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.

Evaluation of anti-cancer activity of Acanthester planci extracts obtained by different methods of extraction.

Acanthaster planci, the crown-of-thorns starfish, naturally endowed with the numerous toxic spines around the dorsal area of its body. Scientific investigations demonstrated several toxico-pharmacological efficacies of A. planci such as, myonecrotic activity, hemorrhagic activity, hemolytic activity, mouse lethality, phospholipase A2 (PLA2) activity, capillary permeability-increasing activity, edema-forming activity, anticoagulant activity and histamine-releasing activity from mast cells. The present study was performed to evaluate the cytotoxic activity of A. planci extracts obtained by different methods of extraction on MCF-7 and HCT-116, human breast and colon cancer cell lines, respectively. Results of the cell proliferation assay showed that PBS extract exhibited very potent cytotoxic activity against both MCF-7 and HCT-116 cell lines with IC(50) of 13.48 µg/mL and 28.78 µg/mL, respectively, while the extracts prepared by Bligh and Dyer method showed moderate cytotoxicity effect against MCF-7 and HCT-116 cell lines, for chloroform extract, IC(50) = 121.37 µg/mL (MCF-7) and 77.65 µg/mL (HCT-116), and for methanol extract, IC(50) = 46.11 µg/mL (MCF-7) and 59.29 µg/mL (HCT-116). However, the extracts prepared by sequential extraction procedure from dried starfish found to be ineffective. This study paves the way for further investigation on the peptide composition in the PBS extract of the starfish to discover potential chemotherapeutic agents.

Cytostatic and Antiproliferative Activities of F5 Fraction of Crinum amabile Leaf Chloroform Extract Showed Its Potential as Cancer Chemotherapeutic Agent.

Medicinal plants have been considered as promising sources of drugs in treating various cancers. Crinum amabile (C. amabile), a plant species from the Amaryllidaceae family, is claimed to be a potential source for cancer chemotherapeutic compounds. Here, we aimed to investigate the potential of C. amabile as an anticancer agent. Dried leaves of C. amabile were serially extracted and our findings showed that chloroform extract (CE) was shown to exhibit cytotoxic effect against all cancer cell lines used. This active extract was further fractionated in which F5 fraction was shown to possess the highest cytotoxicity among all fractions. F5 fraction was then tested in-depth through Annexin V/FITC apoptosis and DNA fragmentation assays to determine its apoptotic effect on MCF-7 cells. Results revealed that F5 fraction only showed induction of cell apoptosis starting at 72-hour treatment while DNA fragmentation was not detected at any of the concentrations and treatment periods tested. Meanwhile, cell proliferation assay revealed that F5 fraction was able to inhibit normal cell proliferation as well as VEGF-induced cell proliferation of normal endothelial cell (HUVECs). In conclusion, F5 fraction from C. amabile leaf CE was able to exhibit cytostatic effect through antiproliferation activity rather than induction of cell apoptosis and therefore has the potential to be further investigated as an anticancer agent.

Antioxidant and toxicity studies of 50% methanolic extract of Orthosiphon stamineus Benth.

The present study evaluated the antioxidant activity and potential toxicity of 50% methanolic extract of Orthosiphon stamineus (Lamiaceae) leaves (MEOS) after acute and subchronic administration in rats. Superoxide radical scavenging, hydroxyl radical scavenging, and ferrous ion chelating methods were used to evaluate the antioxidant properties of the extract. In acute toxicity study, single dose of MEOS, 5000 mg/kg, was administered to rats by oral gavage, and the treated rats were monitored for 14 days. While in the subchronic toxicity study, MEOS was administered orally, at doses of 1250, 2500, and 5000 mg/kg/day for 28 days. From the results, MEOS showed good superoxide radical scavenging, hydroxyl radical scavenging, ferrous ion chelating, and antilipid peroxidation activities. There was no mortality detected or any signs of toxicity in acute and subchronic toxicity studies. Furthermore, there was no significant difference in bodyweight, relative organ weight, and haematological and biochemical parameters between both male and female treated rats in any doses tested. No abnormality of internal organs was observed between treatment and control groups. The oral lethal dose determined was more than 5000 mg/kg and the no-observed-adverse-effect level (NOAEL) of MEOS for both male and female rats is considered to be 5000 mg/kg per day.

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.

Toxicity evaluation of a standardised 50% ethanol extract of Orthosiphon stamineus.

AIM OF THE STUDY: The present investigation was carried out to evaluate the safety of standardised 50% ethanol extract of Orthosiphon stamineus plant by determining its potential toxicity after acute and subchronic administration in rats. MATERIALS AND METHODS: For acute toxicity study, up and down method (limit dose) was adapted. A single dose of 5000 mg/kg of the standardised 50% ethanol extract of O. stamineus was given orally to 5 healthy Sprague-Dawley (SD) female adult rats. The rats were observed for mortality and clinical signs for 3 h and then periodically for 14 days. While in the subchronic toxicity study, the extract was administered orally at doses of 1250, 2500 and 5000 mg/kg per day for 28 days to female and male SD rats, respectively. The animals were sacrificed, followed by examination of their organs and blood serum. RESULTS: In the acute toxicity study, standardised 50% ethanol extract of O. stamineus at a dose of 5000 mg/kg caused neither visible signs of toxicity nor mortality. All five rats survived until the end of observation period. While in subchronic toxicity, administration of the standardised 50% ethanol extract of O. stamineus at 1250, 2500, and 5000 mg/kg for 28 days did not produce any mortality and there were no significant differences in the general condition, growth, organ weights, hematological parameters, clinical chemistry values, or gross and microscopic appearance of the organs from the treatment groups as compared to the control group. CONCLUSIONS: Standardised 50% ethanol extract of O. stamineus did not cause any death nor did it cause abnormalities in necropsy and histopathology findings. There were no acute or subchronic toxicity observed and this extract could be devoid of any toxic risk. The NOAEL for the standardised 50% ethanol extract of O. stamineus is 5000 mg/kg per day for 28 days.

Acute and subchronic oral toxicity of Coriolus versicolor standardized water extract in Sprague-Dawley rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Coriolus versicolor, which is known as Yun Zhi, is one of the commonly used Chinese medicinal herbs. Recent studies have demonstrated its antitumor activities on cancer cells which led to its widespread use in cancer patient. However, little toxicological information is available regarding its safety. The present study evaluated the potential toxicity of Coriolus versicolor standardized water extract after acute and subchronic administration in rats. MATERIALS AND METHODS: In acute toxicity study, Coriolus versicolor water extract was administered by oral gavage to Sprague-Dawley (SD) rats (6 males, 6 females) at single doses of varying concentrations 1250, 2500 and 5000 mg/kg. In subchronic toxicity study, the extract was administered orally at doses of 1250, 2500 and 5000 mg/kg/day for 28 days to male and female SD rats respectively. General behavior, adverse effects and mortality were determined throughout the experimental period. Haematological and biochemical parameters, relative organ weights and histopathological were evaluated at the end of the experiment. RESULTS: There were no mortality and signs of toxicity in acute and subchronic toxicity studies. In the single dose acute toxicity and repeated dose 28-day subchronic toxicity studies, there were no significant difference in body weight, relative organ weight, haematological parameters, clinical chemistry, gross pathology and histopathology between treatment and control groups. CONCLUSIONS: Coriolus versicolor water extract did not cause remarkable adverse effect in SD rats. The oral lethal dose of Coriolus versicolor water extract is more than 5000 mg/kg and no-observed-adverse-effect level (NOAEL) of the extract for both male and female rats is 5000 mg/kg per day for 28 days.

Antioxidant and hepatoprotective effects of Murdannia bracteata methanol extract.

Murdannia bracteata (C. B. Clarke) is a local plant that is widely used in Malaysia as a traditional remedy for various diseases of the kidney and liver, including inflammation and cancer. In the present study, we investigated the antioxidant and hepatoprotective activities of M. bracteata methanol extract (MB). 2,2'-diphenyl-1-picrylhydrazyl radical scavenging activity, lipid peroxidation inhibition and trolox equivalent antioxidant capacity of MB were determined. The hepatoprotective activity of MB was studied using a CCl(4)-induced liver toxicity model in rats. The hepatoprotective effect was assessed by monitoring the plasma malondialdehyde level and serum alanine transaminase and aspartate transaminase activities. Histopathological changes of hepatic tissue were also investigated. The results indicated that MB possessed potential antioxidant, lipid peroxidation inhibition and free radical scavenging activities. Pretreatment of rats with MB (500 mg/kg and 1000 mg/kg per os) before induction of CCl(4)-induced hepatotoxicity showed a dose-dependent reduction in the necrotic changes in hepatic tissue. The increases in plasma malondialdehyde level, serum alanine transaminase and aspartate transaminase activities were also significantly inhibited by MB. The total phenolic content of MB determined using Folin-Ciocalteu assay was found to be 10%. The results of the present study indicated that the hepatoprotective effect of MB is most likely due to its antioxidant and free radical scavenging properties.