Modulation of P-glycoprotein activity by acridones and coumarins from Citrus sinensis

Bioguided fractionation of the roots of Citrus sinensis (Rutaceae) led to the isolation and identification of five coumarins, namely, clausarin, suberosin, poncitrin, xanthyletin and thamnosmonin, seven acridones, namely, acrimarine B, 2-methoxycitpressine I, citpressine I, buntanine, acrimarine E, honyumine and acrimarine C, and one terpenoid, namely, limonin. Among these compounds, clausarin, 2-methoxycitpressine I and acrimarine E inhibited P-glycoprotein-mediated drug efflux in K562/R7 human leukemic cells over-expressing P-glycoprotein

Sesquiterpenes from aerial parts of Ferula vesceritensis

From the dichloromethane extract of aerial parts of Ferula vesceritensis (Apiaceae), 11 sesquiterpene derivatives were isolated. Among them five were compounds designated as 10-hydroxylancerodiol-6-anisate, 2,10-diacetyl-8-hydroxyferutriol-6-anisate, 10-hydroxylancerodiol-6-benzoate, vesceritenone and epoxy-vesceritenol. The six known compounds were identified as feselol, farnesiferol A, lapidol, 2-acetyl-jaeschkeanadiol-6-anisate, lasidiol-10-anisate and 10-oxo-jaesckeanadiol-6-anisate. All the structures were determined by extensive spectroscopic studies including 1D and 2D NMR experiments and mass spectroscopy analysis. Two of the compounds, the sesquiterpene coumarins farnesiferol A and feselol, bound to the model recombinant nucleotide-binding site of an MDR-like efflux pump from the enteropathogenic protozoan Cryptosporidium parvum

Selective modulation of P-glycoprotein activity by steroidal saponines from Paris polyphylla

Bio-guided fractionation of the roots of Paris polyphylla (Trilliaceae), based on inhibition of P-glycoprotein-mediated daunorubicin efflux in K562/R7 cell line, led to isolation and identification of the three saponins 3-O-Rha(1 → 2)[Ara(1 → 4)]Glc-pennogenine, gracillin and polyphyllin D, and the two ecdysteroids 20-hydroxyecdysone and pinnatasterone. These compounds were tested for multidrug reversion on P-glycoprotein (ABCB1) with both drug-selected and transfected cell lines, and also on Breast Cancer Resistance Protein (BCRP/ABCG2). By contrast to a weak efficiency on BCRP, the three saponins displayed significant effects as inhibitors of P-glycoprotein-mediated drug efflux

Isoflavones from Ficus nymphaeifolia

A new isoflavone, 5,7-dihydroxy-4\u27-methoxy-3\u27-(2,3-dihydroxy-3-methylbutyl)isoflavone was isolated from the stem bark of Ficus nymphaefolia Mill. (Moraceae) together with eight known isoflavones: genistein, erycibenin A, cajanin, 5,7,2\u27-trihydroxy-4\u27-methoxyisoflavone, erythrinin C, alpinumisoflavone, derrone and 3\u27-(3-methylbut-2-enyl)biochanin A. Their structures were established by spectral analysis including 1D and 2D NMR experiments

Isoflavones from ficus nymphaefolia

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Modulation of cancer cell multidrug resistance by an extract of Ficus citrifolia.

International audienceMultidrug resistance due to P-glycoprotein is a serious impediment to successful chemotherapy of cancer. Previous studies have shown that natural compounds such as prenyl flavonoids are able to modulate the multidrug resistance phenotype of P-glycoprotein-positive cancer cells. A fraction from the dichloromethane extract of a common Guadalupe Ficus, Ficus citrifolia was studied for its direct interaction with the purified C-terminal cytosolic domain of P-glycoprotein, and for its induced accumulation and cytotoxicity of vinblastine and daunomycin in two model cell lines overexpressing P-glycoprotein, namely K562/R7 and MESSA/Dx5. The fraction bound with high affinity to P-glycoprotein C-terminal cytosolic domain and was as efficient as cyclosporin A to increase intracellular accumulation of daunomycin in K562/R7 leukemic cells. Moreover, the fraction markedly enhanced the cytotoxic effect of vinblastine on the growth of MESSA/Dx5 cells. These results suggest that Ficus citrifolia possesses important therapeutic potential for improving the efficacy of cancer chemotherapy.Multidrug resistance due to P-glycoprotein is a serious impediment to successful chemotherapy of cancer. Previous studies have shown that natural compounds such as prenyl flavonoids are able to modulate the multidrug resistance phenotype of P-glycoprotein-positive cancer cells. A fraction from the dichloromethane extract of a common Guadalupe Ficus, Ficus citrifolia was studied for its direct interaction with the purified C-terminal cytosolic domain of P-glycoprotein, and for its induced accumulation and cytotoxicity of vinblastine and daunomycin in two model cell lines overexpressing P-glycoprotein, namely K562/R7 and MESSA/Dx5. The fraction bound with high affinity to P-glycoprotein C-terminal cytosolic domain and was as efficient as cyclosporin A to increase intracellular accumulation of daunomycin in K562/R7 leukemic cells. Moreover, the fraction markedly enhanced the cytotoxic effect of vinblastine on the growth of MESSA/Dx5 cells. These results suggest that Ficus citrifolia possesses important therapeutic potential for improving the efficacy of cancer chemotherapy