Safety assessment of methanol extract of red dragon fruit (Hylocereus polyrhizus): acute and subchronic toxicity studies.

Recently, the fruits of Hylocereus polyrhizus, known as red dragon fruit, have received much attention from growers worldwide. However, there is little toxicological information regarding the safety of repeated exposure to these fruits. The present study evaluated the potential toxicity of a methanol extract of H. polyrhizus fruit after acute and subchronic administration in rats. In the acute toxicity study, single doses of fruit extract (1250, 2500 and 5000 mg/kg) were administered to rats by oral gavage, and the rats were then monitored for 14 days. In the subchronic toxicity study, the fruit extract was administered orally to rats at doses of 1250, 2500 and 5000 mg/kg/day for 28 days. There was no mortality or signs of acute or subchronic toxicity. There was no significant difference in body weight, relative organ weight or hematological parameters in the subchronic toxicity study. Biochemical analysis showed some significant changes, including creatinine, globulin, total protein and urea levels. No abnormality of internal organs was observed between treatment and control groups. The lethal oral dose of the fruit extract is more than 5000 mg/kg and the no-observed-adverse-effect level (NOAEL) of the extract for both male and female rats is considered to be 5000 mg/kg per day for 28 days.

Development of a stepping force analgesic meter for a rat arthritic model.

Behavioural assessment of experimental pain is an essential method for analysing and measuring pain levels. Rodent models, which are widely used in behavioural tests, are often subject to external forces and stressful manipulations that cause variability of the parameters measured during the experiment. Therefore, these parameters may be inappropriate as indicators of pain. In this article, a stepping-force analgesimeter was designed to investigate the variations in the stepping force of rats in response to pain induction. The proposed apparatus incorporates new features, namely an infrared charge-coupled device (CCD) camera and a data acquisition system. The camera was able to capture the locomotion of the rats and synchronise the stepping force concurrently so that each step could be identified. Inter-day and intra-day precision and accuracy of each channel (there were a total of eight channels in the analgesimeter and each channel was connected to one load cell and one amplifier) were studied using different standard load weights. The validation studies for each channel also showed convincing results whereby intra-day and inter-day precision were less than 1% and accuracy was 99.36-100.36%. Consequently, an in vivo test was carried out using 16 rats (eight females and eight males). The rats were allowed to randomly walk across the sensor tunnel (the area that contained eight channels) and the stepping force and locomotion were recorded. A non-expert, but from a related research domain, was asked to differentiate the peaks of the front and hind paw, respectively. The results showed that of the total movement generated by the rats, 50.27 ± 3.90% in the case of the male rats and 62.20 ± 6.12% in that of the female rats had more than two peaks, a finding which does not substantiate the assumptions made in previous studies. This study also showed that there was a need to use the video display frame to distinguish between the front and hind paws in the case of 48.80 ± 4.01% of the male rats and 66.76 ± 5.35% of the female rats. Evidently the assumption held by current researchers regarding stepping force measurement is not realistic in terms of application, and as this study has shown, the use of a video display frame is essential for the identification of the front and hind paws through the peak signals.

Anti-hyperglycaemic activity of swietenia macrophylla king (meliaceae) seed extracts in normoglycaemic rats undergoing glucose tolerance tests.

BACKGROUND: Swietenia macrophylla King (Meliaceae) is used to treat diabetes mellitus in Malaysia. This study aims to evaluate the anti-hyperglycaemic potential of petroleum ether (PE), chloroform (CE) and methanol (ME) extracts of S. macrophylla seeds, in normoglycaemic and streptozotocin (STZ)-induced diabetic rats. METHODS: Following treatment of normoglycaemic rats with S. macrophylla seed extracts, hypoglycaemic and intraperitoneal glucose tolerance tests (IPGTT) were performed, and blood glucose concentrations were measured. Similarly, glucose concentrations were measured after 1 and 14 days of extract treatment of STZ-induced diabetic rats. Glucose absorption by isolated everted intestine and glucose uptake by isolated abdominal muscle were tested after treatment with seed extracts. Gas chromatography mass spectrometry (GC-MS) analysis was performed on PE of S. macrophylla seeds to identify the compounds responsible for its activity. RESULTS: None of the extracts had a significant effect on the blood glucose levels of 60 randomly selected normoglycaemic (normal) and diabetic rats undergoing hypoglycaemic tests. PE, however, significantly reduced blood glucose levels in 30 randomly selected normoglycaemic rats undergoing IPGTT tests 30-120 minutes after glucose administration. Repeated doses of 1000 mg/kg and 500 mg/kg PE to STZ-induced diabetic rats for 14 days did not reduce blood glucose levels significantly. PE did not significantly reduced the intestinal absorption of glucose, but significantly increased glucose uptake by abdominal muscle in the absence or presence of insulin. GC-MS analysis indicated that diterpenes, triterpenoids, fatty acid methyl esters, aldehydes and phytosterols may be responsible for the glucose lowering effects of PE. CONCLUSION: PE extracts of S. macrophylla seeds showed anti-hyperglycaemic activity on IPGTTs . GC-MS analysis on the PE revealed that several compounds, including fucosterol and ß-sitosterol, may be responsible for these anti-hyperglycaemic properties.

Safety assessment of standardised methanol extract of Cinnamomum burmannii.

The present study aims to evaluate the safety of methanol extract of Cinnamomum burmannii (MECB) by acute 14-day (single dose) and sub-chronic 28-day (repeated doses) oral administration to Sprague-Dawley rats. Our results showed that no toxicity was found in either acute or sub-chronic toxicity studies. MECB (containing 0.07% and 0.20% (w/w) of coumarin and trans-cinnamaldehyde, respectively), which was given orally at doses of 500, 1000 and 2000 mg/kg caused neither visible signs of toxicity nor mortality. No significant differences were observed in general condition, growth, organ weight, hematological parameters, biochemical values, or the gross and microscopic appearance of the organs from the treatment groups as compared to the control group. In conclusion, MECB did not cause any mortality nor did it cause any abnormalities in the necropsy and histopathology findings of treated rats. The LD50 for the MECB was found to be more than 2000 mg/kg. No adverse effects were observed in the treated rats at all the doses tested. The no-observed-adverse-effect level (NOAEL) for the 28-day study was determined to be 2000 mg/kg body weight/day.