Antipyretic, analgesic and anti-oxidative activities of Aquilaria crassna leaves extract in rodents.

In Thailand, the leaves of Aquilaria crassna have been used traditionally for the treatments of various disorders, but without any scientific analysis. In this study, the antipyretic, analgesic, anti-inflammatory and anti-oxidative properties of A. crassna leaves extract were investigated at a wide dose range in rodents. Experimental animals were treated orally with an aqueous extract of Aquilaria crassna leaves (ACE). They were tested for antipyretic (Baker's yeast-induced fever in rats), analgesic (hot plate test in mice) and anti-inflammatory (carrageenan-induced paw edema in rats) activities. An anti-oxidative effect of ACE was evaluated by using the DPPH anti-oxidant assay. The results showed that, after 5 hours of yeast injection, 400 and 800 mg/kg ACE significantly reduced the rectal temperature of rats. Mice were found significantly less sensitive to heat at an oral dose of 800 mg/kg ACE, after 60 and 90 min. No anti-inflammatory activity of ACE at an 800 mg/kg dose could be observed in the rat paw assay. An anti-oxidative activity of ACE was observed with an IC (50)value of 47.18 µg/ ml. No behavioral or movement change could be observed in mice after oral administration of ACE (800 or 8,000 mg/kg) for seven consecutive days. Interestingly, from the second day of treatment, animals had a significant lower body weight at the 8,000 mg/kg dose of ACE compared to the control. No toxicity was identified and the results of this study state clearly that Aquilaria crassna leaves extracts possess antipyretic, analgesic and anti-oxidative properties without anti-inflammatory activity.

In vivo evaluation of substituted 3-amino-1,4-benzodiazepines as anti-depressant, anxiolytic and anti-nociceptive agents.

Oxazepam (CAS 604-75-1) 4a served as building block in the synthesis of substituted 3-amino-1,4-benzodiazepines, which were subsequently tested in various CNS animal models. The hydroxy group of oxazepam was either activated as a chloride (Method A) or as a phosphor-oxy derivative (Method B) giving the desired 3-amino-1,4-benzodiapines 6a-6r in high yields with primary and secondary amines in a typical nucleophilic substitution reaction. Eighteen 3-substituted 1,4-benzodiazepines were prepared and served as new chemical entities and for lead structure discovery. The mixed cholecystokinin (CCK) antagonist 6e showed anxiolytic and antidepressant effects from 10 microg/kg in mice in the elevated x-maze test and the forced swimming test. The CCK1 antagonist 6 g has shown antidepressant effects from the same dose, but lacked anxiolytic properties. Both compounds potentiated at a dose of 0.5 mg/kg morphine antinociception with a maximum possible effect (MPE) about 35%. By assessing initially the MPE of antinocipection for the 18 newly synthesised benzodiazepines in the tail-flick test, 4 other benzodiazepines were found active. In further in vive evaluation the cyclohexyl derivative 6 i displayed anxiolytic, antidepressant and antinociceptive properties as single agent at a dose of 5 mg/kg without toxicity. The benzodiazepines 6i and 6p, which initially showed a higher MPE in terms of morphine potentiation (43/44%) showed analgesic effects as single agents, without having anxiolytic or antidepressant properties. The amino-piperidinyl derivative 6p displayed a similar dose-response relationship to morphine, but was 3 times more potent.

Effect of aloe (Aloe vera Linn.) on healthy adult volunteers: changes in urinary composition.

OBJECTIVE: 1. To investigate the amount of citrate and tartrate in aloe gel, and in the urine of healthy normal volunteers, before and after consuming fresh aloe gel. 2. To evaluate the changes in the chemical composition of urine among subjects after taking aloe gel. 3. To determine the value of consuming aloe gel for prevention of renal stone formation. DESIGNS: Experimental study; before and after experiment with no control group MATERIAL AND METHOD: Thirty one healthy male medical students between 18 and 23 years of age were enrolled (with informed consent) in the clinical trial. Subjects ingested 100 g of fresh aloe gel twice a day for seven consecutive days. The 24-hr urine was collected one day prior to taking the gel (Day 0), Days 2 and 5 of consumption, and Day 8 (one day after completion). The authors determined the urine volume, osmolality, potassium, sodium, phosphate, calcium, magnesium, uric acid, citrate, tartrate, oxalate, Permissible Increment in calcium (PI in calcium), Permissible Increment in oxalate (PI in oxalate), Concentration product ratio of calcium phosphate (CPR of CaPO4) and the citrate per creatinine ratio. RESULTS: The citrate and tartrate concentration in 100 g of fresh aloe gel was 96.3 and 158.9 mg, respectively. The urinary excretion of oxalate was significantly decreased (p < 0.05). The PI in calcium was significantly increased (p < 0.05), while the citrate excretion and PI in oxalate were consistently, albeit non-significantly, increased. The mean CPR values of CaPO4 were decreased non-significantly. The other measurements were unremarkable. CONCLUSION: Fresh Aloe vera gel (100 g) contains 96.3 mg of citrate and 158.9 mg of tartrate. This is mid-range for Thai fruits. Changes in chemical compositions of urine after aloe consumption shows its potential for preventing kidney stone formation among adults.

Changes in urinary compositions among children after consuming prepared oral doses of aloe (Aloe vera Linn).

OBJECTIVES: 1) To investigate the amount of citrate and tartrate in aloe gel, and in the urine of healthy normal children, before and after consuming fresh aloe gel. 2) To evaluate the changes in the chemical composition of urine among subjects after taking aloe gel. 3) To determine the value of consuming aloe gel for prevention of renal stone formation. DESIGN: Experimental study. MATERIAL AND METHOD: Thirteen healthy boys between 9 and 13 years of age were enrolled (with informed permission) in the clinical trial. Subjects ingested 100 g of fresh prepared aloe gel twice a day for seven consecutive days. The 24-hour urine was collected one day prior to taking the gel (Day 0), Days 2 and 5 of consumption, and Day 8 (one day after completion). The authors determined the urine volume, osmolality, potassium, sodium, phosphate, calcium, magnesium, uric acid, citrate, tartrate, oxalate, Permissible Increment in Calcium (PI Ca), Permissible Increment in Oxalate (PI Ox), Concentration Product Ratio of Calcium Phosphate (CPR CaPO4) and the citrate per creatinine ratio. RESULTS: The citrate and tartrate concentration in 100 g of fresh aloe gel was 96.3 and 158.9 mg, respectively. The 24-hr urine volume and urinary citrate excretion were significantly increased (p < 0.05). The PI Ca and the PI Ox were also significantly increased (p < 0.05). The other measurements were unremarkable. CONCLUSION: One hundred grams of fresh Aloe vera gel contains 96.3 milligrams of citrate and 158.9 milligrams of tartrate and were in the mid-range among Thai fruits. Changes in chemical compositions of urine after aloe gel consumption shows potential for preventing kidney stone formation among children.

Synthesis and evaluation of N1-substituted-3-propyl-1,4-benzodiazepine-2-ones as cholecystokinin (CCK2) receptor ligands.

A novel synthetic approach towards N1-alkylated 3-propyl-1,4-benzodiazepines was developed in five synthetic steps from 2-amino-4-chlorobenzophenone, in which the N-oxide 4 served as a key intermediate. The structure-activity relationship optimization of this 3-propyl-1,4-benzodiazepine template was carried out on the N1-position by selective alkylation reactions and resulted in a ligand with an improved affinity on the cholecystokinin (CCK2) receptor. The N-allyl-3-propyl-benzodiazepine 6d displayed an affinity towards the CCK2 (CCK-B) receptor of 170 nM in a radiolabelled receptor-binding assay. The anxiolytic activity of this allyl-3-propyl-1,4-benzodiazepine 6d was subsequently determined in in-vivo psychotropic assays. This novel ligand had ED50 values of 4.7 and 5.2 mg kg(-1) in the black and white box test and the x-maze, respectively, and no significant sedation/muscle relaxation was observed.