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J Reprod Immunol ; 144: 103272, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33465522

RESUMEN

Radioprotective effects of Resveratrol is well known in normal cells exposed to the damaging effects of ionizing radiation however, its potential radioprotective effect on ovarian follicle formation and development is still uncertain. Astonishingly, it has been reported that PARP contributed to the pathogenesis of immune-mediated ovarian injury. In this paper, Resveratrol was tested for its inflammatory, anti-cervical carcinoma activity, and checked its targets poly (ADP-ribose) polymerase 1 (PARP-1) induced premature ovarian failure with a potent enzymatic modulatory activity. Through high-throughput virtual screening method, Resveratrol was screened to find its target. That the compound strongly inhibited cervical carcinoma HT-3 cell. The cell proliferation was evaluated by an CCK-8 assay, and the cell apoptosis was assessed by a flow cytometry. Rat model of premature ovarian failure was used to introduce resveratrol preparation and rtPCR was done to measure expression of apoptosis related markers. We report resveratrol as a potential target for PARP-1 and its modulator from a high-throughput virtual screening method. Resveratrol was measured its anti-cervical carcinoma activity by using an CCK-8 assay, which suggested that the compound strongly inhibited HT-3 cell proliferation, the IC50 value is 0.65 µM. In addition, the compound induced HT-3 cell apoptosis in a dose-response manner. Resveratrol preserves the entire ovarian follicle pool manifested by increasing serum anti-Müllerian hormone (AMH) levels. Study suggest that resveratrol restored ovarian function through increasing AMH levels, and diminishing ovarian inflammation, predominantly modulation of PPAR-1 and inhibition of inflammatory cytokines. Resveratrol was identified targets for PARP-1 from a high-throughput virtual screening method, strongly inhibited PARP-1 protein and HT-3 cell proliferation. Resveratrol is a promising PARP-1 modulator with anti-cervical carcinoma activity, which deserves further investigation.


Asunto(s)
Carcinoma/tratamiento farmacológico , Poli(ADP-Ribosa) Polimerasa-1/antagonistas & inhibidores , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Insuficiencia Ovárica Primaria/tratamiento farmacológico , Resveratrol/farmacología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Animales , Hormona Antimülleriana/sangre , Apoptosis/efectos de los fármacos , Carcinoma/inmunología , Carcinoma/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Citocinas/antagonistas & inhibidores , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Ensayos Analíticos de Alto Rendimiento , Humanos , Simulación del Acoplamiento Molecular , Folículo Ovárico/efectos de los fármacos , Folículo Ovárico/inmunología , Folículo Ovárico/patología , Folículo Ovárico/efectos de la radiación , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Insuficiencia Ovárica Primaria/sangre , Insuficiencia Ovárica Primaria/inmunología , Ratas , Resveratrol/uso terapéutico , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/patología , Irradiación Corporal Total/efectos adversos
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