Protective effect of intranasal asiatic acid in scopolamine-induced memory impairment in mice

Asiatic acid (AA), a major constituent of Centella asiatica extract, possesses various pharmacological activities including antioxidant, anti-inflammation, and neuroprotective effects. Low oral bioavailability has limited AA penetration to the brain. The intranasal administration increases the efficacy of drug by passing blood brain barrier and by avoiding the metabolism by hepatic enzyme. This study investigated the protective effect and the mechanisms of intranasal asiatic acid in scopolamine-induced memory impairment in mice. Mice are divided into seven groups; control (Con), scopolamine (3 mg/kg; Sco), scopolamine plus donepezil (3 mg/kg; Don), scopolamine plus intranasal asiatic acid (2.31 mg/kg; INAA) and scopolamine plus oral asiatic acid (3, 30, and 100 mg/kg; POAA3, POAA30, and POAA100). The treatments were given 10 consecutive days, 30 min before the behavioral tests. Morris water maze was performed on days 0-8. Locomotor activity was tested on day 9. Brains were kept on day 10. Morris water maze results revealed that INAA and POAA3 significantly decreased escape latency on day 3 (p < 0.05 vs Sco). INAA also increased time spent in the target quadrant in the probe trial (p < 0.05 vs Sco). INAA also inhibited acetylcholine esterase activity in the hippocampus and prefrontal cortex (p < 0.05 vs Sco). INAA increased catalase expression in the hippocampus and decreased brain malondialdehyde level (p < 0.05 vs Sco). Additionally, the intranasal asiatic acid increases brain-derived neurotrophic factor (BDNF) compared to the oral asiatic acid (p<0.05). In conclusion, INAA prevent scopolamine-induced memory impairment by inhibiting the activity of acetylcholinesterase activity, by increasing the catalase, BDNF level and by decreasing lipid peroxidation.