Study of Novel Scaffolds from Natural Product for the Treatment of Neurodegenerative Diseases

Abstract

Neurodegenerative disease is a term applied to a variety of conditions which result from a chronic breakdown and deterioration of neurons, particularly, those of central nervous system. Alzheimer’s disease, Huntington disease and Parkinson’s disease are associated with neurodegenerative diseases due to involvement of similar molecular mechanisms such as neuroinflammation, excitotoxicity, mitochondrial dysfunction and oxidative stress. Ficus racemosa, Ficus religiosa and Corchorus trilocularis are supposed to have effective neuroprotective role on oxidative stress and cognitive functions. The present study has been designed to demonstrate the neuroprotective role of novel scaffolds from pet. ether, ethyl acetate and ethanolic extract of Ficus racemosa, Ficus religiosa and Corchorus trilocularis against neurotoxin induced animal models. Colchicine was administered intracerebroventricularly to induce Alzheimer’s disease, 6 hydroxydopamine was administered intracerebroventricularly to induce Parkinson’s disease and 3 nitropropionic acid was administered intraperitoneally to induce Huntington’s disease. Pet. ether, Ethyl acetate and ethanolic extracts of Ficus racemosa, Ficus religiosa and Corchorus trilocularis were prepared by soxhaltion method and were administered (100, 200 and 400 mg/kg, p.o) on different time intervals in animals. Behavioral assessments were performed on respective days. Animals were sacrificed at the end of experiments for biochemical and histpathological estimation. This study indicated significant alteration in behavioral parameters (hypolocomotion, muscle incoordination and memory deficit), biochemical (increased lipid peroxidation, decreased catalase, superoxide dismutase and reduced glutathione), and increased neurochemical (increased acetylcholinesterase enzyme) in all neutotoxin treated animals. Higher doses of pet. ether extract of Ficus racemosa (200 and 400 mg/kg) showed maximum significant protection in the form of behavioral, biochemical and neurochemical alterations compared to other extracts of Ficus racemosa, Ficus religiosa and Corchorus trilocularis in neurotoxin treated rats. On the basis of maximum protection, different fractions have been separated by flash chromatography from pet. ether extracts of F. racemosa using n-hexane : acetone (8:2 v/v) solvent system at 210 nm. Different fractions named JOBSRA01-05 were administered (10, 20 and 40 mg/kg, p.o) on different time intervals in colchicine induced memory impairment, 6 OHDA induced Parkinson’s disease and 3 nitropropionic acid induced Huntington’s disease in animals. Behavioral assessments were performed on respective days. Animals were sacrificed at the end of experiments for biochemical and histpathological estimation. The results obtained in the pharmacological investigation of fractions suggest that the neuroprotective activity of Fractions JOBSRA01 and JOBSRA03 are more promising than other fractionsFraction JOBSRA01 (20 mg/ml) was prepared in n-hexane and applied on the plate. The composition of mobile phase was n-hexane: ethyl acetate (11:1). Chromatogram was observed in daylight, under ultra violet (UV) light at 254 and 366 nm wavelength. Flash chromatographic separation of Fraction JOBSRA01 resulted in isolation of two constituents JOBFRA01 and JOBFRA02. Dried components were subjected for the confirmation and structural elucidation by HPTLC, IR, NMR and Mass spectroscopy. The proposed structure assigned to isolated constituent on the basis of IR, NMR and Mass data is identical to that of known compound JOBFRA01 Gluanol acetate and JOBFRA02 β-sitosterol. From the above results, it is concluded that the neuroprotective activity was due to the effect of Fraction JOBSRA01 of petroleum ether extract of Ficus racemosa fruits in different animal models of neurodegenerative diseases. However, it needs screening of the above mentioned active principle/s in Fraction JOBSRA01 to pin point the pharmacological screening of drug.