Pharmacokinetics of calycopterin and xanthmicrol, two polymethoxylated hydroxyflavones with anti-angiogenic activities from Dracocephalum kotschyi Bioss.

BACKGROUND: Recently flavonoids have attracted the attention of researchers in the fight against cancer. Calycopterin and xanthomicrol, are two polymethoxylated flavonoids found in the aerial parts of Dracocephalum kotschyi Bioss.. We have recently shown that these compounds possess antiangiogenic activity and may be of value as potential anticancer agents. In order to demonstrate putative in vivo antitumor effect of these compounds we needed preliminary information on both pharmacokinetics and toxicological properties of these two agents. METHOD: A new online SPE HPLC method for measurement of calycopterin and xanthomicrol in rat plasma was developed. Pharmacokinetic parameters of calycopterin and xanthomicrol, after i.v. administration in rats, were determined. RESULTS: The plasma half-life for both agents was around 4 h, however, the volume of distribution of calycopterin appeared to be about 8 times greater than xanthomicrol. This was probably due the greater hydrophobicity of the former which had other consequences such as much smaller maximum plasma concentration of calycopterin compared to its less methoxylated congener. Preliminary toxicological study of xanthomicrol failed to show any behavioral, histological and biochemical adverse effects after repeated administrations of high doses. Pharmacokinetics of xanthomicrol in rats.

Evaluation of DNA damage of hydro-alcoholic and aqueous extract of Echium amoenum and Nardostachys jatamansi.

BACKGROUND: Today most of herbal medicines are marketing without any standard safety profiles. Although common assumption is that these products are nontoxic but this assumption may be incorrect and dangerous, so toxicological studies should be done for herbal drugs. According to the frequent use of Echium amoenum as immunostimulant and useful in conditions including pain, cough, sore throat and arthritis, and Nardostachys jatamansi as tranquilizer and sleep inducer and evidences of some toxicities, we assessed the probable effect of their extracts on DNA of hepG2 cells using the comet assay. MATERIALS AND METHODS: Different concentrations of above extracts of the plants are incubated with hepG2 cells for 24 h. A mixture of cell suspension and agarose gel were put on slides, then slides were embedded in a lysing solution and were put in electrophoresis buffer (pH = 13). Then the electrophoresis procedure took place in an alkaline solution and after neutralization stage, colorization was done by ethidium bromide and comets were observed using a fluorescence microscope. At least 100 cells of each sample were evaluated and three parameters including comet length, percent of DNA in tail, and tail moment were assessed. RESULTS: Both Aqueous and hydro-alcoholic extract of E. amoenum were genotoxic in the concentrations of 25 mg/ml and aqueous and hydro-alcoholic extract of N. jatamansi were genotoxic in the concentrations 5 and 10 mg/ml, respectively. CONCLUSIONS: Although E. amoenum and N. jatamansi are highly used in medicine, these herbs have genotoxic effects in determined concentrations and they should be used cautiously.