Phytochemical analysis and biological activity testing of novel geranyl flavonoids from Paulownia tomentosa fruits

Kód výsledku v IS VaVaI

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Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Phytochemical analysis and biological activity testing of novel geranyl flavonoids from Paulownia tomentosa fruits

Popis výsledku v původním jazyce

Flavonoids represent a wide group of biologically active compounds isolated from Paulownia tomentosa (Thunb.) Siebold et Zucc. ex Steud. (Paulowniaceae). Their antiphlogistic, anti- and pro-oxidant properties have been already observed in vitro and in vivo. Moreover, flavonoids with geranyl side chain, so-called geranylated flavonoids, are known also for their strong cytotoxic potential. Three novel C-geranylated flavonoids, together with two previously described geranyl flavonoids, tomentodiplacone and 3 ?-O-methyl-5 ?-hydroxydiplacone, have been isolated from chloroform part of ethanol extract of P. tomentosa fruits. Several chromatographic methods, including classic column chromatography, TLC, analytical and preparative HPLC were applied in the separation and isolation process. The structures of isolated compounds were determined using different spectral methods (UV, IR, MS and NMR). The cytotoxic effect was assessed in vitro on the model of THP-1 human leukemic monocytes using WST-1 and LDH assay. A newly isolated flavone with unsubstituted C-geranyl side chain has shown a potent cytotoxic effect with IC50 4.5 ? 1.2 ?M. The cytotoxic activity of flavanones with cyclized C-geranyl moiety was lower. Furthermore, the non-toxic concentrations of compounds were used for evaluation of anti/pro-oxidant and anti-inflammatory properties. The antioxidant activity against the generation of reactive oxygen species in pyocyanin-stimulated monocytes has been assessed by measurement of fluorescent 2 ?,7 ?-dichlorofluorescein (DCF) product. Whereas the geranyl side chain and its substitution play a substantial role in the cytotoxic action of flavonoids, these two aspects have only a small impact on their antioxidant properties. Positional arrangement of substituents on the flavonoid skeleton seems to be more important. Our investigation of antioxidant properties has confirmed this thesis. Moreover, the ability to attenuate the activation of transcriptional factors NF?B/AP-1 implicated in inflammatory processes has been evaluated on the model of THP1-XBlueTM-MD2-CD14 cells. Lipopolysaccharide (LPS) stimulation of TLR4 receptors in this cell line induced signaling cascades leading to the activation of NF-?B and AP-1 and the subsequent production of SEAP reporter protein was measured. Two novel flavanones have shown the capability to decrease the activity of NF?B/AP-1 in statistically significant manner. The phytochemical analysis and biological activity testing of novel geranyl flavonoids have extended the existent knowledge about constituents isolated from P. tomentosa species

Název v anglickém jazyce

Phytochemical analysis and biological activity testing of novel geranyl flavonoids from Paulownia tomentosa fruits

Popis výsledku anglicky

Flavonoids represent a wide group of biologically active compounds isolated from Paulownia tomentosa (Thunb.) Siebold et Zucc. ex Steud. (Paulowniaceae). Their antiphlogistic, anti- and pro-oxidant properties have been already observed in vitro and in vivo. Moreover, flavonoids with geranyl side chain, so-called geranylated flavonoids, are known also for their strong cytotoxic potential. Three novel C-geranylated flavonoids, together with two previously described geranyl flavonoids, tomentodiplacone and 3 ?-O-methyl-5 ?-hydroxydiplacone, have been isolated from chloroform part of ethanol extract of P. tomentosa fruits. Several chromatographic methods, including classic column chromatography, TLC, analytical and preparative HPLC were applied in the separation and isolation process. The structures of isolated compounds were determined using different spectral methods (UV, IR, MS and NMR). The cytotoxic effect was assessed in vitro on the model of THP-1 human leukemic monocytes using WST-1 and LDH assay. A newly isolated flavone with unsubstituted C-geranyl side chain has shown a potent cytotoxic effect with IC50 4.5 ? 1.2 ?M. The cytotoxic activity of flavanones with cyclized C-geranyl moiety was lower. Furthermore, the non-toxic concentrations of compounds were used for evaluation of anti/pro-oxidant and anti-inflammatory properties. The antioxidant activity against the generation of reactive oxygen species in pyocyanin-stimulated monocytes has been assessed by measurement of fluorescent 2 ?,7 ?-dichlorofluorescein (DCF) product. Whereas the geranyl side chain and its substitution play a substantial role in the cytotoxic action of flavonoids, these two aspects have only a small impact on their antioxidant properties. Positional arrangement of substituents on the flavonoid skeleton seems to be more important. Our investigation of antioxidant properties has confirmed this thesis. Moreover, the ability to attenuate the activation of transcriptional factors NF?B/AP-1 implicated in inflammatory processes has been evaluated on the model of THP1-XBlueTM-MD2-CD14 cells. Lipopolysaccharide (LPS) stimulation of TLR4 receptors in this cell line induced signaling cascades leading to the activation of NF-?B and AP-1 and the subsequent production of SEAP reporter protein was measured. Two novel flavanones have shown the capability to decrease the activity of NF?B/AP-1 in statistically significant manner. The phytochemical analysis and biological activity testing of novel geranyl flavonoids have extended the existent knowledge about constituents isolated from P. tomentosa species

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10611 - Plant sciences, botany

Projekt

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Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů