Kalaiyarasi, C (2015) Evaluation of Central Nervous System Activities of some Indian Medicinal Plants. Doctoral thesis, The Tamilnadu Dr. M.G.R. Medical University, Chennai.
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Abstract
Anxiety, epilepsy and depression are co-morbid conditions with interlinking etiology requiring chronic drugs treatment. The problems associated with available current therapy with synthetic chemicals are poor response, remission and severe undesirable side effects. Hence, the search for novel drug continues and medicinal plant source became important source for new drug development for these CNS ailments. Cassia fistula L. and Cassia auriculata L have been selected based on their traditional use and their rich flavonoid content nature as flavonoids were reported to have potential CNS effects. Preliminary phytochemical analysis showed the presence of flavonoids, terpenoids, tannins, carbohydrate and proteins in various solvent fractions of Cassia fistula L. pods and Cassia auriculata L. pods. In the quantitative estimation of phytoconstituents, ethyl acetate fraction of C. fistula (EAFCF) and n-hexane fraction of C. auriculata (NHFCA) showed to contain more polyphenols and flavonoids. HPTLC studies also carried out to confirm the presence of flavonoids in above said fractions. A flavonoid from EAFCF was isolated through column chromatography and further subjected to NMR, FT-IR and mass analysis. Results of In vitro antioxidant studies showed that EAFCF and NHFCA possessed high antioxidant property than the other fractions as both the fractions showed free radical scavenging activity and reducing power ability similar to that of the standards used. The flavonoid rich EAFCF was subjected to column chromatography and fractions were obtained. The fractions obtained from the column chromatography study were subjected to HPTLC finger print analysis. The fractions which shows single band in the HPTLC finger print analysis were taken for HPLC study. In the HPLC study a single peak was obtained at 6 minutes, was collected at the column outlet. Fractions collected from the HPLC outlet were evaporated to remove the organic solvent and aqueous phase was freeze dried and a dirty white powder was obtained. The isolated compound was subjected to various characteristic analyses like IR, MASS and NMR. The chemical structure of the isolated compound was elucidated and identified. The isolated compound was a flavonoid having a molecular weight of 290 and the compound was identified as 2-(3,4-dihydroxyphenyl) chroman-3,5,7-triol. In acute oral toxicity studies, conducted as per OECD (guideline 420) showed no mortality or toxicity up to the dose of 2000 mg/kg observed for 24 hours period. Doses for the pharmacological evaluation were fixed based on the results of acute toxicity studies. Evaluation of anticonvulsant activity of EAFCF and NHFCA was carried out in s.c. PTZ and PTZ kindling models. Both the fractions exhibited significant anticonvulsant activity as evidenced from increase in the time latency for MCS and GTCS in s.c.PTZ model and significant decrease in seizure score in EAFCF treated animals PTZ kindling model. EAFCF and NHFCA were evaluated for anxiolytic activity in EPM, OFT and in marble burying behavior models. A significant increase in open arm entries and time spent in open arm by the animals received EAFCF and NHFCA have been noted in EPM, while decrease in number of marbles buried and thigmotaxis in OFT also were noted indicating the anxiolytic activity of the fractions. Initially, both EAFCF and NHFCA were evaluated for their antidepressant activity in FST, TST models. A significant decrease in duration of immobility was exhibited by the animals treated with the fractions compared to control animals was observed in both FST and TST which shows the antidepressant potential of fractions on acute treatment. However, the clinical scenario is such that the symptoms of depression can be minimized only after three weeks of drugs treatment. Hence, the present study later evaluated antidepressant activity of the EAFCF in CUS induced anhedonia model. In this, the model group, received only the stressors exhibited depression like behavior as shown by the decrease in the sucrose consumption, increase in the duration of immobility and decrease in erythrocyte SOD activity. Above parameters were reversed by the treatment of fractions indicating the antidepressant potential after chronic treatment. Most of the currently used antiepiletics and antidepressants are also used for alleviating pain as they possess analgesic and anti-nociceptive abilities. Therefore, in the present study, both EAFCF and NHFCF were screened for analgesic and antinociceptive activities in acetic acid induced writhing, tail flick, hot plate and formalin tests. Acetic acid induced writhing model is employed for screening peripheral analgesics and both the fractions significantly reduced the acetic acid induced writhing indicating the peripheral analgesic potentials probably through blockade of release of pain mediators. In hot plate and tail flick models, latency of response to pain stimuli was increased significantly in EAFCF and NHFCA treated animals demonstrating the anti-nociceptive potential. In addition, the fractions reduced the initial neurogenic and later inflammatory pain in formalin test as evidenced from the significant decrease in paw licking responses. Drugs showing either of anxiolytic, anticonvulsant, antidepressant or analgesic activity or combination of above activities may possess sedative property or motor toxicity as adverse effects. In the present study, EAFCF was not shown either of the adverse affects in the doses used in the present study. However, NHFCA at highest dose used in this study showed mild sedative and skeletal muscle relaxant properties (p<0.05). To find out the mechanism involved in above discussed pharmacological activities, the changes in the neurochemicals level such as GABA, glutamate, serotonin and adenosine upon the treatment EAFCF were estimated in HPTLC. Treatment of EAFCF significantly increased the levels of GABA, serotonin and adenosine while it decreased the glutamate level. Adenosine is one of the significant neuromodulater believed to modulate the release of most of the neurotransmitters. Hence, the present study further focused on the evaluation role of adenosinergic system on the CNS effects of EAFCF. A synergistic interaction of exogenous adenosine administration and its receptors agonists with EAFCF treatment was noted in EPM, FST, s.c. PTZ and formalin test. Meanwhile, adenosinegic blocking agents showed antagonistic interaction with EAFCF in the above chosen models of anxiety, seizure, depression and pain. These results indicate that the EAFCF possess anxiolytic, anticonvulsant, antidepressant and analgesic activity through modulation of adenosinergic system. In conclusion, the plants Cassia fistula and Cassia auriculata have potential anxiolytic, anticonvulsant, antidepressant and analgesic activities and adenosine may play a role in the CNS effects of Cassia fistula.
| Item Type: | Thesis (Doctoral) |
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| Uncontrolled Keywords: | Evaluation, Central Nervous System Activities, Indian Medicinal Plants. |
| Subjects: | PHARMACY > Pharmaceutical Analysis |
| Depositing User: | Subramani R |
| Date Deposited: | 20 Aug 2017 06:35 |
| Last Modified: | 28 Oct 2022 15:44 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/2731 |
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