure to exogenous insulin. We present a series of IAS cases and describe the clinical characteristics of these cases.The medical records of inpatients with the final diagnosis of IAS were collected from August 2007 to August 2017 in Peking Union Medical College Hospital. Clinical characteristics and laboratory test results were summarized. The results of serum glucose, insulin, true insulin, and C-peptide testing during 5-h oral glucose tolerance tests were also summarized. Circulating immune complexes were assessed qualitatively by precipitation with polyethylene glycol (PEG) in some patients.Sixteen patients were included in this study. Insulin autoimmune antibody test results were found positive in 12 patients and weakly positive in 1 patient. Nine patients had an insulin to C-peptide molar ratio1, whereas 6 patients had an insulin to C-peptide molar ratio1. Circulating immune complexes were verified in all 4 patients who had been assessed with PEG. During 5-h oral glucose tolerance tests, the C-peptide level responded earlier to the glucose tolerance and had a shorter peak value period compared with insulin, although C-peptide's fluctuation still lagged behind the glucose fluctuation. Three patients presented with self-limited disease courses or limited disease course after discontinuing use of the sulfhydryl group drugs. Some patients' symptoms were relieved after small frequent meals, and some were relieved after taking acarbose. Only 3 patients took glucocorticoids as the anti-immune therapy.The insulin to C-peptide molar ratios were not consistently1 in patients with confirmed diagnoses of IAS in our study, which suggested the low sensitivity of insulin to C-peptide molar ratio to detect IAS. The therapy in our study also revealed the self-limited disease course of IAS, and despite the effectiveness of anti-immunity therapy, convenient therapy, such as frequent small meals and adding acarbose, performed well in many patients.