Protective effects of oxyresveratrol on motor functions in 6-OHDA-induced neurodegeneration

Abstract

Parkinson disease (PD) is the second most common neurodegenerative disorder, associated with progressive loss of dopaminergic neurons in the substantia nigra. Majority of PD is due to environmental factors. PD affects approximately 1% of the population over age 55, and 2% of the population over age 65 worldwide and this number is increasing. One of the most typical symptoms of PD is a motor deficit. Parkinsonian mimetic 6-hydroxydopamine (6-OHDA) can be served as a toxin agent in an experimental model for PD. Oxyresveratrol (OXY) is a stilbene extracted from mulberry. OXY has been shown to exert anti-oxidative effects against cerebral ischemia. The aim and Objective of this study is to investigate the underlying protective effect of Oxyresveratrol in PD.

In our cell culture study, we found that 25 μM of Oxy-treated cells significant decrease LDH level in the cell medium, which we believed 25 μM of Oxy could prevent cell death. 25 μM of Oxy treated cell also significant decrease cleaved caspase 3 expressions reduce the oxidative stress level in a cell by decreasing the level of eIF2α and JNK. In of Bcl-2 to Bax ratio showed bax level was reduced as Bax servers as an apoptosis promoter.

In the animal study, male Sprague Dawley rats were fed with Oxyresveratrol (Oxy), resveratrol (RES) as a positive control and pinostilbene (PINO) as a negative control at a dose of 1 mg/kg for 7 days prior to stereotactic injection of 6-OHDA in MFB region. Rats were continued to be fed with the drug for 14 days after surgery. In the cylinder and rotarod test, and apomorphine-induced rotation test, 6-OHDA-lesioned plus Oxy-treated group showed significantly improved the balance on rotarod by decrease the latency to fall and significantly reduce the number of turn in apomorphine-induced rotation test. 6-OHDA-lesioned plus Oxy treated group significant increase TH level in Substantia Nigra Pars Compacta (SNpc) compared to the 6-OHDA-lesioned group, also significant decrease cleaved caspase 3 expressions and the level of eIF2α and JNK. All those significant results are encouraging, and we believed that Oxy is potential products to help Parkinson patient to prevent loss of dopaminergic neurons.