Gentiana lutea extract ameliorates scopolamine-induced amnesia in mice via cholinergic modulation and inhibition of Aβ/p-tau protein accumulation

Objective: To investigate the potential of hydro-alcoholic extract of Gentiana lutea roots (GLE) in scopolamine-induced amnesia model in mice. Methods: The active chemical constituents were determined by GC-MS analysis. In vitro antioxidant activity was performed by the DPPH free radical scavenging method. Ex vivo anti-acetylcholinesterase assay was conducted to investigate the effect on the cholinergic system. A scopolamine-induced memory impairment model was used. The levels of beta-amyloid (Aβ) and tau protein were measured. The behavioral studies were performed through Morris water maze and passive avoidance learning tests, followed by estimation of biochemical markers (GSH and MDA), immunohistochemistry, and histopathological studies on isolated brain tissues. Results: GLE exhibited DPPH free radical scavenging activity with an IC 50 value of (76.68±2.28) μg/mL. GLE also manifested inhibitory effect on acetylcholinesterase [IC 50 (36.58±0.73) μg/mL] to upregulate the cholinergic system. GLE at 200 mg/kg and 400 mg/kg significantly restored the memory impairment induced by scopolamine. GLE at 200 mg/kg and 400 mg/kg significantly reduced brain oxidative stress ( P <0.001). Immunohistochemistry investigation showed a significant reduction in Aβ deposition and p-tau protein expression in the GLE treatment groups ( P <0.001). Administration of GLE effectively reduced scopolamine-induced neuronal damage in a dose-dependent manner. Conclusions: The study demonstrates that GLE ameliorates scopolamine-induced memory impairment by alleviating Aβ/p-tau protein accumulation and upregulation in the cholinergic system to improve cognitive dysfunction and behavioral problems.