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Thesis Summary



TITLE:

          Studies on Parkinson's Disease: Search for Therapeutic Agents From Herbs
and Herbal Drugs



Subject : Toxicology
Name of the student : Muzamil Ahmad.sama_4j@yahoo.co.in.
Department : Centre for Biotechnology,
  Faculty of Science
Name of the supervisor : Dr Fakhrul Islam.fislam2003@yahoo.co.in.
Co- supervisor
: Dr. Saleem Javed
Date of Viva Voce : 30th August 2003


Summary

         Parkinson’s disease (PD) is an age-related disorder, more common in senior citizens than in younger ones. The disease is accompanied by the symptoms like rest, tremor, bradykinesia, rigidity, stooped posture and instability. The proper cause of this disease still remains a mystery, despite the role of oxidative stress, free radical formation, genetic susceptibility, programmed cell death and some unknown factor, which may be endogenous or exogenous. The disease progresses slowly and may ultimately produce complete akinesia. The neuropathology of the disease is based on the depigmentation and cell loss in the dopaminergic nigrostriatal tract of the brain with the corresponding decrease in the striatal dopamine concentration and the presence of eosinophilic inclusions called Lewy bodies.

         Current pharmacological therapies for the disease are inadequate; these are only able to provide symptomatic relief and after long use produce stern side effects and even worsen the condition.

         Herbal medicines are being used since antiquity in folklore and indigenous systems of medicine to treat disease from mild headache to dreaded cancer. They are preferred choice because of their easy accessibility and the notion that they are safer than synthetic drugs, which however, may not be always true. The safety of herbal drugs is only relative but the population feels more assured because of their long and wide spread usage and their familiarity with the plants. Knowledge from the use of medicinal herbs and their active ingredients serve as the foundation for much of the modern pharmacology. In recent times herbal medicines are gaining priority in developed pharmaceutical market because of availability, safety and no major regulatory controls. This study was an attempt towards search for effective and safe alternatives from herbs to protect PD.

         Three herbal drugs Ginkgo biloba, Nardostachys jatamansi and Withania somnifera were studied for anti-parkinsonian effects in Wistar rats. These herbs were selected after a extensive survey of the literature for the purpose and advice from the practicing physicians of Unani and Ayurvedic systems of medicine. There are ample reports in the literature for these plants to be used in various neuro-disorders in clinical and experimental studies, beside their use in folklore against various health conditions. The parameters of study included: (a) Behavioural studies (b) Biochemical/enzymatic estimations (c) Dopaminergic D2 receptor binding assays (d) Catecholamine quantifications and (e) Immunohistochemical studies.

         Parkinsonism was induced in the rats by injecting 6-OHDA into the right striatum stereotactically. Lesioning with 6-OHDA resulted in significant enhancement of lipid peroxidation (LPO) and reduction in the content of glutathione (GSH) and reduced activities of its dependent enzyme system (i.e. glutathione-s-transferase, glutathione reductase and glutathione peroxidase) along with that of superoxide dismutase and catalase. There had also been a marked up regulation of Dopamine D2 receptor binding and a decrease in the content of dopamine and its metabolites (dihydroxyphenyl acetic acid and homovalinic acid). All the changes were further emphasized by the reduced expression of tyrosine hydroxylase, a marker enzyme for PD, in the ipsilateral striatum of lesioned rats as confirmed by immunohistochemistry. Pre-treatment with test drugs for three weeks, prior to lesioning, markedly reversed all the behavioural, biochemical, neurochemical and immunohistochemical changes.

         It is premature to propose the mechanism(s) involved in the observed anti-parkinsonian effects of the herbal drugs studied, and at the same time we do not consider that these effects were elicited through a single mechanism. On the basis of present findings and reported properties of test drugs, it is proposed that these agents improve overall physical and mental performance through antioxidant, anti-stress, immunomodulatory and adaptogenic effects; furthermore, animal model used for the disease do not simulate the precise clinical event as most of the behavioural deficits can never be observed in animal models, but are still relevant for elucidating the mechanisms and testing the efficacy of various therapeutic agents. In spite of these limitations, we consider the findings to be very encouraging with good anti-parkinsonian potential and advocate that these plants for further investigations. Undoubtedly elucidation of proper molecular mechanisms and deciphering appropriate genetic pathways can go a long way in emphasizing our studies.