In this study we selected a rat model of Parkinson's disease (PD) by using intrastriatal infusion of the 1-methyl-4-phenyl-pyridinium ion (MPP+) to investigate the neuroprotective action of melatonin and its inhibitory activity on MPP+-impaired glutathione (GSH) system in the nigrostriatal system. Results show that MPP+ caused not only a severe neuronal injury in the striatum and in the ipsilateral substantia nigra (SN), but it also induced a significant decrease in GSH levels and an increase in the GSSG/GSH ratio 3 days after intrastriatal MPP+ infusion. Intraperitoneal co-administration of melatonin (10 mg/kg, five times) significantly attenuated MPP+-induced nigrostriatal neurotoxicity and GSH impairment. Depletion of cytosolic GSH by L-buthionine sulfoximine (BSO) did not cause neuronal damage by itself. It, however, when co-administrated with MPP+, potentiated the GSH reduction in the striatum, without aggravating nigrostriatal neurodegeneration induced by MPP+. Moreover, the MPP+-caused neuronal damage was positively correlated with a rising ratio of GSSG/GSH, but not with a drop of GSH. These results suggest that the MPP+-triggered oxidative stress may play a more important role than the loss of the antioxidant GSH in determining neuronal injury. Interestingly, the neuronal damage and oxidative stress elicited by co-treatment of BSO with MPP+ were effectively reduced by melatonin. Our results hence provide direct evidence showing that melatonin attenuates MPP+-induced nigrostriatal dopaminergic injury by its ability to impede the increase of GSSG/GSH ratio; therefore melatonin may have therapeutic implications in PD.

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Accumulating evidences have proved the protective role of traditional Chinese medicine in improving neurological damage induced by cerebral hypoxia‐ischemia. Herein, we hypothesized that Dendrobium officinale aqueous extract exerted neuroprotection against brain damage. Initially, a model of hypoxic‐ischemic brain damage (HIBD) was induced in neonatal rats, which were subsequently intragastrically administered with different doses of Dendrobium officinale aqueous extract. Next, the antioxidant capacity was examined by enzyme‐linked immunosorbent assay. 2,3,5‐Triphenyltetrazolium chloride and terminal deoxynucleotidyl transferase‐mediated dUTP nick end‐labeling staining assays were adopted to determine neuronal apoptosis in brain tissues. Furthermore, neurotrophic factors and hypoxia‐inducible factor‐1α (HIF‐1α) expression was identified by Western blot analysis. The neonatal rat models of HIBD presented impaired neurobehaviors and antioxidant capacity, increased neuronal apoptosis and expression of HIF‐1α and histone deacetylase 1 (HDAC1), as well as diminished expression of neurotrophic factors and K+‐Cl−‐cotransporter 2 (KCC2). Notably, in response to different doses of Dendrobium officinale aqueous extract, the impairment on neurobehaviors and antioxidant capacity was alleviated, accompanied by reduced levels of nitric oxide synthase, nitric oxide, and malondialdehyde, and increased superoxide dismutase activity. Besides, the neuronal apoptosis was inhibited as reflected by down‐regulated cleaved caspase‐3 and Bax and up‐regulated Bcl‐2. Moreover, we also found accelerated expression of neurotrophic factors and KCC2 and diminished expression of HIF‐1α and HDAC1. Altogether, this present study highlights that the aqueous extract of Dendrobium officinale can suppress the neuronal apoptosis and enhance the expression of neurotrophic factors to protect neonatal rats against HIBD.

α-Synuclein (α-Syn) plays a key role in the development of Parkinson' desease (PD). As aging is acknowledged to be the greatest risk factor for PD, here we investigated α-Syn expression in the ileum, thoracic spinal cord, and midbrain of young (1-month-old), middle-aged (6-, 12-month-old) to old (18month-old) mice. We demonstrated that both the levels of α-Syn monomers, oligomers and ratios of oligomers to monomers were increased with aging in the ileum, thoracic spinal cord, and midbrain.Whereas, the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme for dopamine synthesis, was decreased with aging in the midbrain. We failed to nd corresponding α-Syn mRNA increase with aging. However, we found an increased expression of caspase-1 in the ileum, thoracic spinal cord, and midbrain. A speci c caspase-1 inhibitor VX765 signi cantly reduced levels of both the α-Syn monomers and oligomers triggered by the rotenone in vitro. Taken together, the increase in α-Syn aggregation with aging might not occur rst in the gut, but simultaneously in the nervous system of gut-brain axis.. The mechanism of the age-dependent aggregation of α-Syn in nervous system is likely triggered by the agingrelated caspase-1 activation.