The polyherbal formulation containing Allium sativum L., Terminalia bellirica (Gaertn.) Roxb., Curcuma aeruginosa Roxb., and Amomum compactum Sol ex. Maton has been used for hypertension treatment empirically. Our previous study showed its blood pressure-lowering effect on a rat model of hypertension. However, toxicity data were not available for this polyherbal formulation. This study is aimed at evaluating the acute and subchronic oral toxicity of the polyherbal formulation in rats. The acute toxicity study was conducted on 6 female Wistar rats using the fixed-dose method for the treatment group and 5 female Wistar rats for the control. The single dose of 2,000 mg/kg of the polyherbal formulation was given orally. There were no significant toxic effects and no death observed until the end of the study, and it was showed that the lethal dose 50% (LD50) of the polyherbal formulation was estimated to be more than 2,000 mg/kg. The macroscopic and microscopic examination of vital organs showed no symptoms of toxicity. At the subchronic toxicity study, the polyherbal formulation with 3 dose variations of 252 mg/kg, 1,008 mg/kg, and 4,032 mg/kg was administered for 91 days orally. The lowest dose of 252 mg/kg is equivalent to the daily recommended dose for a human. There were no significant toxic effects observed at all doses on physical sign and symptoms, weight gain, food intake, hematological parameters, biochemical parameters, and macroscopic and microscopic examination of organs. These findings showed that the short- and long-term oral administration of the polyherbal formulation is safe to use within its dose recommendation.

Purpose: To investigate the antiplasmodial and onset of growth inhibitory activities of T. diversifolia fractions against Plasmodium falciparum FCR3 strain. Methods: Seven fractions of T. diversifolia (F1-F7) were used in this study. Phytochemical analysis was conducted to identify the major compounds in the fractions. Various concentrations of fractions ranging from 2.5-100.0 µg/mL were exposed to P. falciparum FCR3 strain for 60 h and the growth inhibition was then calculated. The fraction which exhibited the best antiplasmodial activity was tested further to determine the growth inhibition onset against P. falciparum FCR3 strain. This was achieved by examining the inhibitory activity of the fraction when it was added at the beginning of the experiment and assessing subsequent parasite growth after 8, 16, 24, 32, and 40 h incubation. Results: The major compounds found in the fractions were terpenes. Fraction six (F6) had the best antiplasmodial activity (IC50 13.63 ± 1.43 µg/mL). During the first 32 h of incubation, F6 inhibited the growth of parasites and this increased with longer incubation time; 32 h incubation provided the highest growth inhibition (99.23 ± 0.05 %). After 32 h the inhibition activity began to decrease, and resulted in < 50 % inhibition at 48 h incubation. This result suggested that F6 is a rapid-onset antiplasmodial agent. Conclusion: Fractions of T. diversifolia, especially F6, are promising antimalarial agents and require further development for clinical application.

The pharmacokinetics of diclofenac after a single oral dose (50 mg) were studied in 10 healthy adults on two occasions separated by 2 weeks, once in the morning (dose administered at 07.00 h) and once in the evening (dose at 19.00 h). Peak serum drug concentrations as well as the area under the drug concentration-time curve were significantly less during the night compared with the day (Cmax: 1886 ± s.d. 901 vs 2791 ± 1565 ng ml-1 and AUC: 2807 ± 1376 vs 3681 ± 1986 ng ml-1 h). However, the time to reach peak concentration (tmax) and the half-life of diclofenac (t½/2) were not significantly different on the two occasions. We suggest that the extent of diclofenac absorption is slightly lower following administration in the evening compared with administration in the morning.

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An indole alkaloid with aspidospemane structure possessing a potential antiplasmodial activity, vincadifformine, has been isolated from Aspidosperma pyrifolium Mart. Moreover, 10 derivatives were prepared from the vincadifformine. The study was conducted to evaluate the in vitro antiplasmodial and cytotoxic activity of the vincadifformine and their semisynthetic derivatives. The in vitro antiplasmodial activity was evaluated on Plasmodium falciparum chloroquine-resistant (FcM ) and -sensitive (Nigerian) strains after 24-h and 72-h incubation, the CI of two compounds were also lower after 24-h incubation (CI, 2.0 and 4.8) than that of after 72-h incubation (CI, 9.5 and 11.5). Further study will be conducted to evaluate quantitative structure-activity relationship (QSAR) in order to design new antimalarial drugs.