Ginkgo biloba has a very high medicinal value. The flavonol glycosides and terpene lactones contained in G. biloba extract (GBE) have such pharmacological effects as antioxidant, anti-platelet aggregation and memory improvement, enhancement of immune function. However, the ginkgolic acid (GA) contained in GBE is proved to be highly allergenic and cytotoxic, even minimal residual could also cause severe adverse effects. To minimize the potential safety hazards of ginkgo leaf preparations, this study focuses on GA's chemical structure, adverse effects, toxicity and genesis mechanism, desorption and attenuation in the hope of providing a new thought for studies on safety of Ginkgo biloba preparations.
Animals ; Ginkgo biloba ; chemistry ; Humans ; Salicylates ; adverse effects ; pharmacology ; toxicity

AIMNineteen compounds related to salicylic acid were evaluated for their in vitro activity of inhibiting beta-lactamase isolated from a resistant strain of Pseudomonas aeruginosa, and their structure-activity relationships were examined.

METHODSNitrocefin method was used.

RESULTSThe 50% inhibitory concentration (IC50) of salicylic acid inhibiting beta-lactamase was 22 mmol x L(-1); four analogs had IC50 lower than that of salicylic acid; fifteen analogs had IC50 higher than that of salicylic acid.

CONCLUSIONExamination of the structure-activity relationships of the compounds revealed that carboxyl group and adjoining hydroxyl group were active group, and replacement of adjoining hydroxyl by carboxyl increased activity nearly 4-fold. Moreover, addition of a sulfonic group at C-5 and nitro group at C-3, 5 of benzenoic ring of salicylic acid resulted in a 2-fold to 3-fold increase in activity, addition of a amino group at C-5 of benzenoic ring of salicylic acid decreased activity, add addition of -Cl or -F at C-2,4 position of benzenoic ring of benzoic acid did not show activity.

Anti-Bacterial Agents ; chemical synthesis ; chemistry ; pharmacology ; Cephalosporins ; metabolism ; Inhibitory Concentration 50 ; Pseudomonas aeruginosa ; enzymology ; Salicylates ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship ; beta-Lactamases ; isolation & purification ; metabolism

The latest progress in research on constituents and pharmacological activities of sarcotestas of Ginkgo biloba has been studied. The main constituents in sarcotestas of G. biloba include flavones, ginkgolides, alkylphenols, polysaccharides and amino acids, etc. They show the following activities, such as bacteriostatic, bactericidal and pesticidal activities, antitumor and mutagenic, carcinogenic effects, antianaphylaxis and allergenic activity, effects on immunologic function, scavenging free radical, antisenile action, etc. The problems at present and the reseach direction for the future on sarcotestas of G. biloba have been put forward.
Animals ; Anti-Bacterial Agents ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Flavonoids ; analysis ; isolation & purification ; pharmacology ; Free Radical Scavengers ; pharmacology ; Fruit ; chemistry ; Ginkgo biloba ; chemistry ; Ginkgolides ; analysis ; isolation & purification ; pharmacology ; Humans ; Plants, Medicinal ; chemistry ; Salicylates ; analysis ; isolation & purification ; pharmacology

Glucokinase (GK) is a new target for the treatment of type II diabetes mellitus (T2DM). In order to find a structure-simplified small molecule GK activator, 19 salicylic acid derivatives were designed and synthesized based on new lead compound (1). Experimental results showed that the potency of compound 8h is superior to control RO-28-0450 in GK activation.
Drug Design ; Enzyme Activation ; drug effects ; Enzyme Activators ; chemical synthesis ; chemistry ; pharmacology ; Glucokinase ; metabolism ; Hypoglycemic Agents ; chemical synthesis ; chemistry ; pharmacology ; Molecular Structure ; Salicylates ; chemical synthesis ; chemistry ; pharmacology ; Thiazoles ; pharmacology

OBJECTIVETo study the method for synthesis of 2-hydroxyl-5- butyramidobenzoic acid and test its effect on acetic acid-induced colitis in rats.

METHODS2-hydroxyl-5-butyramidobenzoic acid was synthesized from 5-aminosalicylic acid and butyric acid by amidation, esterification and hydrolization. The effect of 2-hydroxyl-5-butyramidobenzoic acid on acetic acid enema-induced colitis in rats was investigated.

RESULTSThe structure of 2-hydroxyl-5-butyramidobenzoic acid was identified by IR and 1H-NMR. After treatment with acetic acid, the colon mucosal damage index (CMDI), fecal occult blood (OB) test, and activity of myelperoxidase (MPO) increased significantly in the rats as compared to the control levels. 2-hydroxyl-5- butyramidobenzoic acid obviously reduced the CMDI and OB, and reduced the level of MPO in the rats with colitis.

CONCLUSIONThe synthesis of 2-hydroxyl-5-butyramidobenzoic acid requires only mild conditions with simple procedures, and the synthesized 2-hydroxyl-5-butyramidobenzoic acid shows obvious therapeutic effects on mucosal damage of in rats with acetic acid-induced colitis.

Acetic Acid ; Aminobenzoates ; chemical synthesis ; chemistry ; pharmacology ; therapeutic use ; Animals ; Colitis, Ulcerative ; chemically induced ; drug therapy ; Male ; Protective Agents ; chemical synthesis ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Salicylates

The permeability of cell membrane was enhanced by exogenous SA in the culture of Taxus cuspidata. Nuclei condense and fragments were observed in some cells by using fluorescent microscope, and the degraded chromosomal DNA was observed by using agarose gel electrophoresis. The changes in soluble proteins of the suspension cultures of Taxus cuspidata induced by salicylic acids were analyzed by using two-dimensional polyacrylamide gel electrophoresis. Comparing with the control, seven new protein spots were found and six protein spots were not found in the cultures grown with SA at 48h. The results obtained showed that SA could induce the expression of some special proteins that might be related with the action of SA in the suspension cultures of Taxus cuspidata.
Cell Culture Techniques ; methods ; DNA, Plant ; genetics ; Electrophoresis, Agar Gel ; Electrophoresis, Gel, Two-Dimensional ; methods ; Gene Expression Regulation, Plant ; drug effects ; Plant Proteins ; genetics ; metabolism ; Salicylates ; pharmacology ; Taxus ; genetics ; metabolism

Use of genetically engineered microorganisms (GEMs) for pollution abatement has been limited because of the risks associated with their uncontrolled release in environment. In this study, a pollutant-dependent bacterial containment system was constructed in E. coli JM109. The system consisted of two plasmids containing a killing element and a regulatory element respectively. The survival of strains can be regulated by the concentration of salicylate in environment. In the presence of salicylate, the expression of the suicide gene gef was inhibited with the synthesis of LacI protein, leading to the normal proliferation of the strain. While in the absence of salicylate, the expression of the regulatory element was cancelled, and the expression of the suicide gene gefled to a high rate of cell killing. This containment system can be used as a model during the construction of genetically engineered strains for bioremediation.
Biodegradation, Environmental ; Containment of Biohazards ; methods ; Environmental Pollutants ; metabolism ; Escherichia coli ; genetics ; metabolism ; Gene Expression Regulation, Bacterial ; Genes, Bacterial ; Genes, Lethal ; genetics ; Genetic Engineering ; methods ; Organisms, Genetically Modified ; genetics ; metabolism ; Salicylates ; pharmacology

OBJECTIVETo understand what role of the transient outward potassium channels and the delayed rectifier potassium channels play in the mechanism of salicylate-induced tinnitus.

METHODSThe effects of salicylate on the transient outward potassium channels and the delayed rectifier potassium channels in freshly dissociated inferior colliculus neurons of rats were studied, using the whole-cell voltage clamp method.

RESULTSSalicylate blocked the transient outward potassium current (I(K(A and the delayed rectifier potassium current (I(K(DR in concentration-dependent manner (0.1-1 mmol/L). The IC50 values for the blocking action of salicylate on I(K(A)) and I(K(DR)) were 2.27 and 0.80 mmol/L, respectively. At a concentration of 1 mmol/L, salicylate did not shift the activation and inactivation curves of I(K(A)), but significantly shifted the activation and inactivation curves of I(K(DR)) negatively by approximately 11 mV and 24 mV.

CONCLUSIONSSalicylate inhibits both I(K(A)) and I(K(DR)) in rat inferior colliculus neurons but only significantly affects the activation and inactivation kinetics of I(K(DR)). Effects of I(K(A)) and I(K(DR)), especially I(K(DR)), by salicylate may play an important role in salicylate-induced tinnitus.

Animals ; Delayed Rectifier Potassium Channels ; drug effects ; Inferior Colliculi ; cytology ; drug effects ; Male ; Neurons ; drug effects ; physiology ; Patch-Clamp Techniques ; Potassium Channels ; drug effects ; physiology ; Rats ; Rats, Wistar ; Salicylates ; pharmacology

Nonsteroidal antiinflammatory drugs(NSAIDs) are known as clinically effective agents for treatment of inflammatory diseases. Inhibition of cyclooxygenase has been thought to be a major facet of the pharmacological mechanism of NSAIDs. However, it is difficult to ascribe the antiinflammatory effects of NSAIDs solely to the inhibition of prostaglandin synthesis. Human neutrophil elastase (HNElastase; HNE, EC 3.4.21.37) has been known as a causative factor in inflammatory diseases. To investigate the specific relationship between HNElastase inhibition and specificity of molecular structure of several NSAIDs, HNElastase was purified by Ultrogel AcA54 gel filtration, CM-Sephadex ion exchange, and HPLC (with TSK 250 column) chromatography. HNElastase was inhibited by aspirin and salicylate in a competitive manner and by naproxen, ketoprofen, phenylbutazone, and oxyphenbutazone in a partial competative manner, but not by ibuprofen and tolmetin. HNElastase-phenylbutazone-complex showed strong Raman shifts at 200, 440, 1124, 1194, 1384, 1506, and 1768 cm(-1). The Raman bands 1194, 1384, and 1768 cm(-1) may represent evidences of the conformational change at -N=N-phi radical, pyrazol ring, and -C=O radical of the elastase-drug complex, respectively. Phenylbutazone might be bound to HNElastase by ionic and hydrophobic interaction, and masked the active site. Inhibition of HNElastase could be another mechanism of action of NSAIDs besides cyclooxygenase inhibition in the treatment of inflammatory diseases. Different inhibition characteristics of HNE-lastase by NSAIDs such as aspirin, phenylbutazone-like drugs and ineffective drugs could be important points for drawing the criteria for appropriate drugs in clinical application.
Anti-Inflammatory Agents, Non-Steroidal/pharmacology* ; Chromatography, Affinity ; Computer Simulation ; Enzyme Inhibitors/pharmacology ; Human ; Isoenzymes/isolation & purification ; Isoenzymes/antagonists & inhibitors ; Ketoprofen/pharmacology ; Leukocyte Elastase/isolation & purification ; Leukocyte Elastase/antagonists & inhibitors* ; Models, Molecular ; Naproxen/pharmacology ; Phenylbutazone/analogs & derivatives ; Salicylates/pharmacology ; Spectrum Analysis, Raman

To prepare the derivatives of salicylic acid-g-chitosan and study their synergistic and complementary actions, the synergism of anti-inflammatory action of the derivatives was investigated with the experiments of xylene-induces mice ear edema, the analgesic activities by the tartaric emetic-induced mice twist test and the hot-plate test, and the complementary effects between salicylic acid and chitosan through morphological changes of stomach mucous membrane of rat, separately. The anti-inflammatory activities of salicylic acid-g-chitosan derivatives for anti-inflammatory activities were more potent than that of salicylic acid and chitosan and dexamethasone cream in external use, and more potent than that of aspirin orally. However, immediate analgesic activity of the derivatives was lower than that of aspirin and persistent activity was similar as that of aspirin. And the stomach mucous membrane morphology change of the derivatives was much milder than that of aspirin. The salicylic acid grafted chitosan derivatives showed synergistic and complementary effect on the anti-inflammatory and analgesic activities and so on.
Analgesics ; adverse effects ; chemical synthesis ; pharmacology ; Animals ; Anti-Inflammatory Agents ; adverse effects ; chemical synthesis ; pharmacology ; Chitosan ; adverse effects ; analogs & derivatives ; chemical synthesis ; pharmacology ; Drug Synergism ; Edema ; chemically induced ; drug therapy ; Female ; Gastric Mucosa ; drug effects ; Male ; Mice ; Pain Measurement ; Pain Threshold ; drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Salicylates ; adverse effects ; chemical synthesis ; pharmacology