OBJECTIVETo study the inhibitory activity of Aeschynanthus maculatus on alpha-glucosidase.

METHODThe inhibilitory model of in vitro alpha-glucosidase was established. Active extracts of A. maculatus were isolated and identified bymultiple chromatographic methods, and their molecular structures were identifiied by spectral techniques.

RESULTSeven coumpounts were isolated from A. maculatus and isolated as lupeol(1), stigmasterol(2), ursolic acid(3), stigmast-5,22(E)-diene-3beta-ol(4), beta-daucosterol(5), 3-hydroxy-12-taraxasten-28-oic-acid(6) and oleanic acid(7). Compounds 1 (IC50 25.41 mg x L(-1)),3(IC0 4.42 mg L(-1)),4(IC50 11.50 mg x L(-1)),6(IC50 14.17 mg x L(-1)) and 7(IC50 2.88 mg x L(-1)) had higher inhibitory activities than that of acarbose (IC50 1103.01 mg x L(-1)) as the positive control drug.

CONCLUSIONCompound 1-7 were isolated from this plant for the first time. Compound 6 was isolated from Gesneriaceae family for the first time. Compound 7 was isolated from Aeschynanthus genus for the first time.

Enzyme Inhibitors ; chemistry ; pharmacology ; Ferns ; chemistry ; Glycoside Hydrolase Inhibitors ; Plant Exudates ; chemistry ; pharmacology

OBJECTIVETo investigate the effect of Angelicae Pubescentis Radix (APR) on the activity of endocannabinoid hydrolase and N-acylethanolamine-hydrolyzing acid amidase (NAAA), and to demonstrate the mechanism of anti-inflammatory effect of APR by in vitro lipopolysaccharide (LPS)-induced inflammation model.

METHODAPR essential oil was extracted by steam distillation, and the chemical components were identified by GC-MS. Enzymatic activity was performed by using recombinant NAAA-overexpressing protein and detected by LC-MS. Lipids were extracted by methonal/chloroform mixure and analyzed by LC-MS. mRNA and protein expression levels of proinflammatory genes were examined by Real time-PCR and ELISA assay kit, respectively. The content of nitro oxide (NO) was detected by Griess reaction.

RESULTTwenty active components were identified from APR essential oil which inhibited NAAA activity in a dose-dependent manner. On the LPS-induced RAW264.7 cells, APR essential oil reversed LPS-suppressed N-palmitoylethanolamide (PEA) contents in a dose-dependent manner and reduced LPS-induced proinflammatory genes, TNF-alpha and IL-6. Moreover, APR essential oil reduced the mRNA expression of iNOS, subsequently reduced the release of NO, a classic inflammatory marker.

CONCLUSIONThe research demonstrated that the effect of APR on inflammation is mediated by the inhibition of NAAA activity, which increase the cellular endobioactor PEA levels and decrease proinflammatory factor. The results suggest that APR can serve as a nature NAAA inhibitor.

Amidohydrolases ; antagonists & inhibitors ; Angelica ; chemistry ; Animals ; Anti-Inflammatory Agents ; pharmacology ; Enzyme Inhibitors ; pharmacology ; Lipopolysaccharides ; pharmacology ; Mice ; Oils, Volatile ; analysis ; pharmacology

This article summarized the chemical construction and plant resources, biochemical and pharmacologicaly activity and the anti-oxygenation effect of procyanidins.
Animals ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Antimutagenic Agents ; pharmacology ; Antioxidants ; pharmacology ; Enzyme Inhibitors ; pharmacology ; Humans ; Plants, Medicinal ; chemistry ; Platelet Aggregation Inhibitors ; pharmacology ; Proanthocyanidins ; chemistry ; isolation & purification ; pharmacology

Two new dimeric naphthoquinones, 5',8'-dihydroxy-6,6'-dimethyl-7,3'-binaphthyl-1,4,1',4'-tetraone (1; Di-naphthodiospyrol D) and 5',8'-dihydroxy-5,8-dimethoxy-6,6'-dimethyl-7,3'-binaphthyl-1,4,1',4'-tetraone (2; Di-naphthodiospyrol E), along with known naphthoquinones diospyrin (3) and 8-hydroxy diospyrin (4) were isolated from the chloroform fraction of extract of Diospyros lotus roots. Their structures were elucidated by advanced spectroscopic analyses, including HSQC, HMBC, NOESY, and J-resolved NMR experiments. The fractions and compounds 1-4 were evaluated for urease activity and phosphodiesterase-I, carbonic anhydrase-II and α-chymotrypsin enzyme inhibitory activities. Compounds 1 and 2 and their corresponding fractions showed significant and selective inhibitory effects on urease activities. The IC values of 1 and 2 were 260.4 ± 6.37 and 381.4 ± 4.80 µmol·L, respectively, using thiourea (IC = 21 ± 0.11 µmol·L) as the standard inhibitor. This was the first report demonstrating that the naphthoquinones class showed urease inhibition.
Biological Assay ; Diospyros ; chemistry ; Enzyme Inhibitors ; chemistry ; isolation & purification ; pharmacology ; Molecular Structure ; Naphthoquinones ; chemistry ; isolation & purification ; pharmacology ; Plant Extracts ; chemistry ; pharmacology ; Plant Roots ; Urease ; antagonists & inhibitors

OBJECTIVETo provide a scientific basis for the drug-combination and aim to examine whether astragaloside IV has the impact on the cytochrome P450 enzymes.

METHODTolbutamide, chlorzoxazone, coumarin, nifedipine, and phenacetin were as probe substrates of rat CYP2C9, CYP2E1, CYP2A6, CYP3A4, and CYP1A2, and were incubated in rat liver microsomes with astragaloside IV. Triplicate samples were run to generate IC50 value by incubating P450 probe substrates in the presence of five concentrations of astragaloside IV in the incubation mixture. The K(i) values were determined by fitting the probe substrate at various inhibitor concentrations to the equations for competitive inhibition, noncompetitive inhibition, noncompetitive inhibition, and mixed-type inhibition.

RESULTIC50 and K(i) values were estimated, and the types of inhibition were determined. Among the five probe substrates, astragaloside IV might not significantly affect CYP2E1, CYP2A6 and CYP1A2-mediated metabolism in rats, but was a competitive inhibitor of CYP2C9 (IC50 35.40 micromol x L(-1), K(i) 42.88 micromol x L(-1)), and was a uncompetitive inhibitor of CYP3A4 (IC50 88.24 micromol x L(-1), K(i) 33.31 micromol x L(-1)).

CONCLUSIONThese results suggested that astragaloside IV inhibited CYP2C9 and CYP3A4, which provided useful information for safe and effective use of astragaloside IV.

Animals ; Cytochrome P-450 Enzyme Inhibitors ; Cytochrome P-450 Enzyme System ; chemistry ; metabolism ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Enzyme Inhibitors ; chemistry ; pharmacology ; Kinetics ; Male ; Microsomes, Liver ; chemistry ; drug effects ; enzymology ; Rats ; Rats, Sprague-Dawley ; Saponins ; pharmacology ; Triterpenes ; pharmacology

Twelve compounds were isolated from Psoralea corylifolia and their structures were identified as isopsoralen (1), psoralen (2), 8-methoxypsoralen (3), psoralidin (4), corylin (5), bavachin (6), daidzein (7), corylifolinin (8), bavachinin (9), neobavaisoflavone (10), daidzin (11) and astragalin (12). The results showed that psoralidin had the activity of scavenging DPPH free radicals activity (IC50 43.85 mg x L(-1)). Psoralidin (IC50 1.32 mg x L(-1))c, oryfolin (IC50 4.97 mg x L(-1)), daidzin (IC50 10.47 mg x S(-1)), daidzein (IC50 34.22 mg) x L(-1)) and astragalin (IC50 31.27 mg x L(-1)) had the activity of scavenging ABTS free radical. Psoralidin (IC50 40.74 mg x L(-1)), coryfolin (IC50 45.73 mg x L(-1)) and daidzein (IC50 49.44 mg x L(-1)) had alpha-glucosidase inhibitory activity. Corylifolinin and neobavaisoflavone had significantly effect of inhibiting SA, MRSA and ESBLs-SA (MIC 0. 781 3, 1.562, 5, 0.781 25 microg x disc(-1) and 6.25, 6.25, 6.25 microg x disc(-1).
Anti-Infective Agents ; chemistry ; pharmacology ; Antioxidants ; chemistry ; pharmacology ; Bacteria ; drug effects ; Enzyme Inhibitors ; chemistry ; pharmacology ; Free Radical Scavengers ; chemistry ; pharmacology ; Glycoside Hydrolase Inhibitors ; Inhibitory Concentration 50 ; Plant Extracts ; chemistry ; pharmacology ; Plants, Medicinal ; chemistry ; Psoralea ; chemistry

AIMTo evaluate the effect of paeonol on the activity of tyrosinase and provide experimental evidence for the treatment of hyperpigmentation disorders.

METHODSTyrosinase activity was estimated by measuring the oxidation rate of L-3,4-dihydroxyphenylalanine (L-Dopa). The inhibitory effects of paeonol on the activity of mushroom tyrosinase and Michaelis-Menten kinetics were deduced from the Lineweaver-Burk plots.

RESULTSThe inhibitory concentration of paeonol leading to 50% enzyme activity lost (IC50) was estimated to be 0.60 mmol x L(-1). The inhibition constants for paeonol binding free enzyme, K(I), and substrate-enzyme, K(IS), are 0.084 and 0.12 mmol x L(-1), respectively.

CONCLUSIONPaeonol is a potential mixed inhibitor of mushroom tyrosinase. The mixed inhibition function may originate from its ability to form a Schiff base with a primary amino group and to chelate copper at the active site of tyrosinase.

Acetophenones ; isolation & purification ; pharmacology ; Enzyme Inhibitors ; pharmacology ; Kinetics ; Levodopa ; metabolism ; Monophenol Monooxygenase ; metabolism ; Paeonia ; chemistry ; Plants, Medicinal ; chemistry

Histone deacetylase (HDAC) has been highlighted as one of key players in tumorigenesis and angiogenesis. Recently, several derivatives of psammaplin (Psams) from a marine sponge have been known to inhibit the HDAC activity, but the molecular mechanism for the inhibition has not fully understood. Here, we explored the mode of action of Psams for the inhibition of HDAC activity in the molecular and cellular level. Among the derivatives, psammaplin A (Psam A) showed the potent inhibitory activity in enzyme assay and anti-proliferation assay with IC50 value of 0.003 and 1 microM, respectively. Psam A selectively induced hyperacetylation of histones in the cells, resulting in the upregulation of gelsolin, a well-known HDAC target gene, in a transcriptional level. In addition, reduced Psam A showed a stronger inhibitory activity than that of non-reduced one. Notably, glutathione-depleted cells were not sensitive to Psam A, implying that cellular reduction of the compound is responsible for the HDAC inhibition of Psam A after uptake into the cells. Together, these data demonstrate that Psam A could exhibit its activity under the reduced condition in the cells and be a new natural prodrug targeting HDAC.
Tyrosine/*analogs & derivatives/chemistry/pharmacology ; Prodrugs/chemistry/*pharmacology ; Oxidation-Reduction ; Molecular Structure ; Humans ; Histones/metabolism ; Histone Deacetylases/*antagonists & inhibitors/*classification/genetics/metabolism ; Hela Cells ; Enzyme Inhibitors/chemistry/*pharmacology ; Disulfides/chemistry/*pharmacology ; Cell Proliferation ; Biological Products/chemistry/*pharmacology ; Acetylation

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 search alpha-glucosidase inhibitors from Rubia cordifolia.

METHODThe alpha-glucosidase inhibitors were isolated by the column chromatographic techniques and the bioassay-guided method in vitro. A combination of MS and NMR spectroscopy was used to identify the chemical structures. The inhibitory kinetics of the inhibitors were also investigated.

RESULTThe chloroform extract showed high inhibitory activity, and three active compounds were isolated and identified as 1,3-dihydroxy-2-methylanthraquinone (1), 1-hydroxy-2-methylanthraquinone (2) and 1,2-dihydroxyanthraquinone (3). The IC5o values of compound 1-3 were all lower than that of acarbose. Compound 1 and 2 shown competitive type manner on alpha-glucosidase, whereas compound 3 shown noncompetitive type model.

CONCLUSIONCompounds 1-3 as strong inhibitors of alpha-glucosidase were reported for the first time.

Binding, Competitive ; Enzyme Inhibitors ; analysis ; metabolism ; pharmacology ; Glycoside Hydrolase Inhibitors ; Inhibitory Concentration 50 ; Kinetics ; Rubia ; chemistry ; alpha-Glucosidases ; metabolism