Isolation, characterization of ursolic acid & its synthetic modification as new neuro-protective agent for prevention of cognition defects and oxidative damage

Objective: This present study was targeted to explore potential of ursolic acid and attempts were made to derivatize the compound to see its potential as new neuro-protective agent for prevention of cognition defects & oxidative damage in the treatment of cognitive disorders such as dementia and Alzheimer’s disease.Methods: Acetone extract of Eucalyptus hybrid was subjected to column chromatography and fraction containing Ursolic acid was determined. Ursolic acid was further synthetically derivatized to C2-C6. Compounds C2-C4 were prepared by treating ursolic acid with different acid chlorides, C5 was prepared by treatment of ursolic acid with methyl iodide, C6 was prepared by treatment of compound C2 with oxalyl chloride to form C2a then treated with propyl amine to form C6. Structures were confirmed by spectroscopy of synthesized compounds. These compounds were screened to assess their neuro-protective potential on mouse model of D-galactose (150 mg/kg) induced neurotoxicity.Results: Pre-treatment of C1-C6 (10 mg/kg) each for successive 14 days significantly attenuated the neuro-toxic effect of D-galactose (150 mg/kg) (p <0.05). Ursolic acid and synthesised derivatives significantly decreased escape latencies as compared to D-galactose treated groups using Morris water maze. There was significant improvement in lipid per-oxidation and reduced glutathione levels in groups treated with standard Donepezil as well as in groups treated with Ursolic acid and its derivatives. Moreover, significant improvement was observed in C2 and C6 groups suggesting the best antioxidant activity.Conclusions: The results of the present study suggest that C2 and C6 exhibit significant Neuro-protective activity in D-galactose induced neuro-toxicity in rats. Hence C2 and C6 could be beneficial in the treatment of cognitive disorders such as dementia and Alzheimer’s disease.