Neurochemistry international
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Diabetic neuropathy (DN) is a common form of peripheral neuropathy, yet the mechanisms responsible for chronic pain in this disease are poorly understood. The up-regulation of the expression and function of voltage-gated sodium channel Nav1.7 has been implicated in DN, however, the exact mechanism is unclear. In the present study, we found that a proportion of streptozotocin (STZ)-treated rats suffered from mechanical allodynia and thermal hyperalgesia for a long-lasting time. ⋯ Intrathecal injection of NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) significantly attenuated the pain behaviors and over-expression of Nav1.7 in DRG neurons. These data suggest that increased TNF-α may be responsible for up-regulation of Nav1.7 in DRG neurons of rats with DN, and NF-κB signal pathway is involved in this process. The findings might provide potential target for preventing diabetic neuropathy.
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Sodium salicylate (SS) confers neuroprotection in various models of Parkinson's disease (PD) but the mechanisms behind its protective actions are not clear. PD pathology is multifactorial involving numerous processes such as protein aggregation, dysfunction of protein degradation machinery and apoptosis. Detailed evaluation of effects of SS on these processes can provide an insight into the mechanism of neuroprotection by SS in PD pathology. ⋯ Since astrocytes are involved in maintenance of glutathione (GSH) homeostasis, it resulted in a concomitant improvement in the GSH levels. As a result, decrease in apoptosis as indicated by caspase-9 and caspase-3 expression as well as TUNEL assay was also observed in the SS conjunction group. Our results indicate that besides being a known free radical scavenger and anti-inflammatory compound, SS can provide neuroprotection by differently upregulating the HSPs and reducing the protein aggregation burden.
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Although the etiology of PD remains unclear, increasing evidence has shown that oxidative stress plays an important role in its pathogenesis and that of other neurodegenerative disorders. The phenolic glucoside gastrodin, a main constituent of a Chinese herbal medicine Gastrodia elata (GE) Blume, has been known to display antioxidant activity. The present study aimed to investigate the protective effects of gastrodin on 1-methyl-4-phenylpyridinium (MPP(+))-induced oxidative cytotoxicity in human dopaminergic SH-SY5Y cells and the underlying mechanism for this neuroprotection. ⋯ We also demonstrated that the specific p38 MAPK inhibitor, SB203580, concentration-dependently blocked on gastrodin-induced HO-1 expression, and meanwhile SB203580 reversed the protective effect of gastrodin against MPP(+)-induced cell death. Taken together, these findings suggest that gastrodin can induce HO-1 expression through activation of p38 MAPK/Nrf2 signaling pathway, thereby protecting the SH-SY5Y cells from MPP(+)-induced oxidative cell death. Thus our study indicates that gastrodin has a partial cytoprotective role in dopaminergic cell culture systems and could be of importance for the treatment of PD and other oxidative stress-related diseases.
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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.