Inhibitory activity of α-amylase and α-glucosidase by plant extracts from the Brazilian cerrado

Diabetes mellitus is the most common disease in the world. One therapeutic approach for treating diabetes is inhibition of α-amylase and α-glucosidase activities to reduce postprandial blood glucose levels. In vitro tests showed that several plant extracts from Brazilian cerrado species can inhibit the activity of α-amylase and α-glucosidase. The extracts of Eugenia dysenterica, Stryphnodendron adstringens, Pouteria caimito, Pouteria ramiflora, and Pouteria torta showed strong α-amylase and α-glucosidase inhibitory activity. Eugenia dysenterica, P. caimito, P. ramiflora, and P. torta aqueous extracts exerted the highest activity against α-amylase (IC??) values of 14.93, 13.6, 7.08, and 5.67 μg/mL, respectively) and α-glucosidase (IC?? values of 0.46, 2.58, 0.35, and 0.22 μg/mL, respectively). Stryphnodendron adstringens ethanol extract also exhibited inhibitory activity against both enzymes (IC??) 1.86 μg/mL against α-amylase and 0.61 μg/mL against α-glucosidase). The results suggest that the activity of these cerrado plants on α-amylase and α-glucosidase represents a potential tool for development of new strategies for treatment of diabetes.     

Inhibitors of α-glucosidase and α-amylase from Cyperus rotundus

Context: A methanol extract of Cyperus rotundus L. (Cyperaceae) rhizomes showed inhibitory activity against α-glucosidase and α-amylase, two enzymes involve in carbohydrate digestion.

Objective: Identification of compounds from C. rotundus rhizomes responsible for the inhibition of α-glucosidase and α-amylase.

Materials and methods: Compounds were identified by a phytochemical investigation using combined chromatographic and spectroscopic methods. α-glucosidase and α-amylase inhibitory activities were evaluated by in vitro enzyme inhibition assays.

Results: A new (2RS,3SR)-3,4′,5,6,7,8-hexahydroxyflavane (1), together with three known stilbene dimers cassigarol E (2), scirpusin A (3) and B (4) were isolated. Compound 2 inhibited both α-glucosidase and α-amylase activities while the flavane 1 only showed effect on α-amylase, and compounds 3 and 4 were active on α-glucosidase. All four compounds showed significant 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity.

Discussion: The inhibitory activities against α-amylase and α-glucosidase of the C. rotundus rhizomes were reported for the first time. Stilbene dimers are considered as potent inhibitors of α-glucosidase and promising antihyperglycemic agents.

Conclusion: The isolated compounds may contribute to the antidiabetic property of C. rotundus.     

Evaluation of silver-doped indium oxide nanoparticles as in vitro α-amylase and α-glucosidase inhibitors

Pristine and 2 % silver-doped indium oxide (In₂O₃) nanoparticles, synthesized by solution combustion method, yielded spherical nanoparticles in the range of 20–30 nm. The nanoparticles were stabilized in cubic bixbyite structure as revealed from X-ray diffraction study. In order to evaluate the potential of these nanoparticles to modulate enzyme activity, α-amylase and α-glucosidase were used as model enzymes. Pristine and 2 % silver-doped In₂O₃ nanoparticles demonstrated dose-dependent inhibition of α-amylase and α-glucosidase activities. Pristine In₂O₃ nanoparticles demonstrated 26.4 % (300 µg/mL) and 65.3 % (300 µg/mL) inhibition against α-amylase and α-glucosidase, respectively. In contrast, silver-doped In₂O₃ nanoparticles depicted 94.1 % (300 µg/mL) and 99.6 % (0.18 µg/mL) inhibition against α-amylase and α-glucosidase, respectively. In comparison with acarbose, a standard anti-diabetic drug that depicted absolute inhibition of α-glucosidase activity at 300 µg/mL, 2 % silver-doped In₂O₃ nanoparticles completely inhibited α-glucosidase at a very low concentration (0.18 µg/mL). In view of our results, the activity of α-amylase and α-glucosidase, which are targets for treatment of type 2 diabetes, can be modulated using silver-doped In₂O₃ nanoparticles in the concentration-dependent manner. Therefore, silver-doped In₂O₃ has a potential to be used as a prospective starch blocker.     

New phenylpropanoids and in vitro α-glucosidase inhibitors from Balanophora japonica

Five new phenylpropanoids, named balajaponins A-E (1-5), were isolated from Balanophora japonica, along with 24 known compounds. Among them, three hydrolysable tannins (6-8) showed specific in vitro α-glucosidase inhibition, with IC?? values in the range of 1-4 μM. Kinetic analysis revealed that they all acted in a noncompetitive mode.     

Dieckol isolated from Ecklonia cava inhibits α-glucosidase and α-amylase in vitro and alleviates postprandial hyperglycemia in streptozotocin-induced diabetic mice

This study was designed to investigate whether dieckol may inhibit α-glucosidase and α-amylase activities, and alleviate postprandial hyperglycemia in streptozotocin-induced diabetic mice. Dieckol isolated from Ecklonia cava, brown algae, evidenced prominent inhibitory effect against α-glucosidase and α-amylase. The IC₅₀ values of dieckol against α-glucosidase and α-amylase were 0.24 and 0.66 mM, respectively, which evidenced the higher activities than that of acarbose. Dieckol did not exert any cytotoxic effect in human umbilical vein endothelial cells (HUVECs) at various concentrations (from 0.33 to 2.69 mM). The increase of postprandial blood glucose levels were significantly suppressed in the dieckol administered group than those in the streptozotocin-induced diabetic or normal mice. Moreover, the area under curve (AUC) was significantly reduced via dieckol administration (259 versus 483 mmol min/l) in the diabetic mice as well as it delays absorption of dietary carbohydrates. Therefore, these result indicated that dieckol might be a potent inhibitor for α-glucosidase and α-amylase.     

The α-amylase and α-glucosidase inhibitory activities of the dichloromethane extracts and constituents of Ferulago bracteata roots

Context: Ferulago (Apiaceae) species have been used since ancient times for the treatment of intestinal worms, hemorrhoids, and as a tonic, digestive, aphrodisiac, or sedative, as well as in salads or as a spice due to their special odors.

Objectives: This study reports the α-amylase and α-glucosidase inhibitory activities of dichloromethane extract and bioactive compounds isolated from Ferulago bracteata Boiss. &; Hausskn. roots.

Materials and methods: The isolated compounds obtained from dichloromethane extract of Ferulago bracteata roots through bioassay-guided fractionation and isolation process were evaluated for their in vitro α-amylase and α-glucosidase inhibitory activities at 5000–400?µg/mL concentrations. Compound structures were elucidated by detailed analyses (NMR and MS).

Results: A new coumarin, peucedanol-2′-benzoate (1), along with nine known ones, osthole (2), imperatorin (3), bergapten (4), prantschimgin (5), grandivitinol (6), suberosin (7), xanthotoxin (8), felamidin (9), umbelliferone (10), and a sterol mixture consisted of stigmasterol (11), β-sitosterol (12) was isolated from the roots of F. bracteata. Felamidin and suberosin showed significant α-glucosidase inhibitory activity (IC₅₀ 0.42 and 0.89?mg/mL, respectively) when compared to the reference standard acarbose (IC₅₀ 4.95?mg/mL). However, none of the tested extracts were found to be active on α-amylase inhibition.

Discussion and conclusions: The present study demonstrated that among the compounds isolated from CH₂Cl₂ fraction of F. bracteata roots, coumarins were determined as the main chemical constituents of this fraction. This is the first report on isolation and characterization of the bioactive compounds from root extracts of F. bracteata and on their α-amylase and α-glucosidase inhibitory activities.     

Antidiabetic potential and enzyme kinetics of benzothiazole derivatives and their non-bonded interactions with α-glucosidase and α-amylase

Benzothiazole derivatives were synthesized and their antidiabetic potential evaluated using α-glucosidase, α-amylase, non-enzymatic glycosylation of hemoglobin and advanced glycation end product inhibition assays. Compound 3l showed low IC₅₀ values of 0.31, 0.98, 0.59 and 0.19 mM in α-amylase, α-glucosidase, non-enzymatic glycosylation of hemoglobin and AGE inhibition assays, respectively, and outperformed the standard acarbose. Enzyme kinetic studies revealed that it has a K _i of 0.39 and 1.5 mM for α-amylase and α-glucosidase, respectively. The non-bonded interactions of 3l with α-amylase (3OLD) and α-glucosidase (2ZE0) showed that it binds in the active site pocket and is surrounded by residues Asp197, Glu233, Asp300 in 3OLD and Asp199, Glu256, Asp326 in 2ZE0.     

In-vitro α-amylase and α-glucosidase inhibitory activity of Adiantum caudatum Linn. and Celosia argentea Linn. extracts and fractions

Objective:

The objective of the present study was to provide an in-vitro evidence for the potential inhibitory activity of extracts and fractions of Adiantum caudatum Linn. and Celosia argentea Linn. on α-amylase and α-glucosidase enzymes.

Materials and Methods:

The plant extracts were prepared, first with cold maceration (70% v/v ethanol) and then by Soxhlation techniques (95% v/v ethanol). Subsequently, the combined extracts were subjected for fractionation. Different concentrations (0.1, 0.2, 0.3, 0.4, and 0.5 mg/ml) of extract and fractions were subjected to α-amylase and α-glucosidase inhibitory assay. The absorbance was measured at 540 and 405 nm using multiplate reader and the percentage of α- amylase and α- glucosidase inhibitory activity and IC₅₀ values of extract and fractions were calculated.

Results:

Fraction 2 of A. caudatum and fraction 4 of C. argentea has shown highest α-amylase and α-glucosidase inhibitory potential with IC₅₀ values of 0.241, 0.211 and 0.294, 0.249 mg/ml, respectively, which was comparable with acarbose (0.125 and 0.93 mg/ml). Whereas, extracts and remaining fractions of both the plants have shown lesser activity.

Conclusion:

The results of the present study indicate that, fraction 2 of A. caudatum, rich in triterpenoids and phenolics and fraction 4 of C. argentea, rich in flavonoids, are effective α- amylase and α- glucosidase inhibitors, which may be helpful to reduce the postprandial glucose levels. Hence, further studies may throw light on the antidiabetic potential of A. caudatum and C. argentea, especially in the management of type 2 diabetes.KEY WORDS: α- amylase, α-glucosidase, Mayurasikha, type 2 diabetes     

Effect of converting enzyme inhibition and angiotensin receptor blockade on the vasoconstriction mediated by α1 and α2 stimulation in pithed normotensive rats

Summary The effect of functional impairment of the renin-angiotensin system on the vasoconstriction mediated by postsynaptic ₁ and ₂-adrenoceptors in pithed normotensive rats was studied. Selective ₁-adrenoceptor stimulation was induced by intravenously administered cirazoline, whereas B-HT 920 was used as a selective agonists at ₂-adrenoceptors. The angiotensin converting enzyme was inhibited by intravenous treatment of the pithed rats with captopril, teprotide or enalapril. Blockade of angiotensin receptors was produced by intravenously applied [Sar¹ Ala⁸]angiotensin II (saralasin). Pretreatment with angiotensin converting enzyme inhibitors or with saralasin in doses which produced a maximal reduction in basal diastolic blood pressure, only slightly attenuated the hypertensive response to cirazoline. In contrast, these drugs provoked a most significant reduction of the ₂-adrenoceptor mediated vasoconstriction. Restoration of the basal diastolic blood pressure by intravenous infusion with angiotensin II or with vasopressin completely reversed the inhibitory effect of captopril on the vasopressor response to B-HT 920. One hour after bilateral nephrectomy, captopril still reduced the ₂-adrenoceptor mediated vasoconstriction. However, 18–24 h after bilateral nephrectomy, captopril had no additional inhibitory effect on the vasopressor response to selective ₂-adrenoceptor stimulation. It is concluded that in pithed normotensive rats the pressor response to ₂-adrenoceptor stimulation is significantly potentiated by endogenous angiotensin II, even at low circulating levels of the octapeptide. The modulatory action of angiotensin II on the -adrenoceptor mediated vasoconstriction probably represents an effect on the basal arteriolar muscular tone rather than a specific interaction.     

Evaluation of in silico,in vitro α-amylase inhibition potential and antidiabetic activity of Pterospermum acerifolium bark

Context: Pterospermum acerifolium (L.) Willd (Sterculiaceae) has been traditionally used in the treatment of diabetes mellitus but no scientific data has been published supporting the claimed ethnomedical use.

Objective: The present study was designed to estimate the in silico, in vitro α-amylase inhibition potential and anti-diabetic activity of Pterospermum acerifolium bark.

Materials and methods: In silico studies were performed between human pancreatic α-amylase (HPA) and β-sitosterol by using autodock 4.2 software. In vitro α-amylase inhibition study was carried out with 50% ethanol extract of the bark (PABEE) and its various fractions. The active ethyl acetate fraction (PABEF) was sub-fractionated into three fractions (PABE1, PABE2 and PABE3). Two doses (15 and 30?mg/kg) based on acute toxicity studies, of the above fractions were subjected to antidiabetic screening in vivo by STZ-nicotinamide induced type II diabetic rats.

Results: In silico studies showed the potent inhibition of β-sitosterol on human pancreatic amylase (HPA) with an estimated inhibition constant (K_i) of 269.35?nmol and two hydrogen bond interactions. PABEF showed marked α-amylase inhibition (69.94%) compared to other fractions. Diabetic rats treated with PABE3 (30?mg/kg) reduced the levels of fasting blood glucose, HbA1c, ALT, AST, ALP, triglycerides, total cholesterol, TBARS significantly (p?p?Conclusion: The present study confirmed the antihyperglycemic activity along with its status on hepatic biomarkers, antihyperlipidemic and antioxidant properties of Pterospermum acerifolium bark.     

Platycodi radix saponin inhibits α-glucosidase in vitro and modulates hepatic glucose-regulating enzyme activities in C57BL/KsJ-db/db mice

This study investigated anti-diabetic activity of a concentrated saponin fraction from Platycodi radix (SK1) in C57BL/KsJ-db/db mice and its underlying mechanism. Mice were fed diet with 0.5 % SK1 (w/w) for 6 weeks. SK1 significantly lowered the blood glucose and glycosylated hemoglobin levels and improved glucose and insulin tolerance. The plasma and pancreatic insulin and C-peptide levels and fecal cholesterol content were increased, whereas plasma urea nitrogen, free fatty acid and triglyceride levels were decreased by SK1 supplementation. Glucokinase (GK) activity in the liver was significantly higher in the SK1 group than the control group, whereas the glucose-6-phosphatase (G6Pase) activity was lower. SK1 significantly down-regulated GK mRNA expression compared to the control group but did not affect G6Pase and glucose transporter 2 mRNA. Phosphoenolpyruvate carboxykinase activity and mRNA levels did not differ between groups. SK1 also markedly inhibited the small intestinal disaccharidases activities compared to those of control db/db mice. Furthermore, SK1 was a more effective α-glucosidase inhibitor than acarbose in vitro. Overall, these findings suggest that SK1 is a potential glucose-lowering agent that functions via inhibition of carbohydrate digestive enzyme activities and modulation of glucose-regulating enzyme activities in db/db mice.     

Salivary α-amylase,serum albumin,and myoglobin protect against DNA-damaging activities of ingested dietary agents in vitro

Potent DNA-damaging activities were seen in vitro from dietary chemicals found in coffee, tea, and liquid smoke. A survey of tea varieties confirmed genotoxic activity to be widespread. Constituent pyrogallol-like polyphenols (PLPs) such as epigallocatechin-3-gallate (EGCG), pyrogallol, and gallic acid were proposed as a major source of DNA-damaging activities, inducing DNA double-strand breaks in the p53R assay, a well characterized assay sensitive to DNA strand breaks, and comet assay. Paradoxically, their consumption does not lead to the kind of widespread cellular toxicity and acute disease that might be expected from genotoxic exposure. Existing physiological mechanisms could limit DNA damage from dietary injurants. Serum albumin and salivary α-amylase are known to bind EGCG. Salivary α-amylase, serum albumin, and myoglobin, but not salivary proline-rich proteins, reduced damage from tea, coffee, and PLPs, but did not inhibit damage from the chemotherapeutics etoposide and camptothecin. This represents a novel function for saliva in addition to its known functions including protection against tannins. Cell populations administered repeated pyrogallol exposures had abatement of measured DNA damage by two weeks, indicating an innate cellular adaptation. We suggest that layers of physiological protections may exist toward natural dietary products to which animals have had high-level exposure over evolution.     

In vitro α-amylase and pancreatic lipase inhibitory activity of Cornus mas L. and Cornus alba L. fruit extracts

Less-common fruits from Cornus spp. (Cornaceae), also named dogwoods, have shown antidiabetic, antibacterial and anti-allergic properties and are thus considered a source of phytochemicals that are beneficial to human health. The study aimed to compare the chemical compositions of the aqueous and ethanolic extracts of lyophilized fresh-picked and commercially available dried fruits of Cornus mas (Cm, cornelian cherry) and Cornus alba (Ca) fruits using HPLC-DAD-MS/MS method. Simultaneously, the α-amylase and pancreatic lipase (PL) inhibitory activities of the prepared extracts were compared by in vitro fluorescence assay based on the kinetic hydrolysis of starch or oleate ester of 4-methylumbelliferone (MUO), respectively. Additionally, a bio-assay guided identification of compounds potentially responsible for the inhibition of pancreatic enzymes was performed. Iridoids (loganic acid, cornuside) and anthocyanins (pelargonidin 3-O-galactoside) were identified in the Cm fruit extracts. Flavonoids, such as quercetin and kaempferol derivatives, were detected in the Ca fruit extracts. The chromatographic separation of the constituents of Ca fruit provided a fraction containing phenolic acids derivatives, which inhibited PL activity by 69.9 ± 4.5% at a concentration of 7.5 μg·mL^?1. The IC₅₀ of hydroxytyrosol glucoside, isolated from the most active Ca fraction, was 0.99 ± 0.10 mg·mL^?1 indicating other constituents responsible for the fraction activity. The most active subfraction from Cm fruit (7.5 μg·mL^?1), which inhibited PL activity by 28.3 ± 1.5%, contained pelargonidin 3-O-galactoside. Loganic acid and cornuside in highly pure form did not inhibit lipase activity. The phytochemical constituents of Cm, and particularly of Ca fruit extracts, can inhibit pancreatic enzymes and thus might be considered effective preparations in the prevention and control of hyperlipidemia related diseases.     

Combination of α-glucosidase inhibitor and ribavirin for the treatment of dengue virus infection in vitro and in vivo

Cellular α-glucosidases I and II are enzymes that sequentially trim the three terminal glucoses in the N-linked oligosaccharides of viral envelope glycoproteins. This process is essential for the proper folding of viral glycoproteins and subsequent assembly of many enveloped viruses, including dengue virus (DENV). Imino sugars are substrate mimics of α-glucosidases I and II. In this report, we show that two oxygenated alkyl imino sugar derivatives, CM-9-78 and CM-10-18, are potent inhibitors of both α-glucosidases I and II in vitro and in treated animals, and efficiently inhibit DENV infection of cultured human cells. Pharmacokinetic studies reveal that both compounds are well tolerated at doses up to 100mg/kg in rats and have favorable pharmacokinetic properties and bioavailability in mice. Moreover, we showed that oral administration of either CM-9-78 or CM-10-18 reduces the peak viremia of DENV in mice. Interestingly, while treatment of DENV infected mice with ribavirin alone did not reduce the viremia, combination therapy of ribavirin with sub-effective dose of CM-10-18 demonstrated a significantly enhanced antiviral activity, as indicated by a profound reduction of the viremia. Our findings thus suggest that combination therapy of two broad-spectrum antiviral agents may provide a practically useful approach for the treatment of DENV infection.     

An in vitro reconstitution system to address the mechanism of the vascular expression of the bradykinin B₁ receptor in response to angiotensin converting enzyme inhibition

The expression of the bradykinin (BK) B? receptor (B?R), lacking in normal vascular tissues, is induced following innate immune system activation and chronic blockade of angiotensin converting enzyme (ACE). To identify cytokine-dependent or -independent mechanisms for the latter phenomenon, the ACE inhibitor enalaprilat and several peptides potentiated in vivo by ACE blockade were applied either directly to human umbilical artery smooth muscle cells (hUA-SMCs) or to differentiated monoblastoid U937 cells to produce a conditioned medium (CM) that was later transferred to hUA-SMCs. A phagocyte stimulant, lipopolysaccharide, did not upregulate B?R, measured using [3H]Lys-des-Arg?-BK binding, or translocate NF-κB to the nuclei if applied directly to the hUA-SMCs. However, the CM of lipopolysaccharide-stimulated U937 cells was active in these respects (effects inhibited by etanercept and correlated to TNF-α presence in the CM). A peptidase-resistant B?R agonist had no significant direct or indirect acute effect (4h) on B?R expression, but repeated hUA-SMC stimulations over 40 h were stimulatory in the absence of NF-κB activation. Other peptides regulated by ACE or enalaprilat did not directly or indirectly stimulate B?R expression. The reconstitution system supports the rapid cytokine-dependent vascular induction of B?Rs and a slow "autoregulatory" one potentially relevant for the ACE blockade effect.     

The effect of angiotensin converting enzyme inhibitors (ACE-I) and selective β1-antagonists on bronchial reactivity and the cough reflex in man

Summary The non-specific bronchial reactivity and cough threshold of hypertensive patients on an ACE-I monotherapy regimen (either captopril or enalapril), a ₁-antagonist monotherapy regimen (either atenolol or metoprolol) or a combination of an ACE-I with a ₁-antagonist were determined in the present study. Forty-six hypertensives who were on these medications performed a histamine inhalation test (to assess bronchial reactivity) and a further 36 of these individuals participated in the citric acid test (to assess cough threshold). A control cohort consisting of 25 age-matched, drug-free subjects also performed the citric acid test.The incidence of bronchial hyperreactivity was not significantly different between the ACE-I monotherapy regimen and the ₁-antagonist monotherapy regimen (Chi-squared =0.248). However, when the monotherapy regimens were pooled and compared with the ACE-I and ₁-antagonist combination regimen, the combination regimen was found to be associated with a significantly higher incidence of bronchial hyperreactivity (Chi-squared =6.69). No difference was observed between the age-matched controls and the hypertensive patients in terms of their cough threshold.     

Partial characterization of β-glucosidase, β-xylosidase,and α-l-arabinofuranosidase from Jiangella alba DSM 45237 and their potential in lignocellulose-based biorefining

Jiangella alba DSM 45237 exhibited excellent extracellular β-glucosidase (1.03 ± 0.09 U/mL), β-xylosidase (16.29 ± 0.23 U/mL), and α-l-arabinofuranosidase (7.00 ± 0.09 U/mL) production in the growth media containing 15 g/L wheat straw pretreated with NaOH. The optimum temperature was 40 °C for β-glucosidase and β-xylosidase, whereas it was 50 °C for α-l-arabinofuranosidase. Among them, α-l-arabinofuranosidase was relatively stable at 60 and 70 °C. Enzymes showed maximum activity at pH 8.0. Enzymes, particularly β-glucosidase and α-l-arabinofuranosidase, were able to tolerate NaCl up to a final concentration of 12% (v/w). Among solvents, only ethanol and methanol increased the β-glucosidase activity. The majority of solvents did not significantly affect β-xylosidase activity but increased α-l-arabinofuranosidase activity. Except for phenol, other lignocellulose-derived compounds did not cause a significant activity loss in enzymes. Some of them, such as vanillic acid and acetic acid, have even increased the activity of enzymes. Hydrolysis of pretreated wheat straw using the crude enzyme from J. alba DSM 45237 released 160.9 mg/gds reducing sugars. Analysis of hydrolysis products with thin layer chromatography (TLC) showed that major products were 5C sugars. This is the first report related to the characterization of β-glucosidase, β-xylosidase, and α-l-arabinofuranosidase from J.alba DSM 45237 to date.     

Identification of highly potent α-glucosidase inhibitory and antioxidant constituents from Zizyphus rugosa bark: enzyme kinetic and molecular docking studies with active metabolites

Context: Previous studies have shown that extracts of Zizyphus rugosa Lam. (Rhamnaceae) bark contained phytoconstituents with antidiabetic potential to lower blood glucose levels in diabetic rats. However, there has been no report on the active compounds in this plant as potential antidiabetic inhibitors.

Objective: We evaluated the α-glucosidase inhibitory and antioxidant activities of Z. rugosa extract. Moreover, the active phytochemical constituents were isolated and characterized.

Materials and methods: The α-glucosidase inhibition of crude ethanol extract obtained from the bark of Z. rugosa was assayed as well as the antioxidant activity. Active compounds (1–6) were isolated, the structures were determined, and derivatives (2a–2?l) were prepared. All compounds were tested for their α-glucosidase inhibitory (yeast and rat intestine) and antioxidant (DPPH) activities.

Results: The active α-glucosidase inhibitors (1–6) were isolated from Z. rugosa bark and 12 derivatives (2a–2?l) were prepared. Compound 2 showed the most powerful yeast α-glucosidase inhibitory activity (IC₅₀ 16.3?μM), while compounds 3 and 4 display only weak inhibition toward rat intestinal α-glucosidase. Moreover, compound 6 showed the most potent antioxidant activity (IC₅₀ 42.8?μM). The molecular docking results highlighted the role of the carboxyl moiety of 2 for yeast α-glucosidase inhibition through H-bonding.

Discussion and conclusions: These results suggest the potential of Z. rugosa bark for future application in the treatment of diabetes and active compounds 1 and 2 have emerged as promising molecules for therapy.     

Xanthones as potential α-glucosidase non-competition inhibitors: Synthesis,inhibitory activities,and in silico studies

α-glucosidase inhibitors (AGIs) were commonly used in clinical for the treatment of type 2 diabetes. Xanthones were naturally occurring antioxidants, and they may also be potential AGIs. In this study, eleven 1,6- and 1,3-substituted xanthone compounds were designed and synthesized, of which four were new compounds. Their α-glucosidase inhibitory activities in vitro and in silico were evaluated. Five xanthone compounds with higher activity than acarbose were screened out, and the xanthones substituted at the 1,6-positions were more likely to be potential α-glucosidase non-competitive inhibitors. The binding mode of xanthones with α-glucosidase was further studied by molecular docking method, and the results showed that the inhibitory effect of non-competitive inhibitors on site 1 of α-glucosidase may be related to the hydrogen bonds formed by the compounds with amino acid residues ASN165, HIS209, TRY207, ASP243, and SER104. This study provided a theoretical basis of the rapid discovery and structural modification of non-competitive xanthone inhibitors of α-glucosidase.     

Comparison of the intestinal absorption and bioavailability of γ-tocotrienol and α-tocopherol: in vitro, in situ and in vivo studies

The aim of this work was to compare the intestinal absorption kinetics and the bioavailability of γ-tocotrienol (γ-T3) and α-tocopherol (α-Tph) administered separately as oil solutions to rats in vivo. Also, to explain the significant difference in the oral bioavailability of the compounds: (1) the release profiles using the dynamic in vitro lipolysis model, (2) the intestinal permeability and (3) carrier-mediated uptake by Niemann-Pick C1-like 1 (NPC1L1) transporter were examined. Absolute bioavailability studies were conducted after oral administration of γ-T3 or α-Tph prepared in corn oil to rats. In situ rat intestinal perfusion with ezetimibe (a NPC1L1 inhibitor) was performed to compare intestinal permeability. The in vitro interaction kinetics with NPC1L1 was examined in NPC1L1 transfected cells. While the in vitro release studies demonstrated a significantly higher release rate of γ-T3 in the aqueous phase, the oral bioavailability of α-Tph (36%) was significantly higher than γ-T3 (9%). Consequent in situ studies revealed significantly higher intestinal permeability for α-Tph compared with γ-T3 in rats. Moreover, the NPC1L1 kinetic studies demonstrated higher Vmax and Km values for α-Tph compared with γ-T3. Collectively, these results indicate that intestinal permeability is the main contributing factor for the higher bioavailability of α-Tph. Also, these results emphasize the potentially important role of intestinal permeability in the bioavailability of γ-T3, suggesting that enhancing its permeability would increase its oral bioavailability.