Amelioration of Cognitive Deficit by Cryptotanshinone in a Long-term Utilisation of Proton Pump Inhibitor-Induced Alzheimer's Disease-Like Condition in a Rat Model

Lansoprazole is a proton pump inhibitor, used to treat acid-related diseases, like reflux esophagitis, gastric and duodenal ulcers, and Zollinger-Ellison syndrome. Cryptotanshinone is the major active diterpenoid obtained from the component of Salvia, Lamiaceae, and possesses various beneficial pharmacological properties like anti-amyloidogenic, anti-apoptosis, antioxidant, anti-inflammatory, and neuroprotective effects. The aim of the present study was to find out the neuroprotective effect of cryptotanshinone through in vitro and in vivo experiments approaches in lansoprazole-induced aggregated amyloid-beta accumulation in the rats associated with producing Alzheimer's disease-like symptoms. Cryptotanshinone inhibits acetylcholinesterase and butyrylcholinesterase enzyme activity in a concentration-dependent manner. Lansoprazole at 30 mg/kg for 4 weeks was used to induce Alzheimer's disease-like symptoms, and cryptotanshinone (10 and 20 mg/kg, i.p.) was administrated for 4 weeks to treat the disease. Daily administration of cryptotanshinone dose-dependently prevented memory impairments, as confirmed by the Morris water maze, actophotometer, and elevated plus maze apparatus. On day 29, rats were sacrificed, and the brains were isolated for estimation of neuroinflammatory, biochemicals, neurotransmitters, amyloid-beta (1-42) level, and histopathological and immunohistochemistry analysis. Rats treated with cryptotanshinone exhibited improved recognition and spatial memory, restored antioxidant enzymes and neurotransmitter concentration, and attenuated proinflammatory cytokine release dose-dependently. Cryptotanshinone also decreased the level of amyloid-beta (1-42) and improved the activity of -Na+/K+ ATPase in the hippocampus. The histological and immunohistochemistry analysis showed that cryptotanshinone reduced neuronal death and modulated the nuclear factor erythroid-2-related factor-2 signalling pathway altered by lansoprazole in the hippocampus.