International Journal of Pharmaceutical Investigation, 2020, 10, 1, 24-31.
DOI: 10.5530/ijpi.2020.1.5
Published: March 2020
Type: Original Article
Authors:
Arora Rimpi
[1]Research Scholar, I.K. Gujral Punjab Technical University, Jalandhar, Punjab, INDIA. [2]Neuropharmacology Division, Department of Pharmacology, I. S. F. College of Pharmacy, Moga, Punjab, INDIA.
Deshmukh Rahul
Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University, Bathinda, Punjab, INDIA.
ABSTRACT
Chebulinic acid (ChA) has been reported to possess neuroprotective potential in various neurodegenerative models such as anxiety and depression. In the current study, the ChA was challenged against intracerebroventricular (ICV)-streptozotocin (STZ)-induced neurotoxicity to determine its therapeutic potential in 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. Spatial and non-spatial memory was evaluated and terminally the animals were sacrificed and hipoocampal brain regions were used to identify biochemical and histopathologicsal alterations. Ventricular administration of STZ in rats caused impairment in learning and memory indicating cognitive dysfunctions. The observed cognitive dysfunctions was also associated with significant alterations in hippocampal biochemistry, including elevation in oxidative stress, found to significantly shorten the latency time on the MWM and ORT which was associated with increase in oxidative stress (lipid peroxidation and nitrite), compromised antioxidant defense (reduced glutathione), neurotransmitter alteration (AChE, dopamine, noradrenaline, 5-hydoxytryptamine, Gama amino butyric acid and glutamate) and elevation in neuroinflammatory cytokine (IL-1 β, IL-6 and TNF- α) levels. The number of apoptotic neurons was increased in hippocampus tissue after ICV-STZ administration. The histopathological studies in the brain of rats also supported that ChA markedly reduced the ICV-STZ-induced histopathological changes and well preserved the normal histological architecture of the hippocampus. The study demonstrates the effectiveness of ChA, as a powerful antioxidant, anti-inflammatory and neuromodulatory in preventing the all these detrimental effects induced by STZ. ChA treatment significantly prevented the ICV-STZ-induced memory deficit by attenuating the hippocampal neuronal loss, neuroinflammation and compromised antioxidant defense and cholinergic deficit in rats. Thus, ChA may have a therapeutic value for the treatment of AD.
Keywords: Alzheimer’s Dementia, Chebulinic acid, Streptozotocin, Neuroprotection, Hippocampus.