Toxicological assessment of Opuntia dillenii (Ker Gawl.) Haw. cladode methanol extract, fractions and its alpha pyrones: Opuntiol and opuntioside.

ETHNOPHARMACOLOGICAL RELEVANCE: The edible plant Opuntia dillenii (Ker Gawl.) Haw. commonly known as Nagphana, belongs to the Cactaceae family. It is traditionally used to treat various ailments including inflammation, gastric ulcers, diabetes, hepatitis, asthma, whooping cough and intestinal spasm. AIM OF THE STUDY: Despite its traditional use in various countries, detailed toxicological studies of O. dillenii cladode are few. Thus in the current study, toxicity of O. dillenii cladode derived methanol extract, fractions and its α-pyrones: opuntiol and opuntioside have been addressed. METHODS: The test agents were assessed using both in vitro and in vivo toxicity assays. MTT on human embryonic kidney cell line (HEK-293), tryphan blue exclusion in rat neutrophils, Cytokinesis-B block micronucleus (CBMN) in human lymphocytes and genomic DNA fragmentation using agarose gel electrophoresis were performed. In acute toxicity test, mice orally received extract (5 g/kg) for 7 days followed by measurements of relative organ weight, biochemical (blood profile, liver and kidney function test) and histological studies (liver and kidney) were carried out. Rat bone marrow micronucleus genotoxicity assay was also conducted. RESULTS: O. dillenii derived test agents were non-cytotoxic and had no effect on the integrity of DNA. Methanol extract (5 g/kg) orally administered in mice did not cause any significant change in relative organ weights, biochemical parameters and liver and kidney histology as compared to vehicle control. In parallel, extract did not stimulate micronuclei formation in rat bone marrow polychromatic erythrocytes. CONCLUSION: These results led to conclude that edible O. dillenii extract is non-toxic via the oral route and appears to be non-cyto-, hepato-, nephro- or genotoxic, thereby supporting its safe traditional use against various ailments. Therefore, opuntiol and opuntioside may serve as lead compounds in designing new drug(s) derived from edible plants.

Effects of 1,2,4,6-tetra-O-galloyl-ß-D-glucose from P. emblica on HBsAg and HBeAg secretion in HepG2.2.15 cell culture.

A polyphenolic compound, 1,2,4,6-tetra-O-galloyl-ß-D-glucose (1246TGG), was isolated from the traditional Chinese medicine Phyllanthus emblica L. (Euphorbiaceae) and assayed for its potential as an anti-hepatitis B virus (HBV) agent. The cytotoxicity of 1246TGG on HepG2.2.15 as well as HepG2 cells was determined by observing cytopathic effects, and the effects of 1246TGG on secretion of HBsAg and HBeAg in HepG2.2.15 cells were assayed by enzyme immunoassay. Results indicates that treatment with 1246TGG (6.25 µg/mL, 3.13 µg/mL), reduced both HBsAg and HBeAg levels in culture supernatant, yet the inhibitory effects tend to decline with the assay time. This study provides a basis for further investigation of the anti-HBV activity and possible mechanism of action of 1246TGG.

Identification of C-glycoside flavonoids as potential mutagenic compounds in kava.

Kava (Piper methysticum) extract products have been implicated in a number of severe hepatotoxicity cases. However, systematic toxicological studies regarding kava consumption have not been reported. In this study, 6 major kavalactones and different solvent fractions of kava roots, leaves, and stem peelings were evaluated for their mutagenic potential. None of the kavalactones was found to be positive in the experimental concentration ranges tested by the umu test (a sensitive test for point mutations). However, among the different solvent fractions, the n-butanol fraction of kava leaves was positive. Further investigations using bioassay-directed isolation and analysis indicated that 2 C-glycoside flavonoid compounds accounted for the positive mutagenic results. Two isolated compounds were identified as 2''-O-rhamnosylvitexin and schaftoside by NMR and MS techniques.

Antihyperglycemic activity of kinsenoside, a high yielding constituent from Anoectochilus roxburghii in streptozotocin diabetic rats.

Different doses of kinsenoside, a high yielding constituent from Anoectochilus roxburghii, was orally administered to further investigate its biological activity and pharmacological mechanisms that involve in the hypoglycemic effect on streptozotocin (STZ) diabetic rats. Our study showed that this compound exhibited significantly antihyperglycemic activity at the dose of 15mg/kg body weight, which is speculated to be partially attributed to modulating the activity of enzymatic antioxidants, scavenging free radicals, and reducing the content of factor NO. Much more intact beta cells in the islets of Langerhans with denser insulin in kinsenoside-treated groups than the negative control were observed, which greatly supported the morphological and functional elucidation. These results displayed that kinsenoside could be useful for repairing beta cells in pancreatic islet injury as well as improving its function. The OGTT evidenced that this compound could promote the glucose tolerance of acute glucose increase in both diabetic and normal healthy rats.

Bioassay-guided isolation of kaempferol-3-O-beta-D-galactoside with anti-inflammatory and antinociceptive activity from the aerial part of Calluna vulgaris L.

Calluna vulgaris L. (Ericaceae) is used for the treatment of various inflammatory ailments in traditional medicines. In order to evaluate this ethnobotanical information, its anti-inflammatory and antinociceptive activities were studied using in vivo experimental models in mice. The ethanolic extract of the plant was first fractionated into five extracts; namely, n-hexane, chloroform, ethyl acetate (EtOAc), n-butanol, and water fractions. Among them, the EtOAc Fr. was found to be the most effective and was further subjected to bioassay-guided fractionation and isolation procedures. After successive column chromatography applications, on Sephadex LH-20 and silica gel, a component, which is responsible for the above-mentioned activities of this species of Turkish origin, was isolated and its structure was elucidated as kaempferol-3-O-beta-D-galactoside, a common flavonol derivative by means of spectral techniques.

Hypotensive activity, toxicology and histopathology of opuntioside-I and methanolic extract of Opuntia dillenii.

Methanolic extract of Opuntia dillenii cladodes and its pure compound alpha-pyrone glycoside, opuntioside-I showed potent hypotensive activity in normotensive rats. Both the extract and opuntioside-I showed comparable effect of 44-54% fall in Mean Arterial Blood Pressure (MABP) at the dose of 10 mg/kg. No mortality was observed in rats even at the doses of 1000 mg/kg/d and 900 mg/kg/d per oral of extract and opuntioside-I respectively. However, histopathology revealed adverse effects of high doses on liver and spleen of the experimental animals.

Sulfonated xanthones from Hypericum sampsonii.

Xanthones, 1,3-dihydroxy-5-methoxyxanthone-4-sulfonate and 1,3-dihydroxy-5-O-beta-D-glycopyranosylxanthone-4-sulfonate, together with nine known compounds were obtained from H. sampsonii. This is the first report of sulfonated xanthonoids. Furthermore, compounds 1 and 2 exhibited significant cytotoxicity against the P388 cancer cell line.