Background: One of the therapeutic strategies for type 2 diabetes mellitus involves suppressing postprandial hyperglycemia by inhibiting key enzymes in carbohydrate digestion, α-glucosidase and α-amylase. While such inhibitors are commercially available, some researchers have turned to plants for potentially cheaper and safer alternatives. Objectives: The study aimed to investigate the in vitro α-glucosidase and α-amylase inhibitory activities of the leaf methanolic extracts of two native Philippine plants Ficus nota Blanco Merr. and Ficus septica Burm F, as well as their effects on postprandial blood glucose levels in a mouse model. Methodology: The in vitro activities of the leaf methanolic extracts were evaluated against porcine pancreatic α-amylase and yeast αglucosidase. The most active extract was partially purified into fractions by sequential solvent partitioning and subjected to in vitro testing. Postprandial antihyperglycemic activity was then assessed in normoglycemic ICR mice. Phytochemical analysis was also performed Results: The most active extract and fraction in vitro were FS-crude and FS-HexF, respectively, having significantly more potent αglucosidase inhibitory activity than the commercial drug acarbose. FS-crude and FS-HexF exhibited strong inhibition of αglucosidase and weak inhibition of α-amylase, which is considered favorable for novel inhibitors as it is hypothesized to reduce gastrointestinal adverse effects. However, FS-crude and FS-HexF did not significantly attenuate postprandial blood glucose levels in the oral starch tolerance test. Phytochemical analysis of FS-HexF putatively identified 6-gingerol as one of the possible bioactive components. Conclusion F. septica could be a potential source of glycoside inhibitors as it showed promising in vitro inhibition of α-amylase and α-glucosidase. While it did not exhibit significant postprandial antihyperglycemic activity in this study, more robust testing is recommended to make a definitive conclusion.
Amylases ; Glucosidases ; Hypoglycemic Agents

BACKGROUND: Voglibose is an alpha-glucosidase inhibitor. The purpose of this study was to evaluate the pharmacodynamic characteristics of voglibose for determining the appropriate study design and parameters for a pharmacodynamic equivalence study of voglibose. METHODS: This study consisted of two studies. The single dose study had an open and single sequence design. Nineteen subjects received placebo and then one tablet of voglibose on two consecutive days with sucrose. The multiple dose study was performed with the similar design, except that it was a multiple dose of the single dose study. Nine subjects who showed an effective response in the single dose study received placebo three times and then voglibose 4 times on two consecutive days. Serial blood samples for pharmacodynamic parameters were taken until 180 mins after each administration. The baseline adjusted maximum serum glucose level (G(max)) and area under the serum glucose level-time profiles were determined and compared. RESULTS: In the single dose study, the difference in G(max) was -10.6 +/- 28.7 mg/dL. The area under the serum glucose concentration-time curve (AUGC(0-1h)) of placebo and voglibose were 7825.0 +/- 1145.3 mg.min/dL, 7907.5 +/- 917.2 mg.min/dL, respectively. In the multiple dose study, the difference in G(max) was 46.6 +/- 16.1 mg/dL. The AUGC(0-1h) of placebo and voglibose were 8138.6 +/- 721.9 mg.min/dL and 6499.7 +/- 447.2 mg.min/dL, respectively. The G(max) and AUGC(0-1h) of the multiple dose study was significantly different between placebo and voglibose in paired t-test. CONCLUSION: The differences in G(max) and AUGC(0-1h) are suitable for pharmacodynamic parameters to evaluate bioequivalence of voglibose.
alpha-Glucosidases ; Glucose ; Inositol ; Sucrose ; Therapeutic Equivalency

Aims: The study aimed to investigate the effect of glucose on alpha-amylase and glucoamylase production in some Indonesian indigenous fungi. Methodology and results: Fungi were screened for their ability to produce alpha-amylase and glucoamylase in the presence of glucose. The strains were grown in a medium containing starch and glucose as carbon sources with glucose concentrations varying from 0 to 5% for four days, and the alpha-amylase and glucoamylase were analyzed at the end of the growth period. Most strains showed repression on the amylases production when glucose was added to the medium. However, some strains showed no repression on amylases production when glucose was supplemented to the medium. The addition of glucose repressed glucoamylase production, but no repression on alpha-amylase was noted for strain KKB4, vice versa, there was repression on alpha-amylase production but no repression on glucoamylase production for strain FIG1. Strains FNCC 6151 and MLT1J1 showed no repression on both alpha-amylase and glucoamylase production when glucose was added to the medium up to 5%. The occurrence of repression in the production of alpha-amylase and glucoamylase was strain-specific. Conclusion, significance and impact of study Out of the nine indigenous fungi strains examined, strains FNCC 6151 and MLT1J1 showed no repression on both alpha-amylase and glucoamylase production when glucose was added to the medium up to 5%. Those two strains have the potential to be improved further to produce both alpha-amylase and glucoamylase.
Glucosidases ; alpha-Amylases ; Glucan 1,4-alpha-Glucosidase

This study investigated the antioxidant activity of methanol (MeOH) and water extracts from roots of Cirsium japonicum in vitro. MeOH extract showed a stronger free radical scavenging activity than water extract. However, both of extracts showed a concentration dependent hydroxyl radical scavenging activity, reducing power and metal chelating ability. MeOH extract had greater phenolic and flavonoid contents than water extract. The antidiabetic activity of these two extracts was evaluated by the alpha-glucosidase inhibition assay. The water extract showed a considerable alpha-glucosidase inhibitory activity. To our knowledge, this may be the first time to report the antioxidant and antidiabetic activities in Cirsium japonicum roots.
alpha-Glucosidases ; Cirsium ; Hydroxyl Radical ; Methanol ; Phenol ; Water

The chemical constituents of the seeds of Moringa oleifera were isolated and purified by using Sephadex LH-20, Toyo-pearl HW-40F, silica gel, ODS, and MCI column chromatography. The structures of compounds were identified by high-resolution mass spectrometry, ~1H-NMR, ~(13)C-NMR, HMQC, HMBC, and ~1H-~1H COSY, as well as physicochemical properties of compounds and literature data. Twelve compounds were isolated from 30% ethanol fraction of the seeds of M. oleifera and identified as ethyl-4-O-α-L-rhamnosyl-α-L-rhamnoside(1), ethyl-3-O-α-L-rhamnosyl-α-L-rhamnoside(2),(4-hydroxybenzyl)ethyl carbamate(3),(4-aminophenyl)acetic acid(4), ethyl-α-L-rhamnoside(5), methyl-α-L-rhamnoside(6), moringapyranosyl(7), 2-[4-(α-L-rhamnosyl)phenyl]methyl acetate(8), niaziridin(9), 5-hydroxymethyl furfural(10), 4-hydroxybenzeneacetamide(11), and 4-hydroxybenzoic acid(12). Among them, compounds 1 and 2 are two new compounds, compound 3 is a new natural product, and compounds 4-5 were yielded from Moringa plant for the first time. All compounds were evaluated for α-glucosidase inhibitory activity in vitro. Compound 10 showed excellent inhibitory activity with IC_(50) of 210 μg·mL~(-1).
Moringa oleifera/chemistry* ; alpha-Glucosidases ; Moringa ; Seeds ; Plant Extracts/pharmacology*

Aims: This study aimed to evaluate antidiabetic potential of indigenous Lactobacillus isolates by measuring the ability of α-glucosidase inhibitory (AGI) and antioxidant activity. The mechanism of probiotics as antidiabetic can occur through the AGI and antioxidant activity of LAB, which is able to suppress oxidative stress that causes chronic inflammation and pancreatic β cell apoptosis, and then through the ability to produce exopolysaccharide (EPS) and short chain fatty acids (SCFA). Methodology and results: MRS broth enriched with 10% glucose was selected as the growth medium for Lactobacillus. The growth medium was then centrifuged to obtain CFS and CFE was produced by extracting the medium with 96% ethanol as a solvent. The results showed that Lactobacillus pentosus MK42 had the highest AGI activity of 80.32 ± 2.20%. Antioxidant activity was not significantly different (P>0.05) among the tested Lactobacillus isolates. Lactobacillus paracasei RK41 produced the highest EPS (360.13 ± 50.01 mg/L), which was not significantly different (P>0.05) from Lactobacillus plantarum1 RB210. All Lactobacillus isolates were able to produce acetic acid, but not all were able to produce propionic and butyric acid. The highest propionic acid was produced by L. plantarum1 RB210 at 0.40 ± 0.31 mmol/L and the highest butyric acid was produced by L. plantarum1 MK2 at 0.22 ± 0.08 mmol/L. Conclusion, significance and impact of study The results show definitively that indigenous Lactobacillus isolates have considerable α-glucosidase inhibitor, antioxidant activity and the ability to produce of EPS and SCFA. This preliminary study suggests the use of indigenous Lactobacillus isolates which have the potential as antidiabetic agent, although the responsible compounds are unknown.
alpha-Glucosidases ; Antioxidants ; Lactobacillus--isolation & ; purification ; Hypoglycemic Agents

This study was conducted in order to compare the biological activities of leaf and root water extracts of Smilax china L. (SC) by measuring the total polyphenol and flavonoid contents, anti-oxidant activity, inhibitory effect on alpha-glucosidase, and anti-inflammatory gene expression. The total polyphenol and flavonoid contents of SC leaf (SCLE) and root (SCRE) water extracts were 127.93 mg GAE/g and 39.50 mg GAE/g and 41.99 mg QE/g and 1.25 mg QE/g, respectively. The anti-oxidative activities of SCLE and SCRE were measured using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical scavenging activity assay and reducing power assay. Both SCLE and SCRE scavenged radicals in a concentration-dependent manner, and SCLE showed stronger radical scavenging activity and reducing power than SCRE; however, both SCLE and SCRE exhibited lower activities than ascorbic acid. Compared to the anti-diabetic drug acarbose, which was used as a positive control, SCLE and SCRE exhibited low alpha-glucosidase inhibition activities; nevertheless, the activity of SCLE was 3.7 fold higher than that of SCRE. Finally, SCLE caused significantly decreased expression of the LPS-induced cytokines, iNOS, and COX-2 mRNA in RAW264.7 cells, indicating anti-inflammatory activity. These results indicate that SCLE might be a potential candidate as an anti-oxidant, anti-diabetic, and anti-inflammatory agent.
Acarbose ; alpha-Glucosidases ; Ascorbic Acid ; Biphenyl Compounds ; China ; Cytokines ; Gene Expression ; Picrates ; RNA, Messenger ; Smilax ; Water

BACKGROUND/OBJECTIVES: In Asia, various medicinal plants have been used as the primary sources in the health care regimen for thousands of years. In recent decades, various studies have investigated the biological activity and potential medicinal value of the medicinal plants. In this study, 100 methanol extracts from 98 plant species were evaluated for their biological activities. MATERIALS/METHODS: The research properties, including 1,1-diphenyl-2-pic-rylhydrazyl (DPPH) radical scavenging activity, alpha-glucosidase and alpha-tyrosinase inhibitory effects, anti-inflammatory activity, and anticancer activity were evaluated for the selected extracts. RESULTS: Fifteen of the extracts scavenged more than 90% of the DPPH radical. Among the extracts, approximately 20 extracts showed a strong inhibitory effect on alpha-glucosidase, while most had no effect on alpha-tyrosinase. In addition, 52% of the extracts showed low toxicity to normal cells, and parts of the extracts exhibited high anti-inflammatory and anticancer activities on the murine macrophage cell (RAW 264.7) and human colon cancer cell (HT-29) lines, respectively. CONCLUSIONS: Our findings may contribute to further nutrition and pharmacological studies. Detailed investigations of the outstanding samples are currently underway.
alpha-Glucosidases ; Asia* ; Colonic Neoplasms ; Delivery of Health Care ; Humans ; Macrophages ; Methanol* ; Plants ; Plants, Medicinal*

BACKGROUND: To evaluate the clinical efficacy of sitagliptin for reducing plasma glucose levels in Korean subjects with type 2 diabetes mellitus during a 14-week treatment period. METHODS: Our study design involved the addition of 100 mg sitagliptin once-daily to three ongoing combination therapy regimens and changing from glimepiride and metformin to sitagliptin and metformin. RESULTS: The addition of sitagliptin 100 mg/day produced a statistically significant reduction in mean HbA1c level (mean HbA1c reduction of 0.99+/-0.85%, P<0.01). In the group taking a combination of sitagliptin and metformin (n=143, initial mean HbA1c level=7.48%), the reductions in HbA1c, 2-hour postprandial glucose, and fasting glucose levels were 0.72+/-0.76% (P<0.01), 47+/-65 mg/dL (P<0.01), and 15+/-44 mg/dL (P<0.01), respectively. In the group taking a combination of sitagliptin, glimepiride, and metformin (n=125, initial mean HbA1c level=8.42%), the reductions in HbA1c, 2-hour postprandial glucose, and fasting glucose levels were 1.09+/-0.86% (P<0.01), 62+/-64 mg/dL (P<0.01), and 31+/-45 mg/dL (P<0.01), respectively. In the group taking a combination of sitagliptin, glimepiride, metformin, and alpha-glucosidase inhibitor (n=63, initial mean HbA1c level=9.19%), the reductions in HbA1c, 2-hour postprandial glucose, and fasting glucose levels were 1.27+/-0.70% (P<0.01), 72+/-65 mg/dL (P<0.01), and 35+/-51 mg/dL (P<0.01), respectively. In the group that had previous hypoglycemic events and that changed from glimepiride to sitagliptin, HbA1c level did not change but fasting glucose increased significantly (14+/-29 mg/dL, P<0.01). CONCLUSION: Sitagliptin combination therapy for 14 weeks significantly improved glycemic control and was well-tolerated in Korean subjects with type 2 diabetes mellitus.
alpha-Glucosidases ; Diabetes Mellitus, Type 2 ; Fasting ; Glucose ; Metformin ; Plasma ; Pyrazines ; Sulfonylurea Compounds ; Triazoles ; Sitagliptin Phosphate

A high activity isoflavone-glucosidase, which hydrolysis glycosides, was obtainde using liquid fermentation from Absidia sp. R strain. The isoflavone-glucosidase was purified 11 folds with yielding rate of 10.9% after ammonium sulfate precipitation and DEAE-Cellocuse (DE-52) ion exchange chromatography. SDS-PAGE results showed that the molecular weight is 53kD. And the optimum temperature, the optimum pH, Km and pI of the enzyme are 50 deegrees C, 5.0, 1.3 x 10(-2) mol/L and 3.2, respectively. The isoflavone-glucosidase is also rather stable under 60 degrees C and in pH range from 5.0 to 7.0. The enzyme can be activated by Co2+ and Ca2+, and be inhibited by Ag+ and Cu2+.
Absidia ; enzymology ; Glucosidases ; isolation & purification ; metabolism ; Hydrogen-Ion Concentration ; Isoflavones ; metabolism ; Temperature