stilbenes and Parkinson-Disease--Secondary

Parkinson's disease (PD) was one of the most common neurodegenerative diseases with a slow and progressive loss of dopamine (DA) neurons in the midbrain substantia nigra (SN). Neuroinflammation was identified to be an important contributor to PD pathogenesis with the hallmark of microglia activation. Tetrahydroxystilbene glucoside (TSG) was the main active component extracted from

Topics: Animals; Dopamine; Glucosides; Male; Neuroprotective Agents; Neurotoxicity Syndromes; Oxidopamine; Parkinson Disease, Secondary; Random Allocation; Rats; Stilbenes

The accumulation of misfolded α-synuclein in dopaminergic neurons is the leading cause of Parkinson's disease (PD). Resveratrol (RV), a polyphenolic compound derived from grapes and red wine, exerts a wide range of beneficial effects via activation of sirtuin 1 (SIRT1) and induction of vitagenes. Here, we assessed the role of RV in a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) induced mouse model of PD and explored its potential mechanisms.. RV and EX527, a specific inhibitor of SIRT1, were administered before and after MPTP treatment. RV protected against MPTP-induced loss of dopaminergic neurons, and decreases in tyrosine hydroxylase and dopamine levels, as well as behavioral impairments. Meanwhile, RV administration activated SIRT1. Microtubule-associated protein 1 light chain 3 (LC3) was then deacetylated and redistributed from the nucleus to the cytoplasm, which provoked the autophagic degradation of α-synuclein in dopaminergic neurons. Furthermore, EX527 antagonized the neuroprotective effects of RV by reducing LC3 deacetylation and subsequent autophagic degradation of α-synuclein.. We showed that RV ameliorated both motor deficits and pathological changes in MPTP-treated mice via activation of SIRT1 and subsequent LC3 deacetylation-mediated autophagic degradation of α-synuclein. Our observations suggest that RV may be a potential prophylactic and/or therapeutic agent for PD.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Acetylation; alpha-Synuclein; Animals; Autophagy; Behavior, Animal; Corpus Striatum; Disease Models, Animal; Dopamine; Male; Mice, Inbred C57BL; Microtubule-Associated Proteins; Neuroprotective Agents; Parkinson Disease, Secondary; Resveratrol; Sirtuin 1; Stilbenes

This study investigated the neuroprotective effects of resveratrol (RVT)-loaded polysorbate 80 (PS80)-coated poly(lactide) nanoparticles in a mouse model of Parkinson's disease (PD), and compared these effects with those from bulk RVT.. C57BL/6 mice received for 15 days RVT intraperitoneally (nanoparticulate or non-nanoparticulate), as well as single intranasal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that damages dopaminergic neurons and induces PD-related symptoms.. MPTP induced significant impairments on olfactory discrimination and social recognition memory, as well as caused striatal oxidative stress and reduced the expression of tyrosine hydroxylase in striatum. RVT-loaded nanoparticles (but not bulk) displayed significant neuroprotection against MPTP-induced behavioral and neurochemical changes.. These results point to RVT-loaded poly(lactide)-nanoparticles coated with PS80 a promising nanomedical tool and adjuvant therapy for PD.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Antioxidants; Corpus Striatum; Dopaminergic Neurons; Drug Carriers; Male; Memory; Mice; Mice, Inbred C57BL; Neuroprotective Agents; Olfactory Perception; Oxidative Stress; Parkinson Disease, Secondary; Polyesters; Polysorbates; Resveratrol; Stilbenes

Resveratrol is a natural polyphenol and possesses many biological functions such as anti-inflammatory activity and protection against atherosclerosis and myocardial infraction. Parkinson's disease is a common progressive neurodegenerative disease. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is the most useful neurotoxin to induce Parkinsonism. The present study was carried out to elucidate the neuroprotective effect and possible mechanism of resveratrol on MPTP-induced striatal neuron loss. Sixty adult Balb/c mice were divided into four groups: sham operation, MPTP treatment (30 mg/kg, i.p.), MPTP combined with resveratrol administration (20 mg/kg, i.v.), and resveratrol treatment alone. Microdialysis and high-performance liquid chromatography were used to analyze dihydroxybenzoic acid (DHBA) that reflected the hydroxyl radical level. In the present study, we found MPTP chronic administration significantly induced motor coordination impairment in mice. After MPTP administration, the hydroxyl radical levels in substantia nigra were also significantly elevated and animals displayed severe neuronal loss. Resveratrol administration significantly protected mice from MPTP-induced motor coordination impairment, hydroxyl radical overloading, and neuronal loss. Our results demonstrated that resveratrol could elicit neuroprotective effects on MPTP-induced Parkinsonism through free radical scavenging.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Ataxia; Corpus Striatum; Free Radical Scavengers; Hand Strength; Male; Mice; Mice, Inbred BALB C; Motor Activity; Neurons; Neuroprotective Agents; Parkinson Disease, Secondary; Resveratrol; Stilbenes