Neurochemistry international
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Sulfuretin, a potent anti-oxidant, has been thought to provide health benefits by decreasing the risk of oxidative stress-related diseases. In this study, we investigated the mechanisms of sulfuretin protection of neuronal cells from cell death induced by the Parkinson's disease (PD)-related neurotoxin 6-hydroxydopamine (6-OHDA). We examined whether sulfuretin acts as an anti-oxidant to reduce oxidative stress and mitochondrial-mediated apoptotic cascade events in 6-OHDA-induced neurotoxicity in SH-SY5Y cells. ⋯ Eventually, sulfuretin inhibited 6-OHDA-induced NF-κB translocation to the nucleus induced by 6-OHDA. The results of the current study provide the first evidence that sulfuretin protects SH-SY5Y cells against 6-OHDA-induced neuronal cell death, possibly through inhibition of phosphorylation of MAPK, PI3K/Akt, and GSK-3β, which leads to mitochondrial protection, NF-κB modulations and subsequent suppression of apoptosis via ROS-dependent pathways. Thus, we conclude that sulfuretin may have a potential role for neuroprotection and, therefore, may be used as a therapeutic agent for PD.
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Piperine reverses the effects of corticosterone on behavior and hippocampal BDNF expression in mice.
A mouse model of depression has been recently developed by exogenous corticosterone administration. The present study aimed to examine the antidepressant-like effect and the possible mechanisms of piperine, a major alkaloid of black pepper (Piper nigrum Linn.) and long pepper (Piper longum Linn.), in corticosterone-induced depression in mice. ⋯ Treating the animals with piperine significantly suppressed behavioral and biochemical changes induced by corticosterone. The results suggest that piperine produces an antidepressant-like effect in corticosterone-treated mice, which is possibly mediated by increasing brain-derived neurotrophic factor expression in the hippocampus.
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Na(+)/H(+) exchanger NHE6/SLC9A6 is an X-linked gene that is widely expressed and especially abundant in brain, heart and skeletal muscle where it is implicated in endosomal pH homeostasis and trafficking as well as maintenance of cell polarity. Recent genetic studies have identified several mutations in the coding region of NHE6 that are linked with severe intellectual disability, autistic behavior, ataxia and other abnormalities. One such defect consists of an in-frame deletion of three amino acids ((370)Trp-Ser-Thr(372), ΔWST) that adjoin the predicted ninth transmembrane helix of the exchanger. ⋯ Similarly, in transfected primary mouse hippocampal neurons, wild-type NHE6 was localized in discrete puncta throughout the soma and neurites, whereas the ΔWST mutant displayed a diffuse reticular pattern. Remarkably, the extensive dendritic arborization observed in neurons expressing wild-type NHE6 was noticeably diminished in ΔWST-transfectants. These results suggest that deletion of (370)Trp-Ser-Thr(372) leads to endoplasmic reticulum retention and loss of NHE6 function which potentially impacts the trafficking of other membrane-bound cargo and cell polarity.