Poonam Ruhal, Dinesh Dhingra*
Pharmacology Division, Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology,
Hisar -125001, Haryana (India).
*Address for Correspondence
Prof. Dinesh Dhingra, M. Pharm., PhD
Department of Pharmaceutical Sciences,
Guru Jambheshwar University of Science and Technology, Hisar -125001, Haryana, India
Background: Ageing is a natural process which includes a progressive decline in cognitive functions as a result of maladaptation of cholinergic neuronal activity. The reason behind ageing-induced cholinergic neuronal loss is largely unknown, however, oxidative stress is speculated to be majorly involved in its aetiology. Objectives: In the present study, the effect of betulinic acid was evaluated on learning and memory in aged rats as well as scopolamine-induced amnesic rats. Material and methods: Betulinic acid (25 and 50 mg/kg; p.o.) was administered to separate groups of rats for 7consecutive days. Donepezil (1 mg/kg; i.p.), an acetylcholinesterase inhibitor was used as a standard drug. Behavioral models such as Morris water maze and elevated plus maze were used to evaluate the effect of drugs on learning and memory of rats. After behavioral studies, animals were sacrificed and their brain was isolated and further processed for estimation of various biochemical parameters such as acetylcholinesterase activity, oxidative and nitrosative stress markers and histological examinations. Results: Betulinic acid significantly improved learning and memory of aged as well as scopolamine-induced amnesic rats. Further, betulinic acid significantly reduced oxidative-nitrosative stress, as indicated by decreased lipid peroxidation and nitrite level and increased the levels of reduced glutathione and superoxide dismutase, in both aged as well as scopolamine-induced amnesic rats. Further, the AChEs activity was found to be significantly reduced after administration of high dose (50 mg/kg) of betulinic acid in aged rats as well as scopolamine-induced amnesic rats. In addition, histopathological evaluation showed that betulinic acid-treated aged rats have less number of pyknotic neurons in hippocampal CA1 region as compared to aged control rats. Conclusion: The present study provides the pharmacological evidence for neuroprotective and memory enhancing effect of betulinic acid in aged as well as scopolamine-induced amnesic rats, possibly through its anti-acetylcholinesterase activity and anti-oxidant activity. Further, the current findings support the usefulness of betulinic acid in the management of age-related cognitive dysfunction.
Keywords: Acetylcholinesterase, ageing; betulinic acid; dementia; learning; memory