lignans and Parkinsonian-Disorders

The present study investigated the effects of (-)-sesamin on motor and memory deficits in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of Parkinson's disease (PD) with l-3,4-dihydroxyphenylalanine (l-DOPA). MPTP-lesioned (30mg/kg/day, 5days) mice showed deficits in memory including habit learning memory and spatial memory, which were further aggravated by daily treatment with 25mg/kg l-DOPA for 21days. However, daily treatment with (-)-sesamin (25 and 50mg/kg) for 21days ameliorated memory deficits in an MPTP-lesioned mouse model of PD treated with l-DOPA (25mg/kg). Both (-)-sesamin doses reduced decreases in the retention latency time in the passive avoidance test, latency to fall of rotarod test and distance traveled in the open field test, and attenuated decreases in tyrosine hydroxylase (TH)-immunopositive cells, dopamine, and its metabolites in the substantia nigra-striatum. (-)-Sesamin reduced increases in the retention transfer latency time in the elevated plus-maze test and N-methyl-d-aspartate receptor (NMDAR) expression and reduced decreases in the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-response element binding protein (CREB) in the hippocampus. In contrast, daily treatment with 10mg/kg l-DOPA for 21days ameliorated memory deficits in MPTP-lesioned mice, and this effect was further improved by treatment with (-)-sesamin (25 and 50mg/kg). These results suggest that (-)-sesamin protects against habit learning memory deficits by activating the dopamine neuronal system, while spatial memory deficits are decreased by its modulatory effects on the NMDAR-ERK1/2-CREB system. Accordingly, (-)-sesamin may act as an adjuvant phytonutrient for motor and memory deficits in patients with PD receiving l-DOPA.

Topics: Animals; Antiparkinson Agents; Avoidance Learning; Corpus Striatum; Dioxoles; Dopamine; Dose-Response Relationship, Drug; Levodopa; Lignans; Male; Memory; Memory Disorders; Mice, Inbred C57BL; Motor Activity; Nootropic Agents; Parkinsonian Disorders; RNA, Messenger; Substantia Nigra

MiR-34 family members have been previously shown to play potential functional role in Parkinson's disease (PD) pathogenesis. However, the regulatory role of miR-34a has not been demonstrated in PD yet. This study aims to clarify the potential neuroprotective effect of Schisandrin B (Sch B) involving miR-34a function in 6-OHDA-induced PD model.. The expression changes of miR-34a and Nrf2 pathway related genes were detected in 6-OHDA-treated SH-SY5Y cells under Sch B pretreatment. Cell viability and PD feathers of 6-OHDA-induced PD mice were measured for neuroprotection assessment. The regulation of miR-34a on Nrf2 activity and expression was demonstrated through gain-of-function and loss-of-function studies, while the regulatory role of miR-34a in the neuroprotection of Sch B was investigated both in vitro and in vivo.. Sch B pretreatment ameliorated 6-OHDA-induced changes in vitro, like upregulated miR-34a expression, inhibited Nrf2 pathways and decreased cell survival, and PD feathers in vivo. Moreover, Nrf2 was negatively regulated by miR-34a, while miR-34a overexpression inhibited the neuroprotection of Sch B in both dopaminergic SH-SY5Y cells and PD mice.. Sch B showed neuroprotective effect in 6-OHDA-induced PD pathogenesis, which could be inhibited by miR-34a, involving the negative regulatory mechanism of miR-34a on Nrf2 pathways.

Topics: 3' Untranslated Regions; Animals; Behavior, Animal; Binding Sites; Brain; Cell Line, Tumor; Cell Survival; Cyclooctanes; Disease Models, Animal; Humans; Lignans; Male; Mice, Inbred C57BL; MicroRNAs; Motor Activity; Neurons; Neuroprotective Agents; NF-E2-Related Factor 2; Oxidopamine; Parkinsonian Disorders; Polycyclic Compounds; Signal Transduction; Transfection

Parkinson's disease (PD) is one of the most common neurodegenerative disorders. The aim of the present study was to investigate the protective and restorative potential of magnolol, a major bioactive biphenolic from the bark of Magnolia officinalis, for alleviating the motor deficits induced by 6-hydroxydopamine (6-OHDA) in a mouse model of PD. Before or after unilateral striatal 6-OHDA lesion induction, mice were administered magnolol subchronically; then the apomorphine-induced rotational behaviors of the hemiparkinsonian mice and tyrosine hydroxylase (TH) expression in striatum were determined. Magnolol that was administered 30 min before 6-OHDA lesion induction and then applied daily for 14 days significantly ameliorated apomorphine-induced contralateral rotation in 6-OHDA-lesioned mice, and consistently protected the decreased levels of TH protein expression in striatum. One week after termination of the 7-day subchronic pretreatment, magnolol also remarkably prevented the dopaminergic neuronal loss as identified by TH immunohistochemistry staining in striatum, associated with rotational behavioral protection in 6-OHDA-lesioned mice. Importantly, daily subchronic posttreatment with magnolol for 14 days efficiently reduced apomorphine-induced rotation, but did not restore the neuronal impairment in striatum damaged by 6-OHDA. Taken together, these findings suggest that magnolol may possess neuronal protective activity and behavioral restoration against 6-OHDA-induced toxicity in the PD model.

Topics: Animals; Biphenyl Compounds; Corpus Striatum; Disease Models, Animal; Drug Administration Schedule; Lignans; Male; Mice; Neuroprotective Agents; Oxidopamine; Parkinsonian Disorders; Tyrosine 3-Monooxygenase

The aim of this study was to determine whether sesamin, a component from Acanthopanax senticosus HARMS (ASH) pharmacologically offers protection against Parkinson's disease (PD) and its related depressive behavior in rats administered rotenone. We also examined how sesamin affected the rotenone-induced loss of tyrosine hydroxylase (TH) or glial cell line-derived neurotrophic factor (GDNF)-positive neurons in the midbrain of rats. Rats were orally administered sesamin (3, 30 mg/kg) once a day for 2 weeks before an intraperitoneal injection of rotenone (2.5 mg/kg). The pole test and catalepsy test were used to evaluate the effects of sesamin administration on bradykinesia and depressive behaviors in the PD model of rats given rotenone for 5 weeks. Those effects were compared with the ASH administrated group (250 mg/kg). Treatment with sesamin for seven weeks resulted in prophylactic effects on rotenone-induced parkinsonian bradykinesia and catalepsy, and the effects were equivalent to ASH effects. Immunohistochemistical analysis using TH or GDNF antibody showed that sesamin provided cytoprotective effects against rotenone-induced loss of DA cells. The results suggest that it may be possible to use the ASH and sesamin for the prevention of nigral degenerative disorders, e.g., PD with depression, caused by exposure to pesticide or environmental neurotoxins in general.

Topics: Animals; Depressive Disorder; Dioxoles; Eleutherococcus; Lignans; Male; Parkinsonian Disorders; Plant Bark; Plant Extracts; Rats; Rats, Inbred Lew; Rotenone