Resveratrol Promotes Autophagy to Improve neuronal Injury in Parkinson's Disease by Regulating SNHG1/miR-128-3p/SNCA Axis.

BACKGROUND: Parkinson's disease (PD) is seriously threatening the health and life quality of the elderly, who have a high incidence and high disability rate. Resveratrol (RES) was reported to play a protective role in PD. However, the functions and potential mechanism of RES in PD remain unclear, which need to be further explored. METHODS: Human neuroblastoma cells (SH-SY5Y and SK-N-SH) were subjected to 1-Methyl-4-phenylpyridium (MPP+) induction to construct a cell model of PD. Cell viability was evaluated using CCK-8. The gene expression was evaluated using qRT-PCR and western blot. Luciferase activity assay and RIP were performed to validate interactions among SNHG1, miR-128-3p and SNCA. RESULTS: Our results exhibited that RES reduced SNHG1 and SNCA expression but elevated miR-128-3p expression in human neuroblastoma cells upon MPP+ induction. Functionally, RES resulted in the promotion of cell autophagy in MPP+-induced human neuroblastoma cells, while these influences were abolished by SNHG1 overexpression. Mechanistically, SNHG1 could indirectly elevate SNCA expression via sponging miR-128-3p. Moreover, SNCA overexpression reversed SNHG1 silencing-induced cell autophagy in MPP+-induced human neuroblastoma cells upon RES pre-incubation. CONCLUSIONS: RES prevented MPP+-induced repression of cell autophagy through inhibiting the SNHG1/miR-128-3p/SNCA axis, suggesting that RES might play a preventive effect on PD progression.

Protective Effects of Ursodeoxycholic Acid Against Oxidative Stress and Neuroinflammation Through Mitogen-Activated Protein Kinases Pathway in MPTP-Induced Parkinson Disease.

OBJECTIVES: Parkinson disease (PD) is the second most common neurodegenerative disorder, and no disease-modifying medications are available. Ursodeoxycholic acid (UDCA) has been shown to prevent neuronal damage; however, the effect of UDCA on PD is unclear. This study aimed to the role of UDCA on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. METHODS: Mice were divided into 3 experimental groups: the control group, MPTP group, and UDCA-treat group. Mice were tested for behavioral impairments, and slices at the level of the ventral midbrain were collected to perform hematoxylin and eosin and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining and immunohistochemistry. To evaluate the levels of dopamine (DA), serotonin (5-HT), antioxidant markers, and inflammatory cytokines, enzyme-linked immunoassays were carried out. The protein (α-synuclein, p38, phospho-p38, c-Jun N-terminal kinase [JNK], and phospho-JNK) expression was examined adopting Western blot. RESULTS: We found that UDCA reduced the MPTP-induced degeneration of DA neurons, improved behavioral impairments, and decreased the protein level of α-synuclein, accompanied with increases of DA and 5-HT. In the present study, UDCA prevented DA neurons from MPTP toxicity with increased superoxide dismutase, catalase, glutathione, and decreased malondialdehyde levels. Ursodeoxycholic acid prevented DA neurons from MPTP toxicity with decreased levels of tumor necrosis factor α, interferon γ, and interleukin (IL)-1ß, IL-6, and IL-10. Our results demonstrated that UDCA inhibited the phosphorylation of JNK and p38MAPK. CONCLUSIONS: This study revealed protective effects of UDCA against oxidative stress and neuroinflammation through mitogen-activated protein kinases pathways in MPTP-induced PD, suggesting that UDCA may be a novel therapeutic candidate for PD.

Effect of Melatonin and Resveratrol against Memory Impairment and Hippocampal Damage in a Rat Model of Vascular Dementia.

OBJECTIVES: This study was intended to investigate whether treatment with resveratrol and melatonin alone or in combination can exert neurorestorative effects in a rat model of vascular dementia. METHODS: Briefly, male Wistar rats were subjected to permanent bilateral common carotid artery occlusion (BCCAO) by surgery. After 4 weeks, the cognitive deficits were assessed using the Morris water maze and novel object recognition tests. The biochemical parameters of oxidative stress and inflammation were also assessed. RESULTS: Rats in the BCCAO group showed cognitive deficits, accompanied by oxidonitrosative stress, neuroinflammation, and a reduction in brain-derived neurotrophic factor (BDNF) in the hippocampus region. Moreover, the acetylcholinesterase activity in the hippocampus was found to be increased in the BCCAO group compared to the sham group. The 4-week treatment with melatonin (10 mg/kg) and resveratrol (20 mg/kg) alone and in combination (melatonin 5 mg/kg and reseveratrol 10 mg/kg) caused a significant improvement in the cognitive deficits induced by BCCAO, accompanied by a reversal of oxidonitrosative stress, neuroinflammation, and BDNF depletion in the hippocampus region. Additionally, the treatment with melatonin and resveratrol significantly decreased acetylcholinesterase activity compared to in the BCCAO group. Melatonin and resveratrol ameliorated the BDNF expression of hippocampal protein. CONCLUSION: These results emphasize that coadministration of melatonin and resveratrol can be beneficial in BCCAO-induced vascular dementia through changes in BDNF expressions.