Alpha-glucosidase Inhibitory Effects Research Articles

Determination of alpha-glucosidase inhibitory effects of anthraquinone aglycons by molecular docking and in vitro studies

Rumex acetosella L. (Polygonaceae) has been commonly used for diabetes in traditional medicine [1]. According to World Health Organization, the global prevalence of diabetes was estimated to be 9% among adults in 2014 [2] and 90% of which was type 2 diabetes [3].

In vitro alpha glucosidase inhibition and free-radical scavenging activity of propolis from Thai stingless bees in mangosteen orchard

The chemical component and biological activity of propolis depend on flora area of bee collection and bee species. In the study, the propolis from three stingless bee species, Lepidotrigona ventralis Smith, Lepidotrigona terminata Smith, and Tetragonula pagdeni Schwarz, was collected in the same region of mangosteen garden from Thailand. Total phenolic content, alpha glucosidase inhibitory effect, and free-radical scavenging activity using FRAP, ABTS, DPPH assays were determined. The most potent activity of propolis extract was investigated for bioactive compounds and their quantity. The ethanol extract of T. pagdeni propolis had the highest total phenolic content 12.83±0.72g of gallic acid equivalents in 100g of the extract, and the strongest alpha glucosidase inhibitory effect with the IC50 of 70.79±6.44μg/ml. The free-radical scavenging activity evaluated by FRAP, ABTS, DPPH assays showed the FRAP value of 279.70±20.55μmol FeSO4 equivalent/g extract and the IC50 of 59.52±10.76 and 122.71±11.76 μg/ml, respectively. Gamma- and alpha-mangostin from T. pagdeni propolis extract were isolated and determined for the biological activity. Gamma-mangostin exhibited the strongest activity for both alpha glucosidase inhibitory effect and free-radical scavenging activity. Using HPLC quantitative analysis method, the content of gamma- and alpha-mangostin in the extract was found to be 0.94±0.01 and 2.77±0.08% (w/w), respectively. These findings suggested that T. pagdeni propolis may be used as a more suitable raw material for nutraceutical and pharmaceutical products and these mangostin derivatives as markers.

New isotonic drinks with antioxidant and biological capacities from berries (maqui, açaí and blackthorn) and lemon juice

The aim of the study was to design new isotonic drinks with lemon juice and berries: maqui [Aristotelia chilensis (Molina) Stuntz], açaí (Euterpe oleracea Mart.) and blackthorn (Prunus spinosa L.), following on from previous research. Quality parameters – including colour (CIELab parameters), minerals, phytochemical identification and quantification by high-performance liquid chromatography with diode array detector, total phenolic content by the Folin–Ciocalteu reagent, the antioxidant capacity (ABTS+, DPPH• and assays) and biological activities (in vitro alpha-glucosidase and lipase inhibitory effects) – were tested in the samples and compared to commercially available isotonic drinks. The new isotonic blends with lemon and anthocyanins-rich berries showed an attractive colour, especially in maqui samples, which is essential for consumer acceptance. Significantly higher antioxidant and biological effects were determined in the new blends, in comparison with the commercial isotonic beverages.

Improved Glycemic Control in Patients with Advanced Type 2 Diabetes Mellitus Taking Urtica dioica Leaf Extract: A Randomized Double-Blind Placebo-Controlled Clinical Trial

Advanced type 2 diabetes mellitus (T2DM) needing insulin therapy is common. Most conventional anti-hyperglycemic drugs have limited efficacies and significant side effects, so that better anti-hyperglycemic agents are needed. Urtica dioica L. (nettle) leaves have insulin secretagogue, PPARgamma agonistic, and alpha-glucosidase inhibitory effects. Moreover, nettle leaves are used in traditional medicine as an anti-hyperglycemic agent to treat diabetes mellitus. Thus, efficacy and safety of nettle in the treatment of patients with advanced type 2 diabetes mellitus needing insulin were studied. In this randomized double-blind placebo-controlled clinical trial, we evaluated the effects of taking nettle leaf extract (one 500 mg capsule every 8 hours for 3 months) combined with the conventional oral anti-hyperglycemic drugs on the blood levels of fasting glucose, postprandial glucose, glycosylated hemoglobin (HbA1c), creatinine and liver enzymes SGOT and SGPT, and systolic and diastolic blood pressures in 46 patients and compared with the placebo group (n = 46). At the endpoint, the extract lowered the blood levels of fasting glucose, 2 hours postprandial glucose, and HbA1c significantly (p < 0.001, p = 0.009, and p = 0.006, respectively) without any significant effects on the other parameters (p > 0.05) compared with placebo. Nettle may safely improve glycemic control in type 2 diabetic patients needing insulin therapy.

Inhibition of Alpha-Glucosidase by Acacia nilotica Prevents Hyperglycemia along with Improvement of Diabetic Complications via Aldose Reductase Inhibition

Postprandial hyperglycemia is a prominent and early defect in diabetes and regulating blood glucose elevation may attenuate progression towards diabetes associated secondary complications. Here we investigated the alphaglucosidase inhibitory potential of the ethanolic extract of the stem bark of Acacia nilotica (EEAN). The EEAN showed a remarkable alpha-glucosidase inhibitory effect with IC50 value around 8 μg/ml. Kinetic studies revealed that the extract inhibited alpha-glucosidase in competitive manner and caused conformational changes in secondary structure of the enzyme protein. In vivo analysis showed that EEAN significantly suppresses the sucrose-induced postprandial glucose elevation in normal rats and exerts antihyperglycemic effect in streptozotocin (STZ)-induced diabetic rats in a dose-dependent fashion. Further, treatment of diabetic animals after 10 week of STZ-treatment with EEAN (250 mg/ kg) for 21 days, significantly reduced the elevated levels of blood glucose, %HbA1C, urea, uric acid and creatinine, and significantly increased the depressed plasma insulin level. The EEAN also showed inhibitory potential on aldose reductase activity with an IC50 of 7.5 μg/ml. The results suggest that EEAN possess antihyperglycemic activity through inhibition of alpha-glucosidase along with antidiabetogenic effect on polyol pathway through aldose reductase inhibition.

Alpha glucosidase inhibitory effect and enzyme kinetics of coastal medicinal plants

Numerous metabolic disorders and diseases associated with the glucosidase enzyme activity. Therefore, in the present study we evaluated alpha glucosidase inhibitory effect of coastal medicinal plants on Saccharomyces cerevisiae alpha-glucosidase to control postprandial hyperglycemia. The n-hexane extracts of study plants screened for alpha-glucosidase inhibitory activity using yeast glucosidase. The enzyme kinetics studied Line weaver burk plot method. Among the ten plants Citrullus colocynthis, Aegle marmelos and Ipomoea pescaprae exhibited potent alpha-glucosidase inhibitory activity, 85.9 ±0.10, 72.23 ± 0.30 and 67.9 ± 0.11 respectively. From the enzyme kinetics assay potent plants contain uncompetitive inhibitors of alpha glucosidase. C. colocynthis, A. marmelos and Ipomoea pescaprae have potential alpha-glucosidase inhibitors that can exploited for its used to treat diabetes.

Fermentation process enhanced production and bioactivities of oolong tea polysaccharides

Oolong tea (OT) is unique for its flavor and healthy effects. We have reported that the polypheonols of OT possessed antioxidant anticancer, and hypolipidemic effects. In addition, tea polysaccharides (TPS) have long been recognized to have antioxidant, immunomodulatory and antidiabetic properties. Since there are three typical kinds of OTs, e.g. Tieguanyin, Fenghuangdancong and Dahongpao with the lightest, intermediate and the highest degree of fermentation respectively, it is important for us to know whether fermentation degree affected the production and their bioactivities of tea polysaccharide. In the present study, three polysaccharides named TTPS, FTPS and DTPS were isolated from these three typical kinds of oolong teas in the above order respectively. Physicochemical characteristics, in vitro antioxidant activity and alpha-glucosidase inhibitory effect of TTPS, FTPS and DTPS were studied. Analysis of the chemical compositions (protein, rot neutral sugars and uronic acid) revealed that they all belonged to acid heteropolysaccharides bound with protein. The contents of protein and uronic acid but rot neutral sugars proportionally increased with degree of fermentation, highest in DTPS, which significantly correlated with their potencies in antioxidant and alpha-glucosidase inhibitory activities. Analysis of neutral sugar compositions showed that they all contained seven monosaccharides with different molar ratio. Measurements of their molecular weight by high performance gel permeation chromatography indicated that 92.9% of TTPS and 94.4% of DTPS had a peak of molecular weight of 0.82×106 and 2.64×106 respectively, but that of FTPS had 34.2% with 0.93×106 and 68.8% with 0.01×106 respectively. Fourier Transform IR spectra exhibited that they all had similar characteristic absorption bands of uronic acid, protein, polysaccharide and pyran-glycosides respectively. Furthermore, measurements of antioxidant activities by assays of DPPH, ABTS and ferric-reducing antioxidant power (FRAP) showed that DTPS was the most potent, FTPS the next and TTPS the least respectively. Similarly, DTPS possessed the strongest inhibitory potential against alpha-glucosidase activity, followed by FTPS and then TTPS. The potencies of the bioactivities of these three OTPS were apparently proportional to their contents of protein and uronic acid, suggesting that the higher degree of fermentation of oolong teas produced higher contents of protein-bound acid heteropolysaccharides accompanied with higher antioxidant and alpha-glucosidase inhibitory activities. Perhaps, DTPS had a potential to play a role in prevention of type 2 diabetes mellitus. Further studies to confirm this contention is in progression.

Comparison of biological activities of Ribes fasciculatum according to regional differences

Ribes fasciculatum has been traditionally used as febrifuge, diuretic and antidote against urushiol in Korea, although its biological functions have not been well studied. In this study, we determined the anti-oxidant activities, anti-microbial activities and α-glucosidase inhibitory effects of methanol extract and the fractions of R. fasciculatum stem from Chuncheon and Jeju in South Korea. The highest anti-oxidant activity obtained by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging assay and reducing power assay was found in the EtOAc fraction from Jeju-MeOH extract, which contained the highest level of total phenolic compounds compared to the other fractions. In addition, EtOAc fraction from Chuncheon-MeOH extract exhibited higher inhibitory activities against α-glucosidase (IC50 = 4.38 ug/ml) compared to the IC50 of the EtOAc fraction from Jeju-MeOH extract. Chuncheon-MeOH extract showed antimicrobial activities against Staphylococus aureus,Escherichia coli and Pichia jadinii. Although, extracts obtained from two regions contained different biological activities, these in vitro studies indicate that this plant can likely be a potential medicinal plant resource for developing effective dietary health supplements. Key words: Anti-oxidant activity, anti-microbial activity, alpha glucosidase inhibitory effect,Ribes fasciculatum.

Azadirachtolide: An anti-diabetic and hypolipidemic effects from Azadirachta indica leaves

Introduction: Azadirachta indica (Meliaceae) leaves are used traditionally in the Indian Ayurvedic medicinal system to treat diabetes. The aim of the present study is to investigate the effect of azadirachtolide (tetranortriterpenoid from Azadirachta indica leaves) on blood glucose and serum lipid profiles on streptozotocin-induced diabetic rats. Methods: Streptozotocin-induced diabetic rats were used for the study. Azadirachtolide (at a dose 50 and 100 mg/kg) was administrated intra-peritoneally in diabetic rats once a week for 30 days. Biochemical parameters notably fasting blood sugar, total cholesterol, triglycerides, low-density lipoprotein, very low-density lipoprotein and high-density lipoprotein were determined. The in vitro alpha amylase and alpha glucosidase inhibitory effects of azadirachtolide were measured and IC 50 values were determined. Results: Azadirachtolide exhibited significant (P < 0.05) anti-diabetic as well as hypolipidemic effects by lowering FBS, TC, TG, LDL, and VLDL levels; but also with elevation of HDL level in diabetic rats. Azadirachtolide showed appreciable alpha amylase (IC 50 value of 55.80 ± 1.7 µg/ml) and alpha glucosidase inhibitory effects (IC 50 value of 47.85 ± 1.4 µg/ ml) compared with acarbose (IC 50 value of 83.33 ± 1.8 µg/ml). Conclusion: The present study indicated that azadirachtolide possesses anti-hyperglycemic and anti-lipidemic effects. Thus, results suggested azadirachtolide has a beneficial effect in the management of diabetes associated with abnormal lipid profile and related cardiovascular complications.

Alpha glucosidase inhibitory effect, anti-microbial activity and UPLC analysis of Rhus verniciflua under various extract conditions

In the present study, crude extract of Rhus verniciflua stem was screened for its α-glucosidase inhibitory effects and anti-microbial activity using different extraction ratios of water to alcohol. Ultra performance liquid chromatography (UPLC) was used to quantify compounds (fustin, gallic acid, 3', 4', 7-trihydroxyflavone, and fisetin). Ethanolic extract showed higher α-glucosidase inhibitory effect than methanolic extract, whereas distilled water extract did not inhibit α-glucosidase at all. Especially, neat alcoholic (methanolic or ethanolic) extracts exhibited stronger inhibitory activities compared to their corresponding aqueous mixtures. Analysis of the UPLC chromatogram showed that fustin (from 28.5 to 151.7 mg/g extract) was the major compound of R. verniciflua stem. One-hundred percent ethanolic extracts produced inhibition zones against Staphylococcus aureus with the largest diameters (15 mm). The result from this study provides suitable support for the use of R. verniciflua in the treatment of diabetes and for the control of infectious disease caused by S. aureus. Key words: Rhus verniciflua, anti-microbial activity, α-glucosidase inhibitory effect.

Studies on the anti-diabetic and hypolipidemic potentials of mangiferin (Xanthone Glucoside) in streptozotocin-induced Type 1 and Type 2 diabetic model rats.

Context: Mangifera indica (Anacardiaceae) stem bark contains a rich content of mangiferin and is used traditionally in Indian Ayurvedic system to treat diabetes. Purpose of the study: To investigate anti-diabetic and hypolipidemic effects of mangiferin in type 1 and type 2 diabetic rats models. Streptozotocin was used to induce type 1 and type 2 diabetic rats. Mangiferin (at a dose 10 and 20mg/kg) was administrated intra-peritoneally in type 1 and type 2 diabetic rats daily up to 30 days. Biochemical parameters notably fasting blood sugar, total cholesterol, triglycerides, low-density lipoprotein, very low-density lipoprotein and high-density lipoprotein were estimated. In addition, in vitro alpha amylase and alpha glucosidase inhibitory effects of mangiferin were performed and IC50 values were determined. Results: Mangiferin exhibited significant (P<0.05) anti-diabetic as well as hypolipidemic effects by lowering FBS, TC, TG, LDL, and VLDL levels; but also with elevation of HDL level in type 2 diabetic model rats. In addition, mangiferin showed appreciable alpha amylase inhibitory effect (IC50 value 74.35±1.9µg/ml) and alpha glucosidase inhibitory effect (IC50 41.88±3.9µg/ml) when compared with standard drug acarbose (IC50 83.33±1.2µg/ml). Conclusions: Mangiferin showed anti-diabetic as well as hypolipidemic potentials in type 2 diabetic model rats. Therefore, mangiferin possess beneficial effects in the management of type 2 diabetes with hyperlipidemia.

Insulin releasing and alpha-glucosidase inhibitory activity of ethyl acetate fraction of Acorus calamus in vitro and in vivo

Ethnopharmacological relevance The radix of Acorus calamus L. (AC) is widely used in the therapy of diabetes in traditional folk medicine of America and Indonesia, and we previously reported the insulin sensitizing activity of the ethyl acetate fraction of AC (ACE). Aim of the study To investigate the insulin releasing and alpha-glucosidase inhibitory activity of ACE in vitro and in vivo. Materials and methods Insulin releasing and alpha-glucosidase inhibitory effects of different fractions from AC were detected in vitro using HIT-T15 cell line and alpha-glucosidase enzyme. Furthermore, effects of ACE orally on serum glucose were detected in fasted and glucose/amylum challenged normal mice. Results AC and ACE increased insulin secretion in HIT-T15 cells as gliclazide did. As in vivo results, ACE (400 and 800 mg/kg) significantly decreased fasting serum glucose, and suppressed the increase of blood glucose levels after 2 g/kg glucose loading in normal mice. In addition, ACE as a mixed-type inhibitor inhibited alpha-glucosidase activity in vitro with an IC 50 of 0.41 μg/ml, and 100 mg/kg of it clearly reduced the increase of blood glucose levels after 5 g/kg amylum loading in normal mice. Conclusions Apart from its insulin sensitizing effect, ACE may have hypoglycemic effects via mechanisms of insulin releasing and alpha-glucosidase inhibition, and thus improves postprandial hyperglycemia and cardiovascular complications.

&amp;alpha;-Glucosidase Inhibition Properties of Cucurbitane-Type Triterpene Glycosides from the Fruits of &lt;i&gt;Momordica charantia&lt;/i&gt;

Fourteen cucurbitane-type triterpene glycosides (1-14) were isolated from a methanol extract of Momordica charantia fruits, including three new compounds, charantosides A-C (1, 5, 6). Their structures were elucidated by chemical and spectroscopic methods. All isolated compounds were evaluated for alpha-glucosidase inhibitory effect. Of which, 12 and 13 showed moderate inhibitory activity against alpha-glucosidase. Whereas, 2, 3, 6-11, and 14 showed weak inhibitory activity, and 1, 4, and 5 were inactive.

Alpha-glucosidase inhibitory effect of anti-diabetic metal ions and their complexes

We found alpha-glucosidase inhibitory (α-GI) effect of metal ions and their complexes which showed the high blood glucose lowering effect in diabetic model animals. The Cu(II) ion and its complexes showed strong α-GI activity greater than clinically used acarbose in in vitro studies. Furthermore, in in vivo experiments, α-GI action was newly discovered in normal ddy mice. These results suggested that one of action mechanisms of the anti-diabetic metal ions and complexes is related to the α-GI effects.

In vitro alpha-glucosidase and alpha-amylase enzyme inhibitory effects of Andrographis paniculata extract and andrographolide.

There has been an enormous interest in the development of alternative medicines for type 2 diabetes, specifically screening for phytochemicals with the ability to delay or prevent glucose absorption. The goal of the present study was to provide in vitro evidence for potential inhibition of alpha-glucosidase and alpha-amylase enzymes, followed by a confirmatory in vivo study on rats to generate a stronger biochemical rationale for further studies on the ethanolic extract of Andrographis paniculata and andrographolide. The extract showed appreciable alpha-glucosidase inhibitory effect in a concentration-dependent manner (IC(50)=17.2+/-0.15 mg/ml) and a weak alpha-amylase inhibitory activity (IC(50)=50.9+/-0.17 mg/ml). Andrographolide demonstrated a similar (IC(50)=11.0+/-0.28 mg/ml) alpha-glucosidase and alpha-amylase inhibitory activity (IC(50)=11.3+/-0.29 mg/ml). The positive in vitro enzyme inhibition tests paved way for confirmatory in vivo studies. The in vivo studies demonstrated that A. paniculata extract significantly (P<0.05) reduced peak blood glucose and area under curve in diabetic rats when challenged with oral administration of starch and sucrose. Further, andrographolide also caused a significant (P<0.05) reduction in peak blood glucose and area under the curve in diabetic rats. Hence alpha-glucosidase inhibition may possibly be one of the mechanisms for the A. paniculata extract to exert antidiabetic activity and indicates that AP extract can be considered as a potential candidate for the management of type 2 diabetes mellitus.

Antidiabetic properties of polysaccharide- and polyphenolic-enriched fractions from the brown seaweed Ascophyllum nodosum.

We screened seaweed species from Atlantic Canada for antidiabetic activity by testing extracts for alpha-glucosidase inhibitory effect and glucose uptake stimulatory activity. An aqueous ethanolic extract of Ascophyllum nodosum was found to be active in both assays, inhibiting rat intestinal alpha-glucosidase (IC50 = 77 microg/mL) and stimulating basal glucose uptake into 3T3-L1 adipocytes during a 20-minute incubation by about 3-fold (at 400 microg/mL extract). Bioassay-guided fractionation of the A. nodosum extract showed that alpha-glucosidase inhibition was associated with polyphenolic components in the extract. These polyphenolics, along with other constituents appeared to be responsible for the stimulatory activity on glucose uptake. However, attempts to further concentrate this activity through fractionation techniques were unsuccessful. A crude polyphenol extract (PPE), an enriched polyphenolic fraction (PPE-F1) and a polysaccharide extract (PSE) were prepared from commercial A. nodosum powder and administered to streptozotocin-diabetic mice for up to 4-weeks by daily gavage at 200 mg/kg body mass. PPE and PPE-F1 improved fasting serum glucose level in diabetic mice; however, the effect was only statistically significant at day 14. In addition, PPE-F1 was shown to blunt the rise in blood glucose after an oral sucrose tolerance test in diabetic mice. Mice treated with PPE and PPE-F1 had decreased blood total cholesterol and glycated serum protein levels compared with untreated diabetic mice, whereas PPE also normalized the reduction in liver glycogen level that occurred in diabetic animals. All 3 A. nodosum preparations improved blood antioxidant capacity.

In Vitro Alpha-glucosidase Inhibitory Effect of Zn(II) Complex with 6-Methyl-2-picolinmethylamide

We found alpha-glucosidase inhibitory effect of Zn(II) complex with 6-methyl-2-picolinmethylamide (6mpa-ma) which showed the highest blood glucose lowering effect in Zn(II) complexes with picolinamide derivatives in KK-A(y) mice. The Zn(II) complex showed strong alpha-glucosidase inhibitory activity greater by about eighty times (substrate: maltose) and forty times (substrate: sucrose) compared with acarbose.

Inhibitory effects of hyssop (Hyssopus officinalis) extracts on intestinal alpha-glucosidase activity and postprandial hyperglycemia.

It has been known that Hyssopus officinalis (hyssop) is a herb that grows in the wild and is a source of natural antioxidants. We previously reported that a-glucosidase inhibitors, (2S, 3S)1-O-beta-D-6'-O-cinnamoylglucopyranosyl-3-(3", 5"-dimethoxy-4"-hydroxyphenyl)-1,2,3-propanetriol and (2S, 3S)1-O-beta-D-glucopranosyl-3-(3", 5"-dimethoxy-4"-hydroxyphenyl)-1,2,3-propanetriol, from the dry leaves of hyssop, were isolated. This study examined the alpha-glucosidase inhibitory effects of hyssop extracts on intestinal carbohydrate absorption in rat everted gut sac and carbohydrate-loaded hyperglycemia in mice. In the everted gut sac experiment, 10 mM sucrose- and 5 mM maltose-treated increases in glucose concentration in the serosal compartment were inhibited in the presence of 0.5 and 1.0 mg/ mL hyssop extracts, although a 10 mM glucose-induced increase in serosal glucose was not inhibited by the extracts. Additionally, hyperglycemia in sucrose- and maltose-loaded mice was significantly suppressed at an early stage, within 30 to 60 min by oral pre-administration of 300 and 100 mg/kg hyssop extracts, respectively. These findings suggest that hyssop extracts inhibited the digestion of complex carbohydrates, but not that of absorbable monosaccharide, and might be a useful supplemental food for hyperglycemia.

Alpha-glucosidase inhibition from a Chinese medical herb (Ramulus mori) in normal and diabetic rats and mice.

Alpha-glucosidase inhibitors are oral antidiabetic drugs. A traditional Chinese medical herb, Sangzhi (Ramulus mori), appears to have properties similar to those of alpha-glucosidase inhibitors. The effects of an aqueous extract of Shangzhi (SZ) were studied in normal and alloxan diabetic rats and mice, and these results compared with those for acarbose, an alpha-glucosidase inhibitor. In our grade-dose studies, SZ was found to lower and prolong the zenith of blood glucose concentration (ZBG) after sucrose or starch loading and stabilize blood glucose levels in fasting normal and alloxan diabetic mice. After 2 weeks of SZ administration with high-calorie chow or a normal diet, the fasting and non-fasting blood glucose concentrations in alloxan diabetic mice and rats were decreased. In alloxan rats, the blood fructosamine concentration was lowered. Results for acarbose and SZ were similar. These indicate that SZ has alpha-glucosidase inhibitory effects.