Toxic potentials of ten herbs commonly used for aphrodisiac effect in Turkey.

BACKGROUND/AIM: Sexual dysfunction is a serious problem worldwide. In Turkey, herbal products are used by some people suffering from sexual dysfunction. Despite their therapeutic advantages, some constituents of herbs are potentially toxic and pose health risks because they can be bought from the market without a prescription. Therefore, we aimed to determine the safety of herbs possessing aphrodisiac effects, chosen on the basis of their frequency of medicinal use and commercial importance in Turkey. MATERIALS AND METHODS: Ten herbs (Anethum graveolens, Carthamus tinctorius, Citrus aurantium, Cocos nucifera, Glycyrrhiza glabra, Melissa officinalis, Nigella arvensis, Pinus pinea, Prunus mahaleb, and Zingiber officinale) were extracted with water, methanol, and chloroform. The cyto- and genotoxic potentials of the extracts were assessed using an MTT test on a rat kidney cell line and an Ames assay in Salmonella typhimurium strains, respectively. RESULTS: In the cytotoxic evaluation, IC50 values were 1.51-31.4 mg/mL for the methanol and chloroform extracts, while the water extracts were not cytotoxic. In the genotoxic evaluation, it was revealed that the water extracts had more mutagenic activity than the chloroform and methanol extracts. Water extract of M. officinalis was shown to have the most genotoxic activities to TA100 (±S9) and TA98 (-S9). CONCLUSION: These results might be useful in determining the toxic effects of herbs and lead to precautions being taken in regards to their consumption.

Current regulatory perspectives on genotoxicity testing for botanical drug product development in the U.S.A.

Genotoxicity testing is an important part of preclinical safety assessment of new drugs and is required prior to Phase I/II clinical trials. It is designed to detect genetic damage such as gene mutations and chromosomal aberration, which may be reflected in tumorigenic or heritable mutation potential of the drug. Botanical new drugs in the U.S. are entitled to a waiver for preclinical pharmacology/toxicology studies, including genotoxicity testing, in support of an initial clinical trial under IND, contingent on previous human experience. Recently, ethical concerns have been raised over conducting Phase I/II clinical trials of new drugs with positive genotoxicity findings in healthy volunteers. Although the relevance of this issue to patients, as opposed to healthy volunteers, depends on the drug's indication, duration of treatment, and specific findings related to the assays, the regulatory view is to avoid exposing patients to genotoxic compounds unnecessarily in clinical trials. This philosophy may impact on herbal supplement marketing and botanical drug development, in that genotoxicity data are often lacking while consumers are exposed to the herbal supplement, or healthy volunteers are tested in an initial Phase I/II clinical trial on the botanical drug. This paper presents results of a survey conducted on genotoxicity data in botanical INDs submitted to the Agency and discusses the significance of this information. The information presented indicates that the sponsors of botanical INDs have increasingly recognized the importance of genotoxicity information and may have prioritized its acquisition in their strategic drug development programs.

Fisher information matrix of the Dirichlet-multinomial distribution.

In this paper we derive explicit expressions for the elements of the exact Fisher information matrix of the Dirichlet-multinomial distribution. We show that exact calculation is based on the beta-binomial probability function rather than that of the Dirichlet-multinomial and this makes the exact calculation quite easy. The exact results are expected to be useful for the calculation of standard errors of the maximum likelihood estimates of the beta-binomial parameters and those of the Dirichlet-multinomial parameters for data that arise in practice in toxicology and other similar fields. Standard errors of the maximum likelihood estimates of the beta-binomial parameters and those of the Dirichlet-multinomial parameters, based on the exact and the asymptotic Fisher information matrix based on the Dirichlet distribution, are obtained for a set of data from Haseman and Soares (1976), a dataset from Mosimann (1962) and a more recent dataset from Chen, Kodell, Howe and Gaylor (1991). There is substantial difference between the standard errors of the estimates based on the exact Fisher information matrix and those based on the asymptotic Fisher information matrix.

Evaluation of gamma-hydroxybutyric acid for genotoxicity in the mouse micronucleus assay.

Gamma-hydroxybutyric acid (GHB) is an endogenous compound found in the brain and other tissues of mammals. Neurotransmitter/neuromodulator functions have been ascribed to GHB, which has lately become a drug of abuse. In this study, we tested GHB for genotoxicity by measuring its ability to induce micronuclei in polychromatic erythrocytes (reticulocytes) in the peripheral blood of mice. Intraperitoneal injection with a dose of 25 mg/kg/day for 3 days or 50 mg/kg/day x 3 days resulted in a significant (by Dunnett's test) increase of 1.9- to 2.1-fold in micronuclei. However, because increases were small and because no consistent dose-dependent increase in induced micronuclear frequency could be demonstrated, our results do not conclusively show that GHB is an in vivo genotoxicant in mammals.

[A toxicological study of a phytopreparation made from an extract of alfalfa (Medicago sativa)]. / Toksikologicheskoe izuchenie fitopreparata iz ékstrakta liutserny posevnoi.

A phytopreparation from lucerne (Medicago sativa) was studied with respect to the acute and chronic toxicity and the action upon the cellular genetic mechanism. It was found that the preparation belongs to the group of practically nontoxic properties.

[The antimutagenic activity of biomass extracts from the cultured cells of medicinal plants in the Ames test]. / Doslizhzhennia antymutahennoï aktyvnosti ekstraktiv iz biomasy kul'tyvovanykh klityn deiakykh likars'kykh roslyn u testi Eimsa.

Antimutagenic activity of 20 and 40% ethanol extracts from the biomass of Rhodiola rosea, Polyscias filicifolia, Panax ginseng and Ungernia victoris cultured cells have been studied. DDDTDP, ethidium bromide, benz(a)pyrene, benzidine served as model mutagens for Salmonella typhimurium TA 98 strain (the latter two were tested in presence of metabolic activation system); for S. typhimurium TA 100 strain these were tio-tefa, bichromate potassium and sodium azide and heavy metal compounds (chlorides of manganese, zinc, cadmium, lead acetate) for both strains. Higher capacity of the extracts from the biomass of R. rosea and P. filicifolia to counteract gene mutations induced by various mutagens was demonstrated (ca. 90% inhibition in isolated cases). In the experiment with the metabolic activation most effective proved to be the extracts from the P. ginseng biomass (up to 34% and 47% mutagenicity inhibition).