RESUMEN
Cellular senescence influences tumor suppression and progress, tissue repair and regeneration, tissue and organismal aging, and age-related diseases. Aging intervention might be an advantageous target for prevention and treatment of diverse age-related diseases. In this study, we investigated whether (-)-loliolide purified from the crude extract of Polygonum aviculare exerted inhibitory activity against cellular senescence in human dermal fibroblasts (HDFs). (-)-Loliolide diminished senescence-associated ß-galactosidase activity (SA-ß-gal), the level of p21 protein, and the level of reactive oxygen species in senescent cells induced by adriamycin treatment. (-)-Loliolide also attenuated SA-ß-gal activity in HDFs under replicative senescence. These findings imply that (-)-loliolide rescues cellular senescence in HDFs and might be useful for the development of dietary supplements or cosmetics that ameliorate tissue aging or age-associated diseases.
Asunto(s)
Benzofuranos/farmacología , Senescencia Celular/efectos de los fármacos , Dermis/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Extractos Vegetales/farmacología , Polygonum , Benzofuranos/química , Benzofuranos/aislamiento & purificación , Senescencia Celular/fisiología , Dermis/citología , Dermis/fisiología , Relación Dosis-Respuesta a Droga , Fibroblastos/fisiología , Humanos , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificaciónRESUMEN
Cellular senescence is known to contribute to tissue aging, a variety of age-related diseases, tissue regeneration, and cancer. Therefore, aging intervention might be useful for prevention of aging as well as age-related disease. In this study, we investigated compounds from Polygonum aviculare to determine if they inhibited cellular senescence in human primary cells, human dermal fibroblasts (HDFs) and human umbilical vein endothelial cells (HUVECs). Ten compounds from P. aviculare were purified and their inhibitory effects on adriamycin-induced cellular senescence were measured by observing senescence-associated ß-galactosidase (SA-ß-gal) activity and reactive oxygen species. Among them, compound 9 (quercetin-3-O-ß-D-glucuronide) showed inhibitory effects against cellular senescence in HDFs and HUVECs treated with adriamycin. Additionally, compound 9 rescued replicative senescence in HDFs and HUVECs. These data imply that compound 9 represses cellular senescence in human primary cells and might be useful for the development of dietary supplements or cosmetics that ameliorate tissue aging or aging-associated diseases.
Asunto(s)
Antioxidantes/farmacología , Senescencia Celular/efectos de los fármacos , Descubrimiento de Drogas , Endotelio Vascular/efectos de los fármacos , Quercetina/análogos & derivados , Envejecimiento de la Piel/efectos de los fármacos , Piel/efectos de los fármacos , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Etnofarmacología , Glucurónidos/química , Glucurónidos/aislamiento & purificación , Glucurónidos/farmacología , Células Endoteliales de la Vena Umbilical Humana/citología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , Medicina Tradicional Coreana , Estructura Molecular , Concentración Osmolar , Componentes Aéreos de las Plantas/química , Polygonum/química , Quercetina/química , Quercetina/aislamiento & purificación , Quercetina/farmacología , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Piel/citología , Piel/metabolismo , beta-Galactosidasa/antagonistas & inhibidores , beta-Galactosidasa/metabolismoRESUMEN
Cellular senescence contributes to tissue and organismal aging, tumor suppression and progress, tissue repair and regeneration, and age-related diseases. Thus, aging intervention might be a promising target for treatment and prevention of diverse age-related diseases. In the present study, we investigated whether juglanin purified from the crude extract of Polygonum aviculare exerted inhibitory activity against cellular senescence in human dermal fibroblasts (HDFs). Juglanin decreased senescence-associated ß-galactosidase activity (SA-ß-gal) and the level of reactive oxygen species in senescent cells induced by adriamycin treatment. Juglanin also repressed SA-ß-gal activity in HDFs under replicative senescence. These results suggest that juglanin represses cellular senescence in HDFs and might be useful for the development of dietary supplements or cosmetics that alleviate tissue aging or age-related diseases.
Asunto(s)
Senescencia Celular/efectos de los fármacos , Glicósidos/farmacología , Quempferoles/farmacología , Células Cultivadas , Dermis/citología , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Glicósidos/química , Glicósidos/aislamiento & purificación , Humanos , Quempferoles/química , Quempferoles/aislamiento & purificación , Polygonum/química , Especies Reactivas de Oxígeno/metabolismo , beta-Galactosidasa/metabolismoRESUMEN
To investigate the putative mediation of peripheral benzodiazepine receptor (PBR) in the cytotoxicity of flavonoids, in this study, modulatory effects of several flavonoids on the lipid peroxide (LPO) production and PBR mRNA expression of human neuroblastoma cells were observed. Elevated levels of peroxidated products in cancer cells may activate pro-apoptotic and anti-proliferative signaling pathways. Treatment of 10(-6) M 4'-chlorodiazepam and PK 11195 ligands of the PBR for 6 days enhanced the generation of LPO of the human neuroblastoma cells. Several flavonoids, well-known cytotoxic substances, potentiated the enhancement of LPO production by PBR ligands. Treatment of 10(-6) M flavonoids for 6 days elevated the expression of PBR mRNA in cells. These findings indicate that the potential of flavonoids to induce apoptosis in cancer cells is strongly associated with their PBR-inducing properties, thereby providing a new mechanism by which polyphenolic compounds may exert their cancer-preventive and anti-neoplastic effects.