Inhibit Α-glucosidase Enzyme Research Articles

Experimental Validation of Antiobesogenic and Osteoprotective Efficacy of Ginsenoside CK via Targeting Lipid and Atherosclerosis Pathways.

The present study explored the possible antiobesogenic and osteoprotective properties of the gut metabolite ginsenoside CK to clarify its influence on lipid and atherosclerosis pathways, thereby validating previously published hypotheses. These hypotheses were validated by harvesting and cultivating 3T3-L1 and MC3T3-E1 in adipogenic and osteogenic media with varying concentrations of CK. We assessed the differentiation of adipocytes and osteoblasts in these cell lines by applying the most effective doses of CK that we initially selected. Using 3T3-L1 adipocytes in vitro assessments, CK could effectively decrease intracellular lipid accumulation, inhibit α-glucosidase enzyme, increase 2-NBDG glucose uptake, reduce inflammation-associated cytokines (TNFα, and IL-6), adipogenic regulatory genes (PPARγ, FAS, C/EBPα), lipogenic gene LPL, and increase the expression of thermogenic gene UCP1. Additionally, CK treatment induced osteoblast development in MC3T3-E1 cells as shown by increased mineralization and calcium distribution, collagen content, alkaline phosphatase activity, and decreased inflammatory cytokines TNFα, and IL-6 and increased the regulated expressions of osteogenic genes including Runx2, ALP, BGLAP, OCN, and Col1a1. Significantly, as a major inhibitory regulator, the TP53 gene was down-regulated in both 3T3-L1 and MC3T3E1 cells after the treatment of CK. These encouraging results demonstrate the possible use of CK as an innovative treatment for controlling obesity and osteoporosis, targeting the underlying mechanisms of obesogenic and bone loss. Further studies are necessary to explore the clinical implications of these results and the potential of CK in future treatment strategies. This research highlights the promise of CK in addressing significant health issues.

A comparative study of in vivo toxicity in zebrafish embryos synthesized CuO nanoparticles characterized from Salacia reticulata.

The Salacia reticulata, a medicinal woody climbing shrub, was utilized for our study, the green synthesis of CuO nanoparticles, which were analyzed through SEM, EDX, FTIR, XRD, and UV‒Vis spectroscopy. This study assessed the toxicity to zebrafish embryos and explored the antibacterial, cytotoxic, antidiabetic, and anti-inflammatory properties of the synthesized nanoparticles. In results, the UV absorption of the CuO NPs showed that the intensity of nanoparticle green colloidal suspension changed from blue to green, which also confirmed that the spectrum of the green CuO NPs changed from colorless to black. in FT-IR and XRD spectral analysis to identify functional groups and determine the particle size of CuO NPs prepared by green and chemical methods. Its showed that CuO NPs (green) had a size of approximately 42.2nm, while CuO NPs (chemical) had a size of approximately 84nm. The morphology of these NPs was analyzed using SEM-EDX. Compared with their chemically prepared counterparts, the green-synthesized CuO nanoparticles demonstrated superior dispersion. Additionally, both green and chemical CuO nanoparticles at a concentration of 200 µL/mL caused developmental anomalies and increased mortality in zebrafish embryos and larvae. The green and chemical CuO NPs inhibited α-glucosidase enzyme activity at concentrations between 10 and 50 µL/mL, with IC50 values of 22 µL/mL and 26 µL/mL, respectively. The extract exhibited anti-inflammatory activity, with IC50 values of 274 and 109 µL/mL. The authors concluded that this green nanoparticle method has potential as a more eco-friendly and cost-effective alternative to traditional synthetic methods. NPs are widely used in human contact fields (medicine and agriculture), hence synthesis methods that do not involve toxic substances are becoming increasingly important.

Two tetrahydroxyterpenoids and a flavonoid from Xylocarpus moluccensis M.Roem. and their α-glucosidase inhibitory and antioxidant capacity

Context: Scientific verification of the anti-hyperglycemic potential of Kayu sarampa (Xylocarpus moluccensis), which is popularly used for diabetic medication in North Sulawesi, Indonesia, is strongly important to conduct to avoid inappropriate medication that might cause worse conditions. Aims: To investigate the anti-hyperglycemic potential of X. moluccensis stem bark ethyl acetate extract and isolated compounds through the α-glucosidase enzyme inhibitory and antioxidant capacity determination. Methods: The active compound was isolated from ethyl acetate extract of X. moluccensis stem bark. The structures of those compounds were elucidated by infrared spectroscopy, liquid chromatography–mass spectrometry, and nuclear magnetic resonance spectroscopies. To discover the anti-hyperglycemic potency, α-glucosidase enzyme inhibition assay, antioxidant assay (DPPH and FRAP), and in silico study were performed. Results: Three isolated compounds were obtained and characterized as two tetrahydroxyterpenoids compounds, namely xyloccensin E (1) and ruageanin D (2), and one flavonoid compound, namely 3,5,7,3ʹ,4ʹ-pentahidroxyflavan (catechin) (3). Compounds 1 and 3 inhibited the α-glucosidase enzyme with IC50 values of 118.60 and 55.19 µg/mL, respectively, with a competitive inhibition mechanism. This is also in line with in silico findings, and both compounds showed good binding affinity of α-glucosidase protein, which indicated their anti-hyperglycemic activity potential by inhibiting α-glucosidase enzyme. Moreover, compounds 1 and 3 showed antioxidant capacity through the DPPH method with an IC50 value of 54.69 and 2.87 µg/mL. In addition, 100 µg/mL of compounds 1 and 3 also exhibited antioxidant capacity through the FRAP method with values of 66.35 and 213.82 µmol Fe2+/g, respectively. Conclusions: The X. moluccensis stem bark ethyl acetate extract, and isolated compounds exhibit α-glucosidase enzyme inhibitory activity and antioxidant capacity, which confirms its potency as an alternative medication for hyperglycemia issues.

Quinoline-based Schiff bases as possible antidiabetic agents: ligand-based pharmacophore modeling, 3D QSAR, docking, and molecular dynamics simulations study.

α-Glucosidase enzyme inhibition is a legitimate approach to combat type 2 diabetes mellitus as it manages to control postprandial hyperglycemia. In this pursuit, a literature search identified quinoline-based molecules as potential α-glucosidase inhibitors. Thus our intended approach is to identify pharmacophoric features responsible for the α-glucosidase inhibition. This was achieved by performing, ligand-based pharmacophore modeling, 3D QSAR model development, pharmacophore-based screening of a rationally designed quinoline-based benzohydrazide Schiff base library, identifying, synthesizing and characterizing molecules (6a-6j) by IR, (1H and 13C) NMR, and mass studies. Further, these molecules were evaluated for α-glucosidase and α-amylase inhibitory potential. Compound 6c was found to inhibit α-glucosidase enzyme with an IC50 value of 12.95 ± 2.35 μM. Similarly, compound 6b was found to have an IC50 value of 19.37 ± 0.96 μM as compared to acarbose (IC50: 32.63 ± 1.07 μM); the inhibitory kinetics of compounds 6b and 6c revealed a competitive type of inhibition; the inhibitory effect can be attributed to its mapped pharmacophoric feature and model validation with a survival score of 5.0697 and vector score of 0.9552. The QSAR model showed a strong correlation with an R 2 value of 0.96. All the compounds (6a-6j) showed no toxicity in L929 cell lines by the MTT assay method. Further, the binding orientation and stability of the molecules were assessed using molecular docking studies and MD trajectory analysis. The energy profile of the molecules with protein as a complex and molecules alone was evaluated using MM/GBSA and DFT calculations, respectively; finally, the pharmacokinetic profile was computed using ADMET analysis.

Salazinic Acid and Norlobaridone from the Lichen Hypotrachyna cirrhata: Antioxidant Activity, α-Glucosidase Inhibitory and Molecular Docking Studies

The present study was intended for the identification of secondary metabolites in acetone extract of the lichen Hypotrachyna cirrhata using UPLC-ESI-QToF-MS/MS and the detection of bioactive compounds. This study led to the identification of 22 metabolites based on their MS/MS spectra, accurate molecular masses, molecular formula from a comparison of the literature database (DNP), and fragmentation patterns. In addition, potent antioxidant and α-glucosidase inhibitory potentials of acetone extract of H. cirrhata motivated us to isolate 10 metabolites, which were characterized as salazinic acid (11), norlobaridone (12), atranorin (13), lecanoric acid (14), lichesterinic acid (15), protolichesterinic acid (16), methyl hematommate (17), iso-rhizonic acid (18), atranol (19), and methylatratate (20) based on their spectral data. All these isolates were assessed for their free radicals scavenging, radical-induced DNA damage, and intestinal α-glucosidase inhibitory activities. The results indicated that norlobaridone (12), lecanoric acid (14), methyl hematommate (17), and atranol (19) showed potent antioxidant activity, while depsidones (salazinic acid (11), norlobaridone (12)) and a monophenolic compound (iso-rhizonic acid, (18)) displayed significant intestinal α-glucosidase inhibitory activities (p < 0.001), which is comparable to standard acarbose. These results were further correlated with molecular docking studies, which indicated that the alkyl chain of norlobaridione (12) is hooked into the finger-like cavity of the allosteric pocket; moreover, it also established Van der Waals interactions with hydrophobic residues of the allosteric pocket. Thus, the potency of norlobaridone to inhibit α-glucosidase enzyme might be associated with its allosteric binding. Also, MM-GBSA (Molecular Mechanics-Generalized Born Surface Area) binding free energies of salazinic acid (11) and norlobaridone (12) were superior to acarbose and may have contributed to their high activity compared to acarbose.

Investigation of extraction conditions and evaluation of the ability of antioxidants and lowering blood glucose levels of the Ensete glaucum extract

Diabetes is a type of metabolic disorder, which is the cause of many dangerous complications. Ensete glaucum (Musaceae family) has active ingredients with antioxidant and hypoglycemic characteristics in some parts of the plant. This study investigates the ability to reduce blood sugar based on the inhibition of α-amylase and α-glucosidase enzymes of Ensete glaucum stem extract. The results indicated that 70% ethanol, a material ratio of 1/30, and a temperature of 65oC for 360 minutes are the optimal conditions for the extraction process. Sonication has an extraction efficiency that is 1.8 times greater than that of a thermostatic bath or shaker. With the above conditions, the total polyphenol contents of the upper and the lower stem samples combined with sonication are higher than those without sonication. The ability to capture 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radicals of the extract used with sonication in the upper stem is four times higher than without sonication. In addition, the presence of sonication increases the capacity to inhibit the α-amylase enzyme (IC50 of the upper stem is 29.94 g/mL, the lower stem is 16.42 g/mL), compared to the absence of sonication (IC50 of the upper stem is 36 g/mL, the lower stem is 26.72 g/mL). Similar to the ability to inhibit α-glucosidase enzyme when using sonication (IC50 of the upper stem is 71.04 µg/mL, the lower stem is 91.91 µg/mL) is higher than not using sonication (IC50 of the upper stem is 142.99 µg/mL, the lower stem is 129.88 µg/mL). In general, the inhibition of α-amylase enzyme was higher than α–glucosidase enzyme in all extracts. In addition, the presence of sonication increased the polyphenol content, DPPH free radical scavenging, and hypoglycemic capacity of Ensete glaucum stem extract.

Novel sulfonamide-functionalized arylidene indolones as potent α-glucosidase inhibitors: Synthesis, characterization, and in vitro and in silico studies

Novel sulfonamide-functionalized arylidene indolones as potent α-glucosidase inhibitors: Synthesis, characterization, and in vitro and in silico studies

The Synthesis of Schiff bases and new secondary amine derivatives of p-vanillin and evaluation of their neuroprotective, antidiabetic, antidepressant and antioxidant potentials

• New Schiff bases and secondary amines derivatives of p -vanillin reacting with dopamine, histamine, 2-aminophenol, 4-aminophenol and 4-aminomorpholine were synthesized. • Antidiabetic, neuroprotective, antidepressant and antioxidant properties of the synthesized molecules were determined for the first time. • Compounds 1 and 3 were found to be potential neuroprotective agents inhibiting potently AChE and BChE enzymes. • Although all synthesized molecules acted as α-glucosidase inhibitor, compound 1 was found to be the strongest inhibitor among synthesized molecules. • All of molecules possess strong antioxidant potentials by strongly scavenging ABTS and DPPH radicals and by exhibiting strong reducing power. • Among the molecules, compound 1 stands out as a target molecule for in vivo as well as clinical studies due to its potent neuroprotective, antidiabetic and antioxidant potentials. In the current study, five Schiff base derivatives coded as VDOPL ( 1 ), VHISL ( 2 ), V2-AFL ( 3 ), V4-AFL ( 4 ) and VAML ( 5 ) from p -vanillin were synthesized with dopamine, histamine, 2-aminophenol, 4-aminophenol and 4-aminomorpholine. Afterwards, these Schiff bases were reduced with NaBH 4 to produce secondary amines coded as VDOPA ( 6 ), V2-AFA ( 7 ), V4-AFA ( 8 ) and VAMA ( 9 ). The chemical structures of the synthesized molecules were characterized by UV-Visible, FTIR, 1 H-NMR, 13 C-NMR, DEPT, APT, 1 H, 1 H-COSY, HMQC and HMBC methods. The enzyme inhibitory properties of p -vanillin, the primary amines, the Schiff bases and novel secondary amine derivatives on cholinesterase's (AChE and BChE) and on α-glycosidase and α-amylase enzyme activities were evaluated for the first time to determine their neuroprotective and antidiabetic effects, respectively. The antioxidant potentials of all molecules were also investigated by testing the ABTS and DPPH radical scavenging activities and reducing power. The neuroprotective, antidiabetic and antioxidant potentials of the molecules were also compared with the commercial drugs, neostigmine and galantamine (anticholinesterases), acarbose (antidiabetic), BHA and Trolox (antioxidants), respectively. The results of the molecules’ inhibitory effects on the AChE indicated that the neuroprotective effects of all molecules, except for VDOPL ( 1 ) are much weaker than the anticholinesterases, neostigmine and galantamine. VDOPL ( 1 ) demonstrated a potent inhibitory effect on the AChE with IC 50 =1.53 mg/mL. Whereas, it was proved that all of the tested molecules showed the stronger inhibitory effects against BChE enzyme than AChE enzyme, and VDOPL ( 1 ) and V2-AFL ( 3 ) were found to be the most effective inhibitors against both AChE and BChE enzymes among the tested molecules. The results on the antidiabetic potentials of the molecules showed that all synthesized molecules except V2-AFL ( 3 ) and VAML ( 5 ) inhibited α-glucosidase enzyme more potently than the antidiabetic agent, acarbose. Among the tested molecules, 4-aminophenol (IC 50 =0.44 mg/mL) and VDOPL ( 1 ) (IC 50 =0.45 mg/mL) were found to be the strongest inhibitors on α-glycosidase activity. However, all the tested molecules demonstrated the weaker inhibition effects as compared with the inhibition effect of the acarbose against α-amylase. Moreover, all of the tested molecules exhibited strong antioxidant potentials. Based on the current results, VDOPL ( 1 ) stands out as a target molecule for in vivo as well as clinical studies due to its potent neuroprotective, antidiabetic and antioxidant potentials. In addition, the antidepressant properties of p -vanillin, the Schiff bases and the secondary amines were tested for the first time against the MAO-A enzyme and their antidepressant properties were compared with the MAO inhibitor, clorgiline. The current results showed that p -vanillin (IC 50 =0.72 mg/mL), V2-AFL ( 3 ) (IC 50 =0.71 mg/mL), V2-AFA ( 7 ) (IC 50 =1.22 mg/mL) and V4-AFA ( 8 ) (IC 50 =2.36 mg/mL) are the potential antidepressant agents, despite the fact that the antidepressant effects were lower than that of clorgiline (IC 50 =0.34 mg/mL). However, the in vivo antidepressant properties, safeties and toxicities of the molecules should be investigated with further studies.

Hypoglycemic effect of leaf extract of Pseuderanthemum crenulatum leaves in an alloxan-induced diabetic mice

In this study, the hypoglycaemic effects of ethanol extracts from Pseuderanthemum crenulatum leaves were investigated. The evaluated trials included: in vitroα-glucosidase inhibitory activity; oral glucose tolerance test in normoglycemic mice; hypoglycemia in an alloxan-induced diabetic mice model, and oral toxicity assay. The results showed that the ethanol extract of P. crenulatumleaves was able to inhibit α-glucosidase enzyme at IC50=66.01 μg/ml, 1.8 times higher than acarbose control (IC50 was 122.2 μg/ml). After 21 days of using leaf extract of P. crenulatum (1 g/kg) to treat diabetic mice, the blood glucose was reduced by 42.02%. This result was equivalent to gliclazide (10 mg/kg) which reduced the blood glucose of diabetic mice by 41.78%. The oral toxicity test results at a dose of 5 g/kg equivalent to 357 g of fresh leaf/kg after 72 hours was not exhibited acute oral toxicity in mice. In summary, there is a need for more studies on the ability of P. crenulatum leaves to treat diabetes.

α- Glucosidase Inhibitory and Antioxidant Activities of Moluccella aucheri (Boiss.) Scheen Extracts

Background & Objective: α-Glucosidase is one of the main enzymes in the intestinal absorption of carbohydrates. Inhibition of this enzyme can improve postprandial hyperglycemia in diabetic patients. Also, antioxidants can ameliorate diabetes complications resulted from oxidative stress. In this study α-glucosidase inhibition, antioxidant activity and total phenol content of different extracts and obtained fractions of Moluccella aucheri have been evaluated. Materials & Methods: The ethanol extract of aerial parts of M. aucheri was fractionated using liquid extraction method with petroleum ether, dichloromethane and ethyl acetate, respectively. The extracts and the resulting fractions of M. aucheri were tested against α-glucosidase enzyme from yeast using an in vitro colorimetric model at λ 405 nm. Antioxidant activity was assessed using two different methods, ferric reducing antioxidant power (FRAP) and the scavenging activity of DPPH radicals’ methods. Results: The screening results indicated that the antioxidant activity and total phenolic content of the methanol extract were potentially higher than ethanol extract, while the ethanol extract inhibited α-glucosidase enzyme to a greater extent. Ethyl acetate fraction illustrated potentially the highest antioxidant activity and phenolic content, but its inhibition activity against α-glucosidase was placed after the petroleum ether fraction. Two previously isolated methoxy flavones; genkwanin, 5-hydroxyl-7, 4'-dimethoxyflavone inhibited the α-glucosidase enzyme strongly. Conclusion: Since the ethyl acetate extract has both considerable antioxidant activity and α-glucosidase inhibitory activity, it may be considered as a potential crude drug for diabetes.

Potential Mechanisms Involved in the Protective Effect of Dicaffeoylquinic Acids from Artemisia annua L. Leaves against Diabetes and Its Complications.

Diabetes mellitus is a chronic disease affecting the globe and its incidence is increasing pandemically. The use of plant-derived natural products for diabetes management is of great interest. Polar fraction of Artemisia annua L. leaves has shown antidiabetic activity in vivo. In the present study, three major compounds were isolated from this polar fraction; namely, 3,5-dicaffeoylquinic acid (1); 4,5-dicaffeoylquinic acid (2), and 3,4- dicaffeoylquinic acid methyl ester (3), using VLC-RP-18 and HPLC techniques. The potential protective effects of these compounds against diabetes and its complications were investigated by employing various in vitro enzyme inhibition assays. Furthermore, their antioxidant and wound healing effectiveness were evaluated. Results declared that these dicaffeoylquinic acids greatly inhibited DPPIV enzyme while moderately inhibited α-glucosidase enzyme, where compounds 1 and 3 displayed the most prominent effects. In addition, compound 3 showed pronounced inhibition of α-amylase enzyme. Moreover, these compounds markedly inhibited aldose reductase enzyme and exerted powerful antioxidant effects, among which compound 3 exhibited the highest activity implying a notable potentiality in impeding diabetes complications. Interestingly, compounds 2 and 3 moderately accelerated scratch wound healing. Our findings suggest that these dicaffeoylquinic acids can be promising therapeutic agents for managing diabetes and its complications.

Protective effect of D-(-)-quinic acid as food supplement in modulating AMP-activated protein kinase signalling pathway activation in HFD induced obesity.

Dietary quinic acid given as the nutritional supplement, which may leads to tryptophan and nicotinamide production in the intestinal tract and NAD+ precursor which can prevent from the negative consequences of high fat diet (HFD) consumption. The present study was designed to assess in vivo and in vitro effect of D-(-)-Quinic acid in high-fat diet induced hyperlipidemia in mice. Thirty six albino mice were randomly divided in six groups and each group had six mice. Group I, controlled mice given normal pellet diet, Group-II mice, administered with high fat diet (HFD), Group-III mice given standard drug, Atorvastatin (20mg/kg, p.o.) along with HFD to mice and Group IV, V and VI mice received D-(-)-Quinic acid at a dose of 75, 150 and 300mg/kg, respectively in separate group along with HFD to mice. After completion of trial (49days) the animals were sacrificed and evaluated for body weight, organ fat pad weight, and changes in weight of liver, heart and kidney and also for biochemical parameters, expression of adipogenic and inflammation markers in adipose tissues, and histology examination of liver tissue. In vitro testing results showed, D-(-)-Quinic acid potentially inhibit α-glucosidase enzyme activity as compared to acarbose. The D-(-)-Quinic acid showed significant hypolipidemic activity by decreasing the increased level of cholesterol, triglyceride level, LDL, VLDL and other hepatic parameters like SGOT and SGPT in serum. D-(-)-Quinic acid reduces the mRNA expression level of PPAR-γ2, TNF-α, IL-1β and IL-6 in adipose tissue in hyperlipidemic mice.

Poly(vinyl alcohol)-tannic Acid Cryogel Matrix as Antioxidant and Antibacterial Material.

The biocompatible, viscoelastic properties of poly(vinyl alcohol) (PVA) in combination with the antimicrobial and antioxidant natural polyphenolic, tannic acid (TA), and the natural flavonoid and antioxidant curcumin (Cur), were used in the preparation of PVA:TA and PVA:TA:Cur cryogel composites using cryotropic gelation to combine the individually beneficial properties. The effect of TA content on the antioxidant and antimicrobial activities of PVA:TA cryogel composites and the antioxidant activities of PVA:TA:Cur cryogel composites was determined using Trolox equivalent antioxidant capacity (TEAC) and total phenol content (TPC) assays, and were compared. The PVA:TA:Cur cryogel composite showed the highest antioxidant activity, with a TEAC value of 2.10 ± 0.24 and a TPC value of 293 ± 12.00. The antibacterial capacity of the PVA:TA and PVA:TA:Cur 1:1:0.1 cryogel composites was examined against two different species of bacteria, E. coli and S. aureus. It was found that the minimum inhibition concentration (MIC) value of the PVA:TA:Cur 1:1:0.1 cryogel composites varied between 5 and 10 mg/mL based on the type of microorganism, and the minimum bactericidal concentration (MBC) value was 20 mg/mL irrespective of the type of microorganism. Furthermore, the hemocompatibility of the PVA:TA cryogel composites was evaluated by examining their hemolytic and coagulation behaviors. PVA:TA 1:1 cryogels with a value of 95.7% revealed the highest blood clotting index value amongst all of the synthesized cryogels, signifying the potential for blood contacting applications. The release of TA and Cur from the cryogel composites was quantified at different pH conditions, i.e., 1.0, 7.4, and 9.0, and additionally in ethanol (EtOH) and an ethanol–water (EtOH:Wat) mixture. The solution released from the PVA:TA cryogels in PBS was tested for inhibition capability against α-glucosidase (E.C. 3.2.1.20). Concentration-dependent enzyme inhibition was observed, and 70 µL of 83 µg/mL PVA:TA (1:1) cryogel in PBS inhibited α-glucosidase enzyme solution of 0.03 unit/mL in 70 µL by 81.75 ± 0.96%.

Sweet cherry phenolics revealed to be promising agents in inhibiting P‐glycoprotein activity and increasing cellular viability under oxidative stress conditions: in vitro and in silico study

This study aimed to explore the total phenolic and anthocyanin content (TPC and TAC, respectively), and the biological potential of Portuguese sweet cherry cultivars. The TPC and TAC values ranged between 72.9 and 493.6 gallic acid equivalents per 100g fresh weight (fw), and from 1.0 to 179.1 cyanidin 3-O-rutinoside equivalents per 100g fw, respectively. Cristalina total extract was the most effective in capturing DPPH reactive species, whereas the colored fraction and the total extract of Saco cultivar were the most efficient in scavenging ferric and peroxide species. Celeste total extract was the most effective in inhibiting α-glucosidase enzyme. Phenolic-rich extracts and standard phenolics also revealed ability to interfere with the P-gp activity on MDCK-II and MDCK-MDR1 cells and to increase cellular viability under conditions of oxidative stress. Computational studies were performed to evaluate the interaction between phenolics and the P-gp activity. This study revealed that cherry extracts and their phenolic compounds present notable biological properties, encouraging the development of cherry-based dietary and medicinal supplements. PRACTICAL APPLICATION: The interest in phenolic-rich sources has increased significantly in recent years, given their capacity to prevent the development of chronic disorders, such as cancer. Recent evidence suggests that phenolic compounds can act as P-glycoprotein (P-gp) inhibitors, an important drug efflux transporter, preventing multidrug resistance, and thus, enhancing the therapeutic efficacy of some drugs in certain target cells. Our results indicate that enriched-fractions from sweet cherries can effectively interfere with the P-gp activity on MDCK-II and MDCK-MDR1 cells and protect against oxidative damage.

Bioactive stigmastadienone from Isodon rugosus as potential anticholinesterase, α-glucosidase and COX/LOX inhibitor: In-vitro and molecular docking studies

Natural product is a well-known source of bioactive compounds. Herein, a steroidal compound stigmasta-7,22-diene-3-one (stigmastadienone) has been isolated from Isodon rugosus. The potency of isolated compound has been tested for several in-vitro targets. The acetyl and butyrylcholinesterase assays were performed using Ellman's procedure. For the in-vitro antidiabetic potential, α-glucosidase inhibitory assay was performed. Similarly, the cyclo and lipoxygenase pathways were studied to find its potential role in the management of inflammation and analgesia. The 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and hydrogen peroxide (H2O2) assays were performed for the antioxidant potentials. Docking studies were performed against acetylcholinesterase, cyclooxygenase and lipoxygenase targets. In anticholinesterase assays, stigmastadienone exhibited half-maximal inhibitory concentration (IC50) values of 13.52 and 11.53μg/ml for acetyl and butyrylcholinesterase respectively. The observed IC50 values for that of galantamine were 6.07 and 4.42μg/ml for acety and butyrylcholinesterase respectively. In inhibiting α-glucosidase enzyme, the compound showed mediocre IC50 of 109.40μg/ml compared to the standard acarbose (7.60μg/ml). The stigmastadienone proved to be an excellent inhibitor of cyclooxygenase 2 (COX-2) and 5-lipoxygenase (5-LOX) attaining IC50 values of 4.72 and 3.36μg/ml respectively. The standard drugs IC50 values for COX-2 (celecoxib) and 5-LOX (montelukast) were 3.81 and 2.74μg/ml respectively. The enzymatic activities of stigmastadienone were also supplemented with antioxidant results, specifically it was more dominant against DPPH and ABTS free radicals. Docking studies showed that only the carbonyl oxygen is able to form hydrogen bond interaction with the residues. In conclusions, the stigmastadienone has been isolated from Isodon rugosus for the first time. Moreover, the compound has been evaluated for several biochemical pathways which suggest its pharmacological role on the explored targets.

Amelioration of Diabetes mellitus by modulation of GLP-1 via targeting alpha-glucosidase using Acacia tortilis polysaccharide in Streptozotocin-Nicotinamide induced diabetes in rats

BackgroundPolysaccharides decrease the glucose level by inhibiting α-glucosidase enzyme which further increases the level of GLP-1 (Glucagon-like peptide 1) to increase the insulin level as per earlier reports.ObjectiveSimilar hypothesis was designed in present study to investigate the α-glucosidase enzyme inhibition and involvement of GLP-1 in antidiabetic mechanism of Acacia tortilis polysaccharides (AEATP) in diabetic rats. Isolated polysaccharides were analyzed for their chemical nature by using HPLC and FTIR method.Materials and MethodsMale albino wistar rats were divided into control, diabetic, diabetic + voglibose, diabetic + glimepiride, diabetic+250, 500, 1000 mg/kg of AEATP, diabetic + glimepiride + voglibose, diabetic + glimepiride+ 250, 500 and 1000 mg/kg AEATP, diabetic + GLP-1 antagonist+250, 500 and 1000 mg/kg AEATP. Plasma glucose, insulin and active GLP-1 levels were measured 15 min after OGTT. Fasting blood glucose, Plasma triglycerides, glycated hemoglobin (HbA1c), Fasting insulin, pancreatic insulin content, ileum and colon GLP-1 content were assessed at 5th week. Association of alpha-glucosidase was also assessed with GLP-1 and insulin.ResultsAEATP significantly attenuated hyperglycemia by increasing insulin level in plasma and pancreas and increased active GLP-1 as well as insulin level in diabetic rats after OGTT. GLP-1 content was significantly increased in ileum and colon by inhibiting alpha-glucosidase. Involvement of GLP-1 in antihyperglycemic effect of AEATP was confirmed by using GLP-1 antagonist. Moreover, AEATP significantly improved dyslipidemia in diabetic rats. HPLC analysis of A. tortilis polysaccharide comprised four specific monosaccharides (Rhamnose, Glucuronic acid, glucose and galactose) and FTIR spectrum shown band at 3430.6 cm-1 (O–H stretching), 2940.3 cm−1 (C–H linkage), 1630.4 cm−1 (carbonyl stretching), 1410 cm−1 (uronic acid) and 1030.5 cm−1 (glycosidic linkage).ConclusionIt can be concluded that antidiabetic effect of AEATP is through the modulation of GLP-1 level in plasma and intestinal tissue via alpha glucosidase inhibition.

Annona cherimola Miller Fruit as a Promising Candidate against Diabetic Complications: An In Vitro Study and Preliminary Clinical Results.

Diabetes is a chronic metabolic disease with a strong social impact worldwide. Under chronic hyperglycemia, protein glycation strongly contributes to diabetes-related complications onset. Anti-glycation agents and inhibitors of α-glucosidase are often therapeutically used to control postprandial glycemia in order to prevent development of long-term diabetic complications. Given drug resistance and adverse effects of conventional antidiabetic therapies, the discovery of new effective and non-toxic naturally occurring compounds is needed to prevent and/or to manage life-threatening diabetic complications. Annona cherimola Miller fruit has been used in Mexican traditional medicine as natural remedy against diabetes. In this work, the in vitro anti-glycation and anti-α-glucosidase roles of Annona cherimola Miller pulp extract (CE) were investigated. Moreover, healthy and diabetic subjects were enrolled in a cross-over design intervention study aimed at investigating the effects of pulp intake on postprandial glycemia. This work shows that CE was able to inhibit albumin glycation in vitro and to inhibit α-glucosidase enzyme. Furthermore, the pulp intake did not contribute to an increase in postprandial glycemia, making it a suitable source of health-promoting phytonutrients and a potential functional food in diabetics and pre-diabetics diet.

A trisaccharide phenylethanoid glycoside from Scrophularia flava Grau with potential anti-type 2 diabetic properties by inhibiting α-glucosidase enzyme and decreasing oxidative stress.

The Scrophularia genus is a rich source of phenylethanoid glycosides, with diverse biological activities including anti-diabetic properties. This study investigated anti-type 2 diabetic potential and active component of Scrophularia flava Grau. A new phenylethanoid glycoside was isolated from aerial parts of the plant and identified as 2-(4-hydroxy-3-methoxyphenyl) ethyl 6-deoxy-3-O-[(2E)-3-(3 hydroxy-4-methoxyphenyl) prop-2-enoyl]-α-rhamnopyranosyl-(1→3)-[α-rhamnopyranosyl-(1→6)]-4-O-[(2E)-3-(4-hydroxy-3-methoxyphenyl) prop-2-enoyl]-β-glucopyranoside. It was named flavaioside. The structure of flavaioside was identified based on 1H NMR, 13C NMR, DEPT-HSQC, COSY, HMBC, NOESY and LC-ESI-MS-MS. Total methanol extract, fractions (A-F) and specific main phenylethanoid glycoside (flavaioside), were assessed for inhibitory effects against the α-glucosidase enzyme (in vitro anti-type 2 diabetic assay). The antioxidant activities of methanol extracts, all fractions and isolated flavaioside were identified based on 2, 2'-diphenyl-1-picrylhydrazyl radical (DPPH) scavenging activity, 2, 2'-azino-bis (3-ethylbenzothiazoline)-6-sulphonic acid radical cation (ABTS+) scavenging activity, phosphomolybdenum method, and metal chelating activity. In comparison to the other fractions, the best antioxidant result was observed in fraction E and its main compound, flavaioside, in DPPH (IC50=4.26, 2.57µg/mL) and ABTS+ (EC50=55.45, 6.34µg/mL) scavenging activities. Flavaioside showed significantly stronger activities than α-tocopherol and ascorbic acid in DPPH and ABTS+ assays. Furthermore, flavaioside showed a potent inhibitory activity on the α-glucosidase enzyme which was comparable with the known anti-type 2 diabetic drug, acarbose (91.85%, and 92.87%, respectively). Fraction E and flavaioside showed α-glucosidase inhibitory activities with IC50 values, 65.05 and 6.50µg/mL. The plant and its isolated flavaioside can possess acceptable anti-type 2 diabetic potential and anti-oxidant activity.

Bioassay-guided isolation and identification of antidiabetic compounds from Garcinia cowa leaf extract

Garcinia cowa Roxb. ex Choisy (Clusiaceae) is a Thai local edible plant, which has been used for the treatment of diabetes. The aim of this study is to discover and identify bioactive compounds related to antidiabetic properties from the leaf extract of G. cowa. α-Glucosidase inhibitory bioassay-guided isolation of the ethyl acetate extract of the leaves of G.cowa resulted in the isolation and identification of 11 compounds. Of these, a decahydro-1H-xanthene derivative, garciniacowone K (1), was identified as a novel compound. Their structures were characterized by spectroscopic data and by comparison of their NMR spectroscopic data with those previously reported. All compounds were evaluated for their α-glucosidase inhibitory and glucose consumption activities. Compound 2 showed the highest efficacy in inhibiting α-glucosidase enzyme and promoting glucose consumption activity by 3T3-L1 cells, with IC50 values of 0.5 μM and 13.1 μM, respectively, without causing toxicity to cells.

Biomass, sinensetin content, and α-glucosidase inhibition activity of orthosiphon aristatus were influenced by fertilization and harvest

Orthosiphon aristatus has been proved as a diabetic remedy due to its anti-hyperglycemic activity. One of its phenolic compounds, sinensetin, has a capability to inhibit α-glucosidase enzyme activity. As cultivation techniques play roles in the medicinal properties of plants, this study was aimed to determine the best fertilization and harvest method to obtain the high yield of dry leaves, sinensetin content and α-glucosidase inhibition activity. The experiment was conducted at Leuwikopo Experimental Farm IPB University, from October 2014 until April 2015 and used a split-split plot design with three replications. The treatments were the technique of organic fertilizer application (whole and split) as the main plot; harvest interval (3, 5 and 7 weeks) as subplot; and cutting height (10, 20 and 30 cm above ground level) as sub-sub plot. The results showed that the whole application of 10 ton ha−1 organic fertilizer produced the higher weight of O. aristatus dry leaves than split application. The crop produced a high weight of dry leaves with the 3- and 5-week harvest interval but produced high sinensetin content with the 7-week harvest interval. O. aristatus harvested by cutting at 30 cm above ground level produced the highest weight of dry leaves, sinensetin content and α-glucosidase activity inhibition.