Chebulinic Acid Negated the Development of Streptozotocin- Induced Experimental Dementia in Rats

Background: With the constant failure of the clinical trials and continuous exploration of a therapeutic target against Alzheimer’s disease (AD) is the utmost needed. Chebulinic acid (ChA) has been reported to possess neuroprotective potential in various neurodegenerative models such as anxiety and depression. Materials and Methods: In the current study, the ChA was challenged on the progression of AD induced by intracerebroventricular (ICV)-streptozotocin (STZ)-induced neurotoxicity to determine its therapeutic potential in experimental dementia. STZ was infused bilaterally (3 mg/kg/icv) on day 1st and 3rd after surgery. ChA (25, 50 and 100 mg/kg/p.o) was administered from 7th day onwards up to 21st day following 1st ICV-STZ infusion. Cognitive impairment was evaluated by actophotometer, Morris water maze (MWM) and object recognition task (ORT) in rats whereas biochemical, neurochemical, neuroinflammatory were evaluated using hipoocampal brain regions on day 22nd. Results: Ventricular administration of STZ in rats found to significantly shorten the latency time on the MWM and ORT which was associated with significant alterations in hippocampal biochemistry, including elevation in oxidative stress and compromised antioxidant defense, neurotransmitter alteration and elevation in neuroinflammatory cytokine levels. ChA treatment significantly prevented the ICVSTZ- induced memory deficit by attenuating the hippocampal neuronal loss, neuroinflammation and compromised antioxidant defense and cholinergic deficits in rats. Conclusion: These results clearly pointed to the pivotal role of ChA in ICV-STZ induced neurotoxicity and its association may be a promising alternative to be investigated in the treatment of AD-like dementia.