Arun Prasanth, S (2021) Evaluation of Huntington Effect of Ethanolic Extract of Pedalium Murex Linn Leaf in 3-Nitropropionic Acid Induced Neurodegeneration. Masters thesis, Annai J.K.K. Sampoorani Ammal College of Pharmacy, Komarapalayam.
Full text not available from this repository.Abstract
The 3-NPA mimics a downstream process of cell death seen in selective excitotoxic striatal pathology in the Huntington’s disease (HD) where it inhibits the mitochondrial enzyme succinate dehydrogenase. It was found that intoxication with 3NPA causes Ca2+-induced mitochondrial permeability transition. 3NPA may, therefore, be used as an experimental animal model of HD. EFFECT OF EEPML ON IN VITRO ACHE ENZYME ACTIVITY: The critical role of cholinesterases in neural transmission makes them a key target of a large number of cholinesterase-inhibiting drugs relevant to the treatment of neurodegenerative disorders [16].To evaluate the potential of the EEPML as an anti-Huntington drug, its AChE inhibitory activity was quantified. As shown in Table 2, the EEPML showed significant AChE inhibitory effect (p < 0.05) ( Fig No.6) when compared to the standard (Donezepil hydrochloride) and the cholinesterase inhibitory activity occurred in a dose-dependent manner. ANTI-OXIDANT EFFECT OF EEPML: Reactive oxygen spieces (ROS,) attack DNA and causes mutation leading to pathological conditions such as neurodegeneration, ageing process and dementia. For the treatment of diseases caused by ROS, antioxidant is used. Phenolic compounds such as flavonoids have been shown to possess significant antioxidant activity. The phenolic compounds in herbs acts as antioxidants due to their redox properties, allowing them to act as reducing agents, hydrogen donors, free radicals, quenchers and metal chelators. Both EEPML and Ascorbic acid produced a dose depend increase in DPPH Free radical scavenging effect. EEPML has shown 67.28±0.22% inhibition at 100 μg/ml while Ascorbic acid has shown 63.61±0.25% inhibition at 100 μg/ml. (Table No.3). The presence of phenolic compounds (containing phenolic hydroxyls) might be responsible for high antiradical properties of EEPML. Other compound flavonoids include flavones, flavanols and condensed tannins are secondary metabolites and it has antioxidant activity by the existence of free OH groups, particularly 3-OH for the prevention of oxidative stress which may responsible for DPPH activities. EFFECT OF EEPML ON BODY WEIGHT: Our finding that EEPML 200mg and 400mg treated group animals have shown significant decrease in body weight when compared with disease group animals at the end of week 1 (P<0.001) and week 2 (P<0.001)is coinciding with the finding of Mukundh N et al 2008 that administration of Ethanolic extract of Pedalium murex fruits produced significant reduction in the body weight of the hypercholesterolemia induced animals[19]. Donezepil hydrochloride treated group animals have not shown significant decrease in body weight when compared with disease group animals at the end of week 1 and week 2 (Fig No.1). EFFECT OF EEPML ON MOTOR COORDINATION: Preliminary phytochemical screening of EEPML revealed the presence of flavonoids, glycosides, tannins, carbohydrates, phenolic compounds, triterpenoids and saponins. The open-field test (OFT) has been used widely to assess emotionality and locomotor performance. OFT was used to exclude these false effects that could be associated with hyperkinesia. In our study, administration of EEPML increased the locomotor activity indicating that the specific actions of EEPML on the behavioural model are predictive of anti-immobility activity. Rotarod is widely used screening method for evaluating the locomotor activity (due to change in muscle relaxation) in rodents. It has been well-known that an augment in the concentration of gamma-aminobutyric acid (GABA) may lead to CNS depressant effect. Increase in locomotion implies that EEPML may act via GABA receptors. The observed effect on muscle (increase in fall-off time) of EEPML may be due to the antagonistic effect on GABA/benzodiazepine receptor complex. EEPML alleviates anxiety in Rotarod and open field test, the studied antioxidant pretreatments were effective in reducing 3-Nitropropionic acid-induced brain oxidative stress as evidenced by quenching of free radicals and elevation of the antioxidant SOD (Fig No.7). The behavioural effects were significantly attenuated by EEPML in a dose dependent manner. All treatments elicited significant protection but EEPML 400 mg/kg produced the best results. CONCLUSION: In our findings, EEPML showed significant results in in vitro acetylcholinesterase inhibition and in vitro free radical scavenging activity prompted us to select the ethanol extract for pharmacological screening. In this study, results of behavioural tests for motor coordination, agitated levels of acetylcholine level and SOD indicated that the 3-NPA lead to memory and learning problem and movement abnormalities in rats, which were found to be reversed by EEPML when compared to Donezepil hydrochloride treated groups. These results indicated that EEPML may be a potential candidate for 3-NPAinduced brain damage which may be attributed to the presence of potent antioxidants in EEPML. However, further extensive research is necessary to identify the exact constituents and elucidation of its possible mechanism of action underlying the anti-huntington effect of EEPML. Such new findings may be included as strategies for more effective neuroprotection in addition to current therapies.
| Item Type: | Thesis (Masters) |
|---|---|
| Additional Information: | 261925701 |
| Uncontrolled Keywords: | Evaluation, Huntington Effect, Ethanolic Extract, Pedalium Murex Linn Leaf, 3-Nitropropionic Acid Induced Neurodegeneration. |
| Subjects: | PHARMACY > Pharmacology |
| Depositing User: | Ramakrishnan J |
| Date Deposited: | 04 Dec 2021 06:15 |
| Last Modified: | 28 Aug 2022 07:47 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/18857 |
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