1. Resveratrol synergizes with low doses of L-DOPA to improve MPTP-induced Parkinson disease in mice
- Author
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Yongzhe Che, Qin-Yi Yu, Pei-En Jiang, Qianqian Liu, Xizeng Feng, Dashuai Zhu, Shaozhi Zhang, Xinyu Tang, and Qiu-Han Lang
- Subjects
Antioxidant ,medicine.medical_treatment ,Nigrostriatal pathway ,Striatum ,Resveratrol ,Pharmacology ,Neuroprotection ,Antioxidants ,Antiparkinson Agents ,Levodopa ,03 medical and health sciences ,Behavioral Neuroscience ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Dopamine ,medicine ,Animals ,030304 developmental biology ,0303 health sciences ,Mice, Inbred BALB C ,business.industry ,MPTP ,Dopaminergic ,MPTP Poisoning ,Drug Synergism ,nervous system diseases ,Disease Models, Animal ,medicine.anatomical_structure ,chemistry ,Drug Therapy, Combination ,Female ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
L-DOPA (L-3,4-dihydroxyphenylalanine) relieves symptoms of Parkinson disease (PD), but long-term use can cause serious side effects. Resveratrol (3,5,4′-trihydroxy-trans-stilbene, RV), a polyphenolic compound derived from grapes and red wine that has antioxidant activity, has been shown to have neuroprotective effects. RV was investigated to enhance the therapeutic effect of L-DOPA in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse model of Parkinson disease. Mice received a saline or RV injection (10 mg/kg/day), then 2 h later, saline or MPTP (15 mg/kg/day) was administered for 7 consecutive days. Saline or L-DOPA (5 or 8 mg/kg/day) was injected post-administration of MPTP for the last 2 consecutive days. Our results indicated that RV alleviated MPTP-induced loss of dopaminergic neurons and attenuated astroglial activation in the nigrostriatal pathway. In parallel, RV reduced the expression of α-synuclein in the striatum. In addition, RV also increased levels of the anti-apoptotic signalling molecule Bcl-2, reduced levels of the pro-apoptotic signalling molecule Bax, and reduced activation of caspase-3 in the striatum. Specifically, RV significantly reduced motor dysfunction in MPTP-treated mice. Furthermore, the RV-treated group showed less IL-1β and an enhanced pAkt/Akt ratio, which promoted dopamine neuron survival in the striatum. We found that the effects of co-administration of RV with L-DOPA (5 mg/kg) were equivalent to those of administration of 8 mg/kg L-DOPA in MPTP-induced PD mice. Therefore, with fewer side effects, L-DOPA can be effectively used in the treatment of PD over a long period of time.
- Published
- 2019