Ameliorative effect of Betulinic acid on ageing and scopolamine-induced learning and memory impairment in rats

Abstract

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. In the present Objectives: study, the effect of betulinic acid was evaluated on learning and memory in aged rats as well as scopolamine-induced amnesic rats. Betulinic acid (25 and 50 mg/kg; p.o.) was administered to separate groups of Material and methods: 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. Betulinic acid significantly improved learning and Results: memory of aged as well as scopolamine-induced amnesic rats. Further, betulinic acid significantly reduced oxidativenitrosative 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 acidtreated 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 antiacetylcholinesterase activity and anti-oxidant activity. Further, the current findings support the usefulness of betulinic acid in the management of age-related cognitive dysfunction.

Phytochemicals of Minthostachys diffusa Epling and Their Health-Promoting Bioactivities

“…It has been demonstrated that betulinic acid also improves learning and memory of aged as well as scopolamine-induced amnesic rats. Furthermore, betulinic acid also decreased lipid peroxidation and nitrite level, and increased the levels of reduced glutathione and superoxide dismutase [40]. Ursolic acid isolated from Micromeria cilicica has been shown to inhibit AChE and BChE at IC 50 of 93.80 and 41.10 µM, respectively [41].…”

“…Terpenoids are reported as potential leads for the development of cholinesterase inhibitors [39][40][41]. For this reason, in vitro cholinesterase inhibition assays were also performed on the commercially available triterpenes betulinic, corosolic, maslinic, oleanolic and ursolic acids that were found in M. diffusa, in order to compare the activities of sample fractions containing these triterpenes.…”

“…Triterpenoids, such as betulinic, corosolic, maslinic, oleanolic, and ursolic acids have been shown to have several biological activities including anticancer, cytotoxic, antitumor, antioxidant, anti-inflammatory, anti-HIV, anti-cholinesterase, α-glucosidase inhibition, antimicrobial, and hepatoprotective activities [37][38][39][40]. It has been demonstrated that betulinic acid also improves learning and memory of aged as well as scopolamine-induced amnesic rats.…”

“…glutathione and superoxide dismutase [40]. Ursolic acid isolated from Micromeria cilicica has been shown to inhibit AChE and BChE at IC50 of 93.80 and 41.10 μM, respectively [41].…”