Isorhynchophylline ameliorates MPTP-induced motor impairment and MPP+-induced cytotoxicity in experimental Parkinson’s disease models
Refereed conference paper presented and published in conference proceedings


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AbstractBackground and Aims:
Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor dysfunction, progressive accumulation of aberrant alpha-synuclein (α-syn) and the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc).
Isorhynchophylline (IRN), an oxindole alkaloid, has been identified as the main active ingredient responsible for the biological activities of Uncaria rhynchophylla. IRN was shown in previous studies to exert neuroprotection in various models of neurological diseases. Based on these findings, we hypothesized that IRN may be a potential antiPD agent. This study aims to explore the actions and underlying mechanism of IRN in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model and 1-methyl-4-phenylpyridinium (MPP+) PC12 cell model of PD.
Methods:
1. To investigate the ameliorative effect of IRN in vivo, MPTP-treated mouse model was selected in our study, which is one of the most widely applied models for PD research. Briefly, adult male BALB/c mice were injected intraperitoneally with MPTP (25 mg/kg) once per day for seven consecutive days to induce subacute PD model, IRN (20 and 40mg/kg) was given intragastrically respectively 2 h before MPTP injection. Following the drug treatment, behavior tests were performed, including open field test, forced swim test and pole test. After behaviour tests, animals were sacrificed, and brain tissues were collected for further mechanism study.
2. To investigate the protective effect of IRN in vitro, MPP+ -treated PC12 cell model was used. Briefly, PC12 cells were maintained in DMEM supplemented with penicillin (100 U/ml), streptomycin (100 μg/ml), 6% FBS, and 6% horse serum at 37oC in a humidified atmosphere of 95% air and 5% CO2. The cells were seeded onto 96-well culture plate at a density of 2×104 cells/well and stabilized for 48 h and subsequently cultured in free serum medium and incubated with different concentrations of IRN (final concentrations: 5, 10, 20 and 40 uM) for 2 h. MPP+ at a final concentration of 500 uM was then added to the culture for an additional 24 h. Cell viability was evaluated after drug treatment by MTT assay.
Results:
Results of behavior tests showed that MPTP treatment significantly decreased the number of line crossings and rearings in open field test, caused a significant reduction of immobility time in forced swim test and slower movement in pole test comparing with those of normal control group. However, mice in MPTP+IRN (20, 40 mg/kg) treated group showed much better performance comparing with those of MPTP treated group. Which indicated that IRN significantly improved the movement deficits. In vitro findings showed that IRN (40 uM) pre-treatment increased PC12 cell viability and the length of neurite outgrowth.
Conclusions:
IRN could ameliorate the motor impairment induced by MPTP in mice and protect PC12 cell against cytotoxicity induced by MPP+. Findings of these preliminary studies indicate that IRN might be a promising therapeutic agent for PD worthy of further study on its action mechanism.
All Author(s) ListZhizhun Mo, Yan-Fang Xian, Zhi-Xiu Lin, Paul Siu-Po Ip
Name of ConferenceInternational Conference on Brain Research in Chinese Medicine: Degeneration and Repair
Start Date of Conference26/07/2018
End Date of Conference28/07/2018
Place of ConferenceHong Kong
Country/Region of ConferenceHong Kong
Proceedings TitleInternational Conference on Brain Research in Chinese Medicine: Degeneration and Repair
Year2018
Month7
LanguagesEnglish-United Kingdom

Last updated on 2019-24-10 at 14:23