Amerelioating Effect of Aloe Vera in Neurotoxin Induced Parkinsonian Disease: Behavioral Assessment with Tardive Dyskinesia Test in Albino Mice

Till today, plants serve as exemplary source of medicine to treat many ailments over the years1. Aloe vera (Family: Liliaceae), plant extracts have shown demonstrable medicinal uses.2 It has demonstrated better improvement in lipid profile status among rats with streptozotocin-induced diabetes3. It has shown improvement in immunomodulation, inflammatory pain modalities. Such report suggests that A.vera might have some beneficial effects in the treatment of some central nervous system diseases. The clinical syndrome of Parkinsons disease results from neuronal degeneration of the dopaminergic cells in the pars compacta. It is proposed that neuronal degeneration is due to oxidative stress.4 Because of the more untoward side effects related to the present pharmacotherapy of parkinsons disease, the usage of natural medicinal products are looked for the better alternatives. Thus, strategies employing antioxidant and neuroprotective from natural medicinal plant extracts can yield us thebetter outcome for the treatment of Parkinson‘s disease. Vacuous chewing movements in rats are widely accepted as an animal model of tardive dyskinesia.5 Previous studies undertaken by us shows that A.vera 6 possess antioxidative properties and showed beneficial effect in parkinson disease animal model Idifferent assessment paradigms. The present study was undertaken in order to further strengthen the evidence of protective role of A.vera in MPTP induced parkinsonism using different behavioral assessment features.

In the present study, Swiss albino mice of either sex (25- 30 g), were used for the study. The study was duly approved by the Institutional Animal Ethics Committee. The study was conducted at Department

to January 2009. All the experiments were performed at daytime between 09:30 and 15:30 hours. Care of animals was according to the guidelines of Committee for the Purpose of Control and Supervision of Experiments on Animals. The animals were divided into 05 groups (n =12). Group I- was treated with distilled water (orally, once per day ×15 days). Group II- MPTP (2 doses, each dose 20 mg/kg at 2 hr. interval, i.p. daily x 15 days). Groups III, IV- A.vera (200, and 400 mg/kg/day, orally), respectively, x 15 days along with MPTP. Group V- Levodopa (30mg/kg, i.p, once per day x 15 days) along with MPTP. The A.vera (200mg/kg, 400mg/kg) orally and Levodopa (30mg/kg, i.p.) were given 30 minutes prior to MPTP administration for 15 days.

Tardive Dyskinesia infers to the Vacuous Chewing Movements (VCMs) seen in animals. If tongue protrusion, vacuous chewing movements happened along with grooming, they were not taken into consideration. The behavioral parameters of oral dyskinesia were assessed for a period of 5 min.

movements (VCMs) was seen on 7 day and on 15 day when compared to control group. Whereas, good improvement was seen in Levodopa treated group i.e. significant decrease in (VCMs) p<0.001 was seen on 7th day and on 15th day when compared to MPTP treated group. When A.vera 200mg/kg and 400mg/kg were administered, it did not cause any significant change in (VCMs) on the 7th day and on 15th day. However, on 15th day, A.vera 200mg/kg and 400mg/kg pretreated groups whereas no significant difference in (VCMs) was seen when A.vera 400 mg/kg treated group compared to levodopa treated group.

DISCUSSION:

The exact cause for the pathogenesis of the parkinsons disease is yet to be identified, but, the literature shows the vital role of oxidative stress in the causation of the disease.8 When it was compared to the different parts of the brain, it was evident that substantia nigra pars compacta was exposed to a higher rate of reactive oxygen species formation and profound margin of oxidative stress. This may be attributed to the more energy metabolism of these cells or to more content of neurotransmitter- dopamine.9 Literature also support the fact that oxidative stress changes is clearly evident in the brain of Parkinson‘s disease patients.

(MPTP), 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine is used experimentally to mimic Parkinson‘s disease model in animals. Certain aspects of the Parkinson‘s disease such as catalepsy, motor incoordination and bradykinesia can be easily studied in this model. As MPTP is highly lipophilic, makes it enable to cross the blood brain barrier immediately after its systemic absorption. Once MPTP reaches the brain tissue, it is converted to the hydrophilic metabolite 1-methyl-4 phenylpyridinium ion (MPP+), the free radical reactive specie in the causation of dopaminergic neuronal loss. It is established that these free radical reactive species play a vital role in the pathogenesis of dopaminergic neuronal loss in Parkinson‘s disease.10

A.vera is an vital medicinal plant that has proven beneficial role in oxidative stress. Numerous researches have shown that A.vera has significant anti-oxidant properties.12 It has been hypothesized that antioxidants may play neuroprotective role in

intracellular free radicals.

Previous studies have demonstrated that anti-inflammatory drugs such as acetylsalicylic acid are protective against MPTP -induced striatal dopamine depletion in mice.10

Previous studies show that Aloe vera leaf gel extract was found to have anti-inflammatory property. A.vera leaf gel has many active principles like- is anthraquinones such as aloin A and B, aloe-emodin, aloetic acid. The active principle - Aloin has shown its anti-inflammatory activity in the rat colitis, and in our study, extract of A.vera contains relatively high amount 3.14% of aloin. Further many researches are needed to elucidate whether anti-inflammatory and anti-oxidant properties of aloin are responsible for the anti-Parkinson effect or the mixture of all the components viz. barbaloin, glucomannan, acemannan, etc. are responsible for the observed beneficial effects.Lower levels of lipid peroxides in the brains of the drug-treated group and increased activities of enzymatic and non-enzymatic antioxidants in the brain suggest that the extract reduces oxidative stress in haloperidol and MPTP induced parkinsonian animal models.13 Thus further researches are welcomed to clearly establish the role of its role A.vera as an anti-parkinson agent, and benefit the mankind.

MPTP is a potent neurotoxin is commonly used to create experimental model of Parkinson‘s disease. The results of the present study conclusively demonstrated that A.vera has beneficial effects in tardive dyskinesia test. In this regard, future studies on this topic may provide an elaborate view to use A.vera in clinical medicine for treatment of Parkinson‘s disease and its neurological sequel. Conflict of interest: Declared none.

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Post-Graduate Student, Department of Industrial Biotechnology, National Institute of Technology Karnataka, Surathkal, Karnataka