Metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) has been implicated in the pathogenesis of Parkinson’s disease (PD). In addition, resveratrol was shown to regulate the expression of MALAT1. Therefore, the objective of this study was to clarify the role of resveratrol in PD. During the study, luciferase assays were conducted to determine the effect of resveratrol on the transcription efficiency of MALAT1 promoter as well as the regulatory relationships among MALAT1, miR‐129, and SNCA. In addition, real‐time PCR, Western blot analysis, MTT and flow cytometry analyses were conducted to investigate the mechanism of resveratrol in PD. Furthermore, a PD mouse model was established to study the role of resveratrol in vivo. It was found that resveratrol increased the number of TH+ cells and the expression of miR‐129, while decreasing the expression of MALAT1 and SNCA. In addition, MALAT1 inhibited the expression of miR‐129, a negative regulator of SNCA, thus increasing the expression of SNCA. A further mechanistic study revealed that resveratrol inhibited MALAT1 expression by blocking the transcription of the MALAT1 promoter. Finally, MPTP treatment could decrease cell proliferation and increase cell apoptosis, while resveratrol could partly offset the effect of MPTP. In summary, the therapeutic effect of resveratrol in the treatment of PD can be attributed to its ability to modulate the MALAT1/miR‐129/SNCA signaling pathway.
Acteoside (ACT) has been shown to exert antioxidant and neuroprotective effects in neurodegenerative diseases. However, the effect of ACT on cerebral ischemia-reperfusion (I/R) injury is not yet clear. In this study, we found that ACT administration reduced infarct volume and brain edema, and improved neurological deficits, as indicated by the decreased modified neurological severity score. Administration of ACT strikingly reduced oxidative stress, accompanied by decreased levels of reactive oxygen species and malondialdehyde and increased levels of superoxide dismutase and catalase in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). Furthermore, ACT administration reduced the number of terminal deoxynucleotidyl transferase uridine 5′-triphosphate (UTP) nick-end labeling-positive cells in the cerebral cortex of ischemic side of MCAO/R rats, accompanied by downregulation of B cell lymphoma 2 (Bcl-2) associated X protein and cleaved caspase-3 proteins and upregulation of Bcl-2 protein. Additionally, ACT treatment inhibited the protein kinase R/eukaryotic initiation factor-2α stress pathway in the brains of MCAO/R rats. Our results demonstrated that ACT attenuates oxidative stress and neuronal apoptosis in MCAO/R rats, suggesting that ACT may serve as a novel therapeutic candidate for the treatment of I/R brain injury.
7,8-dihydroxyflavone (7,8-DHF) is a recently identified potent agonist of tropomyosin-related kinase B that can cross the blood-brain barrier after oral or intraperitoneal administration. The aim of the present study was to determine whether 7,8-DHF has neuroprotective effects against cerebral ischemia and reperfusion (I/R) injury and, if so, to investigate the possible underlying mechanisms. Cerebral I/R injury rats were induced by middle cerebral artery occlusion for 90 min followed by reperfusion for 24 h. 7,8-DHF was administered intraperitoneally at a dose of 5 mg/kg immediately after ischemia. Our results showed that 7,8-DHF significantly reduced neurological deficit scores, infarct volumes, and neuronal apoptosis in brains of I/R rats. Meanwhile, 7,8-DHF also increased Bcl-2 expression, decreased expression of cleaved caspase-3, Bax and inducible nitric oxide synthase, and inhibited nuclear factor-κB activation in ischemic cortex. Finally, malondialdehyde and nitric oxide contents were reduced, but activities of glutathione, glutathione peroxidase and superoxide dismutase were restored in ischemic cortex treated with 7,8-DHF. Taken together, our findings demonstrated that 7,8-DHF is able to protect against cerebral I/R injury, which may be, at least in part, attributable to its anti-apoptotic, anti-oxidative and anti-inflammatory actions.
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