The present study was conducted to develop new inhibitors of pancreatic lipase and alpha-glucosidase from Chinese dietary herbs. Sixty-three dietary herbs from 39 taxonomic families were selected and extracted with aqueous ethanol or water. The extracts were then tested with in vitro enzyme assays for their ability to inhibit pancreatic lipase and alpha-glucosidase activities. Orlistat and acarbose were used as two positive controls. The extracts of Nelumbo nucifera, Curcuma longa, Piper longum and Morus alba showed strong pancreatic lipase inhibitory effects with IC50 at (28.00 +/- 5.51), (5.24 +/- 0.51), (14.76 +/- 2.58), (4.78 +/- 0.58), (3.41 +/- 0.67) mg x L(-1), respectively. These extracts also showed potent alpha-glucosidase inhibitory activities with IC50 at (1.98 +/- 0.13), (0. 18 + 0.007), (0.71 +/- 0.08), (0.077 +/- 0.005), (0.089 +/- 0.006) g x L(-1), respectively. The results provide useful information for developing new drugs or natural health products for hyperlipidemia and hypoglycemia from Chinese dietary herbs.
Curcuma ; chemistry ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Enzyme Inhibitors ; chemistry ; pharmacology ; Lipase ; antagonists & inhibitors ; Morus ; chemistry ; Nelumbo ; chemistry ; Pancreas ; enzymology ; Piper ; chemistry ; Plant Extracts ; chemistry ; pharmacology ; alpha-Glucosidases ; metabolism

OBJECTIVETo study the active compounds from the rhizomes of Musa basjoo.

METHODAntioxidant and alpha-glucosidase inhibitory activity of different extracts were tested. Using bioassay-guided fractionation, the chemical constituents in EtOAC extracts were isolated by column chromatography and identified by MS and NMR spectroscopy.

RESULTFive compounds were isolated and identified as 2',3, 4'-trihydroxyflavone (1), 3,3'-bis-hydroxyanigorufone (2), irenolone (3), 4-dihydroxy-9-(4'-hydroxyphenyl)-phenalenone (4) and 3,4-dihydroxybenzaldehyde (5). Compound 1(IC50 8.61 mg x L(-1)), 3 (IC50 19.55 mg x L(-1)) and 5 (IC50 1.1 mg x L(-1)) had antioxidant activity. Compound 2 (IC50 24.15 mg x L(-1)) and 4(IC50 2.81 mg x L(-1)) had alpha-glucosidase inhibitory activity. Compound 5 showed MIC of 0.078, 0.313, 0.039 microg/disc against SA, MRSA and ESBLs, respectively.

CONCLUSIONCompound 1-5 were isolated from this plant for the first time. Compound 5 was isolated from the genus Musa for the first time. All compound except 5 were first reported about activity.

Bacterial Proteins ; analysis ; antagonists & inhibitors ; Enzyme Inhibitors ; analysis ; isolation & purification ; pharmacology ; Glycoside Hydrolase Inhibitors ; Musa ; chemistry ; Plant Extracts ; analysis ; isolation & purification ; pharmacology ; Rhizome ; chemistry ; Staphylococcus aureus ; drug effects ; enzymology ; alpha-Glucosidases ; analysis

OBJECTIVETo investigate and compare the inhibitory properties of free and bound phenolic extracts of clove bud against carbohydrate hydrolyzing enzymes (alpha-amylase & alpha-glucosidase) and Fe(2+)-induced lipid peroxidation in rat pancreas in vitro.

METHODSThe free phenolics were extracted with 80% (v/v) acetone, while bound phenolics were extracted from the alkaline and acid hydrolyzed residue with ethyl acetate. Then, the interaction of the extracts with alpha-amylase and alpha-glucosidase was subsequently assessed. Thereafter, the total phenolic contents and antioxidant activities of the extracts were determined.

RESULTSThe result revealed that both extracts inhibited alpha-amylase and alpha-glucosidase in a dose-dependent manner. However, the alpha-glucosidase inhibitory activity of the extracts were significantly (P<0.05) higher than their alpha-amylase inhibitory activity. The free phenolics (31.67 mg/g) and flavonoid (17.28 mg/g) contents were significantly (P<0.05) higher than bound phenolic (23.52 mg/g) and flavonoid (13.70 mg/g) contents. Both extracts also exhibited high antioxidant activities as typified by their high reducing power, 1,1 diphenyl-2- picrylhydrazyl (DPPH) and 2, 2-azinobis-3-ethylbenzo-thiazoline-6-sulfonate (ABTS) radical scavenging abilities, as well as inhibition of Fe(2+)-induced lipid peroxidation in rat pancreas in vitro.

CONCLUSIONSThis study provides a biochemical rationale by which clove elicits therapeutic effect on type 2 diabetes.

Animals ; Antioxidants ; chemistry ; Carbohydrate Metabolism ; drug effects ; Diabetes Mellitus, Type 2 ; metabolism ; Dose-Response Relationship, Drug ; Enzyme Inhibitors ; chemistry ; pharmacology ; Ferrous Compounds ; pharmacology ; Flavonoids ; chemistry ; Glycoside Hydrolase Inhibitors ; chemistry ; pharmacology ; Inhibitory Concentration 50 ; Lipid Peroxidation ; drug effects ; Pancreas ; drug effects ; metabolism ; Phenols ; chemistry ; Plant Extracts ; chemistry ; pharmacology ; Polyphenols ; chemistry ; pharmacology ; Rats ; Syzygium ; chemistry ; alpha-Amylases ; antagonists & inhibitors ; alpha-Glucosidases

OBJECTIVEThe current study was designed to evaluate the various antioxidant potentials and inhibitory effects of phenolic-rich leaf extracts of Bridelia ferruginea (BF) on the in vitro activities of some key enzymes involved in the metabolism of carbohydrates.

METHODSIn this study, BF leaf free and bound phenolic-rich extracts were used. We quantified total phenolic and flavonoid contents, and evaluated several antioxidant activities using assays for ferric reducing antioxidant power, total antioxidant activity (phosphomolybdenum reducing ability), 1,1-diphenyl-2-picrylhydrazyl and thiobarbituric acid reactive species. Also, extracts were tested for their ability to inhibit &alpha;-amylase and &alpha;-glucosidase activity.

RESULTSThe total phenolic and total flavonoid contents in the free phenolic extract of BF were significantly greater than in the bound phenolic extract. Also, all the antioxidant activities considered were significantly greater in the free phenolic extract than in the bound phenolic extract. In the same vein, the free phenolic-rich extract had a significantly higher percentage inhibition against &alpha;-glucosidase activity (IC = 28.5 µg/mL) than the bound phenolic extract (IC = 340.0 µg/mL). On the contrary, the free phenolic extract (IC = 210.0 µg/mL) had significantly lower inhibition against &alpha;-amylase than the bound phenolic-rich extract (IC = 190.0 µg/mL).

CONCLUSIONThe phenolic-rich extracts of BF leaves showed antioxidant potentials and inhibited two key carbohydrate-metabolizing enzymes in vitro.

Animals ; Antioxidants ; chemistry ; pharmacology ; Diabetes Mellitus, Type 2 ; enzymology ; metabolism ; Enzyme Inhibitors ; chemistry ; pharmacology ; Glycoside Hydrolase Inhibitors ; chemistry ; pharmacology ; Humans ; Iron ; adverse effects ; Magnoliopsida ; chemistry ; Oxidative Stress ; drug effects ; Pancreas ; drug effects ; enzymology ; metabolism ; Phenols ; chemistry ; pharmacology ; Plant Extracts ; chemistry ; pharmacology ; Rats ; Swine ; alpha-Amylases ; antagonists & inhibitors ; chemistry ; alpha-Glucosidases ; chemistry

The present study was designed to characterize the polyphenols isolated from Acacia mearnsii bark crude extract (B) and fractions (B1-B7) obtained by high-speed counter-current chromatography (HSCCC) and evaluate their anti-inflammatory and carbolytic enzymes (α-glucosidase and α-amylase) inhibitory activities. Fractions B4, B5, B6, B7 (total phenolics 850.3, 983.0, 843.9, and 572.5 mg·g, respectively; proanthocyanidins 75.7, 90.5, 95.0, and 44.8 mg·g, respectively) showed significant activities against reactive oxygen species (ROS), nitric oxide (NO) production, and expression of pro-inflammatory genes interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS) in a lipopolysaccharide (LPS)-stimulated mouse macrophage cell line RAW 264.7. All the extracts suppressed α-glucosidase and α-amylase activities, two primary enzymes responsible for carbohydrate digestion. A. mearnsii bark samples possessed significantly stronger inhibitory effects against α-glucosidase enzyme (IC of 0.4-1.4 μg·mL) than the pharmaceutical acarbose (IC 141.8 μg·mL). B6 and B7 (IC 17.6 and 11.7 μg·mL, respectively) exhibited α-amylase inhibitory activity as efficacious as acarbose (IC 15.4 μg·mL). Moreover, B extract, at 25 µg·mL, significantly decreased the non-mitochondrial oxidative burst that is often associated with inflammatory response in human monocytic macrophages.
Acacia ; chemistry ; Animals ; Anti-Inflammatory Agents ; isolation & purification ; pharmacology ; Carbohydrate Metabolism ; drug effects ; Glycoside Hydrolase Inhibitors ; pharmacology ; Inflammation ; metabolism ; Interleukin-1beta ; metabolism ; Lipopolysaccharides ; Macrophages ; drug effects ; Mice ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Plant Bark ; chemistry ; Plant Extracts ; chemistry ; pharmacology ; Polyphenols ; isolation & purification ; pharmacology ; Proanthocyanidins ; pharmacology ; RAW 264.7 Cells ; alpha-Amylases ; antagonists & inhibitors ; alpha-Glucosidases ; metabolism

We studied the efficacy and safety of acarbose in comparison with voglibose in type 2 diabetes patients whose blood glucose levels were inadequately controlled with basal insulin alone or in combination with metformin (or a sulfonylurea). This study was a 24-week prospective, open-label, randomized, active-controlled multi-center study. Participants were randomized to receive either acarbose (n=59, 300 mg/day) or voglibose (n=62, 0.9 mg/day). The mean HbA1c at week 24 was significantly decreased approximately 0.7% from baseline in both acarbose (from 8.43% +/- 0.71% to 7.71% +/- 0.93%) and voglibose groups (from 8.38% +/- 0.73% to 7.68% +/- 0.94%). The mean fasting plasma glucose level and self-monitoring of blood glucose data from 1 hr before and after each meal were significantly decreased at week 24 in comparison to baseline in both groups. The levels 1 hr after dinner at week 24 were significantly decreased in the acarbose group (from 233.54 +/- 69.38 to 176.80 +/- 46.63 mg/dL) compared with the voglibose group (from 224.18 +/- 70.07 to 193.01 +/- 55.39 mg/dL). In conclusion, both acarbose and voglibose are efficacious and safe in patients with type 2 diabetes who are inadequately controlled with basal insulin. (ClinicalTrials.gov number, NCT00970528)
Acarbose/adverse effects/*therapeutic use ; Blood Glucose ; Diabetes Mellitus, Type 2/blood/*drug therapy ; Enzyme Inhibitors/adverse effects/therapeutic use ; Female ; Hemoglobin A, Glycosylated/analysis ; Humans ; Hypoglycemic Agents/adverse effects/therapeutic use ; Inositol/adverse effects/*analogs & derivatives/therapeutic use ; Insulin/*blood/therapeutic use ; Male ; Metformin/therapeutic use ; Middle Aged ; Prospective Studies ; alpha-Glucosidases/antagonists & inhibitors

Human maltase-glucoamylase (MGAM) hydrolyzes linear alpha-1,4-linked oligosaccharide substrates, playing a crucial role in the production of glucose in the human lumen and acting as an efficient drug target for type 2 diabetes and obesity. The amino- and carboxyl-terminal portions of MGAM (MGAM-N and MGAM-C) carry out the same catalytic reaction but have different substrate specificities. In this study, we report crystal structures of MGAM-C alone at a resolution of 3.1 Å, and in complex with its inhibitor acarbose at a resolution of 2.9 Å. Structural studies, combined with biochemical analysis, revealed that a segment of 21 amino acids in the active site of MGAM-C forms additional sugar subsites (+ 2 and + 3 subsites), accounting for the preference for longer substrates of MAGM-C compared with that of MGAM-N. Moreover, we discovered that a single mutation of Trp1251 to tyrosine in MGAM-C imparts a novel catalytic ability to digest branched alpha-1,6-linked oligosaccharides. These results provide important information for understanding the substrate specificity of alpha-glucosidases during the process of terminal starch digestion, and for designing more efficient drugs to control type 2 diabetes or obesity.
Acarbose ; chemistry ; Amino Acid Sequence ; Catalytic Domain ; Crystallography, X-Ray ; Glycoside Hydrolase Inhibitors ; Humans ; Hydrogen Bonding ; Intestines ; enzymology ; Kinetics ; Maltose ; chemistry ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Mutation, Missense ; Oligosaccharides ; chemistry ; Pichia ; Protein Binding ; Recombinant Proteins ; antagonists & inhibitors ; chemistry ; genetics ; Substrate Specificity ; Surface Properties ; alpha-Glucosidases ; chemistry ; genetics