RESUMEN
The present study aimed to investigate whether apigenin elicits antidepressant effects in depressantlike mice via the regulation of autophagy. The depressantlike behaviors were established in a chronic restraint stress model. Male BALB/c mice were subjected to restraint stress for 6 h/day for a period of 21 days, and deficits in sucrose preference, tail suspension and forced swim tests were confirmed to be improved following oral apigenin. To investigate the underlining mechanisms, the hippocampal levels of p62 and microtubuleassociated protein light chain 3II/I (LC3II/I) were measured using western blot analysis. The expression levels of LC3II/I and p62 indicated that the significantly inhibited autophagy level induced by chronic restraint stress can be increased following apigenin treatment. Similar to the level of autophagy, the expression levels of adenosine monophosphateactivated protein kinase (AMPK) and Unc51 like autophagy activating kinase1 were downregulated after chronic restraint stress stimulation and, subsequently upregulated following treatment with apigenin. Conversely, the levels of mammalian target of rapamycin (mTOR) were increased in chronic restraint stress mice and inhibited by apigenin. Collectively, the present findings indicated that apigenin potentially promotes autophagy via the AMPK/mTOR pathway and induces antidepressive effects in chronic restraint stress mice.
Asunto(s)
Antidepresivos/uso terapéutico , Apigenina/uso terapéutico , Autofagia/efectos de los fármacos , Depresión/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Quinasas de la Proteína-Quinasa Activada por el AMP , Animales , Antidepresivos/farmacología , Apigenina/farmacología , Homólogo de la Proteína 1 Relacionada con la Autofagia/metabolismo , Depresión/metabolismo , Masculino , Ratones Endogámicos BALB C , Proteínas Quinasas/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Chronic renal failure (CRF) is a major public health problem worldwide. Hydrogen sulfide (H2S) plays important roles in renal physiological and pathophysiological processes. However, whether H2S could protect against CRF in rats remains unclear. In this study, we found that H2S alleviated gentamicin-induced nephrotoxicity by reducing reactive oxygen species (ROS)-mediated apoptosis in normal rat kidney-52E cells. We demonstrated that H2S significantly improved the kidney structure and function of CRF rats. We found that H2S decreased the protein levels of Bax, Caspase-3, and Cleaved-caspase-3, but increased the expression of Bcl-2. Treatment with H2S reduced the levels of malondialdehyde and ROS and increased the activities of superoxide dismutase and glutathione peroxidase. H2S significantly abolished the phosphorylation of extracellular signal-regulated protein kinase 1/2, c-Jun N-terminal kinase, and p38 in the kidney of CRF rats. Furthermore, H2S decreased the expression levels of tumor necrosis factor-α, interleukin (IL)-6, IL-10, and monocyte chemoattractant protein-1, as well as the protein levels of p50, p65, and p-p65 in the kidney of CRF rats. In conclusion, H2S could ameliorate adenine-induced CRF in rats by inhibiting apoptosis and inflammation through ROS/mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways.