Diastereomeric Mixture of Calophyllic and Isocalophyllic Acid Ameliorates Scopolamine-Induced Memory Impairment in Mice: Involvement of Antioxidant Defense and Cholinergic Systems

Dementia of Alzheimer disease type (AD) and type 2 diabetes mellitus (T2D) are two most common diseases of aging which has reached epidemic proportions. Moreover, there is a shared mechanism of pathogenesis between metabolic disorders and AD. Hence, the need for discivery of effective prevention and treatment strategies. Diastereomeric mixture of calophyllic acid and isocalophyllic acid (ISO) has been shown to stimulate glucose uptake through GLUT4- translocation. In this study, an attempt was made to investigate the effect of ISO on scopolamine-induced memory deficit in mice. ISO (5, 25 or 50 mg/kg, p.o.) or vehicle (10 ml/kg, p.o.) was administered for 3 consecutive days. One hour post-treatment on day 3, scopolamine (3 mg/kg, i.p.) was given before the animals were subjected to Y-maze, open field, novel object recognition (NOR) or Morris water maze (MWM; 5 consecutive days) paradigms. The mice were sacrificed 45 min after MWM test on day 8. The hippocampus and prefrontal cortex were rapidly isolated on ice for assay of biochemical markers of oxidative stress and acetylcholinesterase activity. Scopolamine reduced the percentage alternation behaviour in the Y-maze and discrimination index in NOR tests with no significant change in escape latency time in MWM task suggestive of deficit in learning and memory. However, the pretreatment of mice with ISO produced a dose-dependent improvement in learning and memory. Moreover, ISO administration attenuated scopolamine-induced increase in malondialdehyde/nitrite generation and acetylcholinesterase activity and deficit in antioxidant enzyme activity in the hippocampus and prefrontal cortex. Findings from this study showed that the diastereomeric mixture of calophyllic acid and isocalophyllic acid possesses anti-amnesic effect through enhancement of antioxidant defense and cholinergic signaling pathway.