GC/Mass analysis of the volatile compounds of P. hyrcanicum diethyl ether extract and GC profiling of some Iranian Polygonum species

In this study, the relationship among four species of Polygonum (including P. hyrcanicum (three samples), P. persicaria, P. avicular, and P. hydropiper) was investigated by GC profiling. Furthermore, the major compounds of the ethylic ether extract of P. hyrcanicum were identified by GC/MS as: α-bisabolol (17.5%), cedrol (15.9%), sesquisabinene hydrate (13.0%), α-elemol (10.5%) and trans-longipinocarveol (10.1%). All the identified compounds were sesquiterpenes and no monoterpene, fatty acid and/or hydrocarbone were detected in the extract. Chemical distances among the mentioned species were calculated in order to construct the dendrogram of closely related samples. Results indicated that the distance between two samples of P. hyrcanicum was considered to be short and their GC profiles were quite similar to each other and also there was a close relationship between the two samples of Polygonum with P. avicular. P. hydropiper was observed far from the two samples of P. hyrcanicum in comparison to other samples. Interestingly, P. hyrcanicum, gathered from Veresk, had no close relationship with other pairs of P. hyrcanicum.The results of this study support the phylogenetic relationships among these Polygonum species which was previously reported

Validation of UHPLC-MS/MS methods for the determination of kaempferol and its metabolite 4-hydroxyphenyl acetic acid, and application to in vitro BBB and intestinal drug permeability studies

Sedative and anxiolytic-like properties of flavonoids such as kaempferol and quercetin, and of some of their intestinal metabolites, have been demonstrated in pharmacological studies. However, routes of administration were shown to be critical for observing in vivo activity. Therefore, the ability to cross intestinal and blood-brain barriers was assessed in cell-based models for kaempferol (KMF), and for the major intestinal metabolite of KMF, 4-hydroxyphenylacetic acid (4-HPAA). Intestinal transport studies were performed with Caco-2 cells, and blood-brain barrier transport studies with an immortalized monoculture human model and a primary triple-co-culture rat model. UHPLC–MS/MS methods for KMF and 4-HPAA in Ringer-HEPES buffer and in Hank’s balanced salt solution were validated according to industry guidelines. For all methods, calibration curves were fitted by least-squares quadratic regression with 1/X2 as weighing factor, and mean coefficients of determination (R2) were >0.99. Data obtained with all barrier models showed high intestinal and blood-brain barrier permeation of KMF, and no permeability of 4-HPAA, when compared to barrier integrity markers

Caco-2 permeability studies and hERG liability assessment of tryptanthrin and indolinone

Tryptanthrin and (E,Z)-3-(4-hydroxy-3,5-dimethoxybenzylidene)indolinone (indolinone) were recently isolated from Isatis tinctoria as potent anti-inflammatory and antiallergic alkaloids, and shown to inhibit COX-2, 5-LOX catalyzed leukotriene synthesis, and mast cell degranulation at low µM to nM concentrations. To assess their suitability for oral administration, we screened the compounds in an in vitro intestinal permeability assay using human colonic adenocarcinoma cells. For exact quantification of the compounds, validated UPLC-MS/MS methods were used. Tryptanthrin displayed high permeability (apparent permeability coefficient > 32.0 × 10(-6) cm/s) across the cell monolayer. The efflux ratio below 2 ( 10 µM) and indolinone (IC50 of 24.96 µM). The analysis of compounds using various in silico methods confirmed favorable pharmacokinetic properties, as well as a slight inhibition of the human ether-a-go-go-related gene potassium channel at micromolar concentrations