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1.
Metab Brain Dis ; 33(1): 167-175, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29101599

RESUMO

Anxiety disorder is a serious and burdensome psychiatric illness that frequently turn into chronic clinical conditions. Puerarin have been shown to be effective in the therapy of depression. However, few studies are concerned about the anxiolytic-like effects of puerarin. The current study aimed to evaluate the anxiolytic-like effects of puerarin and its possible mechanism. To evaluate this, the behavioral tests, i.e. Vogel-type conflict test (VTCT), elevated plus-maze test (EPMT), and open-field test (OFT) were conducted. Data showed that similar to the positive-control drug sertraline (Ser) (15 mg/kg, i.g.), the anxiolytic-like effects were produced by puerarin (60 and 120 mg/kg, i.g.) in VTCT and EMPT respectively without affecting locomotor activity in OFT. Moreover, the present study also found that consistent with Ser, the levels of allopregnanolone and serotonin (5-HT) in the prefrontal cortex and hippocampus were increased by puerarin (60 and 120 mg/kg, i.g.), respectively. In summary, the present study indicated that puerarin exerted the anxiolytic-like effects, which maybe associated with normalization of 5-HT levels and biosynthesis of allopregnanolone in brain.


Assuntos
Ansiolíticos/farmacologia , Ansiedade/tratamento farmacológico , Encéfalo/metabolismo , Isoflavonas/farmacologia , Neurotransmissores/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Depressão/tratamento farmacológico , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Pregnanolona/farmacologia , Ratos Sprague-Dawley , Serotonina/metabolismo
2.
Sci Rep ; 7(1): 6266, 2017 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-28740098

RESUMO

The present study aimed to investigate the mechanisms underlying the antidepressant-like effects of puerarin via the chronic unpredictable stress (CUS) procedure in rats. Similar to Sertraline (Ser), Chronic treatment of puerarin (60 and 120 mg/kg, i.g) elicited the antidepressant-like effects by reversing the decreased sucrose preference in sucrose preference test (SPT), by blocking the increased latency to feed in novelty-suppressed feeding test (NSFT) and the increased immobility time in forced swimming test (FST) without affecting locomotor activity. However, acute puerarin treatment did not ameliorate the antidepressant- and anxiolytic- like effects in FST and NSFT, respectively. In addition, enzyme linked immunosorbent assay (ELISA) and high performance liquid chromatography-electrochemical detection (HPLC-ECD) showed that chronic treatment of puerarin (60 and 120 mg/kg, i.g) reversed the decreased levels of progesterone, allopregnanolone, serotonin (5-HT) and 5-Hydroxyindoleacetic acid (5-HIAA) in prefrontal cortex and hippocampus of post-CUS rats. Furthermore, puerarin (60 and 120 mg/kg, i.g) blocked the increased corticotropin releasing hormone (CRH), corticosterone (Cort) and adrenocorticotropic hormone (ACTH). Collectively, repeated administration of puerarin alleviated the behavioral deficits induced by chronic stress which was associated with the biosynthesis of neurosteroids, normalization of serotonergic system and preventing HPA axis dysfunction.


Assuntos
Comportamento Animal/efeitos dos fármacos , Isoflavonas/farmacologia , Estresse Psicológico/complicações , Estresse Psicológico/tratamento farmacológico , Vasodilatadores/farmacologia , Animais , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Locomoção , Masculino , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/fisiopatologia , Natação
3.
Acta Pharmacol Sin ; 38(12): 1632-1641, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28713162

RESUMO

Both the anti- and pro-apoptotic members of the Bcl-2 family are regulated by a conserved Bcl-2 homology (BH3) domain. ABT-263 (Navitoclax), a novel BH3 mimetic and orally bioavailable Bcl-2 family inhibitor with high affinity for Bcl-xL, Bcl-2 and Bcl-w has entered clinical trials for cancer treatment. But the anticancer mechanisms of ABT-263 have not been fully elucidated. In this study we investigated the effects of ABT-263 on human esophageal cancer cells in vitro and to explore its anticancer mechanisms. Treatment with ABT-263 dose-dependently suppressed the viability of 3 human esophageal cancer cells with IC50 values of 10.7±1.4, 7.1±1.5 and 8.2±1.6 µmol/L, in EC109, HKESC-2 and CaES-17 cells, respectively. ABT-263 (5-20 µmol/L) dose-dependently induced G1/G0-phase arrest in the 3 cancer cell lines and induced apoptosis evidenced by increased the Annexin V-positive cell population and elevated levels of cleaved caspase 3, cleaved caspase 9 and PARP. We further demonstrated that ABT-263 treatment markedly increased the expression of p21Waf1/Cip1 and decreased the expression of cyclin D1 and phospho-Rb (retinoblastoma tumor suppressor protein) (Ser780) proteins that contributed to the G1/G0-phase arrest. Knockdown of p21Waf1/Cip1 attenuated ABT-263-induced G1/G0-phase arrest. Moreover, ABT-263 treatment enhanced pro-survival autophagy, shown as the increased LC3-II levels and decreased p62 levels, which counteracted its anticancer activity. Our results suggest that ABT-263 exerts cytostatic and cytotoxic effects on human esophageal cancer cells in vitro and enhances pro-survival autophagy, which counteracts its anticancer activity.


Assuntos
Compostos de Anilina/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Sulfonamidas/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Relação Estrutura-Atividade , Células Tumorais Cultivadas
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