Neuroprotective Effects of Ellagic Acid in a Rat Model of Parkinson's Disease.

Antioxidants have protective effects against free radicals-induced neural damage in Parkinson's disease (PD). We examined the effects of ellagic acid (EA) on locomotion, pallidal local EEG, and its frequency bands' power and also cerebral antioxidant contents in a rat model of PD induced by 6-hydroxidopamine (6-OHDA). 6-OHDA (16 µg/2µ l) was injected into the right medial forebrain bundle (MFB) in MFB-lesioned rat's brain. Sham group received vehicle instead of 6-OHDA. PD-model was confirmed by rotational test using apomorphine injection. EA (50 mg/kg/2 ml, by gavages) was administered in PD+EA group. One group of MFB-lesioned rats received pramipexole (PPX; 2 mg/kg/2 ml, by gavages) as a positive control group (PD+PPX group). Motor activity was assessed by stride length, rotarod, and cylinder tests. Pallidal local EEG was recorded in freely moving rats. The levels of malondialdehyde (MDA) besides Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were measured in both striatum and hippocampus tissues. MFB lesion caused significant reduction of stride-length (P<0.001), bar decent latency (P<0.001) and frequency bands' power of pallidal EEG (P<0.001). Use of 6-OHDA caused a reduction in the GPx (P<0.001) and SOD (P<0.001) activities while increased significantly the levels of MDA (P<0.001) in MFB-lesioned rats. EA significantly restored all above parameters. The results show that EA can improve the motor impairments and electrophysiological performance in the MFB-lesioned rats via raising the cerebral antioxidant contents. Therefore, EA can protect the brain against free radicals-induced neural damage and may be beneficial in the treatment of PD.

Ellagic acid improves hyperalgesia and cognitive deficiency in 6-hydroxidopamine induced rat model of Parkinson's disease.

OBJECTIVES: Parkinson's disease (PD) is known for motor impairments. But often, there are non-motor symptoms such as cognitive deficiency and pain misperception, owing to possible role of nigrostriatal pathway. Antioxidants have protective effect on free radical-induced neuronal damage in PD. To further address, we examined the effects of ellagic acid (EA) in a rat model of PD induced by 6-hydroxidopamine (6-OHDA). MATERIALS AND METHODS: Right medial forebrain bundle (MFB) was lesioned by injecting 6-OHDA (16 µg/2 µl), in PD-animals. Sham operated animals received vehicle instead of 6-OHDA. PD was approved by apomorphine-induced contralateral rotation. EA (50 mg/kg/2 ml, PO, for 10 days) was administered to PD-EA group. Some PD-animals received pramipexole (PPX; 2 mg/kg/2 ml, PO) as a positive control group. Analgesia was measured by tail-flick and hot-plate tests. Passive avoidance task was measured by shuttle box apparatus to record the initial and step-through latency. Spatial cognition task was evaluated by Morris water maze test, measuring the escape latency time, path length, swimming speed and time spent in target quadrant. RESULTS: MFB-lesioned rats showed hyperalgesic responses to the stimulus in tail-flick and hot-plate tests. Also they showed memory and learning deficit in cognitive tests. These effects reversed by EA treatment. CONCLUSION: 6-OHDA can induce oxidative stress and can disrupt the neural mechanisms underlying proper integration of painful stimuli and cognitive processes in MFB-lesioned rats. Consequently, nigrostriatal pathway can play possible role in nociception and cognition. EA, a natural antioxidant, has neuroprotective effect on this pathway and can ameliorate this defect and be considered in PD management.