Combination of Ocimum sanctum extract and Levetiracetam ameliorates cognitive dysfunction and hippocampal architecture in rat model of Alzheimer's disease

J Chem Neuroanat. 2022 Mar:120:102069. doi: 10.1016/j.jchemneu.2021.102069. Epub 2021 Dec 29.

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disease which affects more than 40 million people worldwide with progressive loss of memory and cognitive functions. It is reported, persistent AD is also one of the main causes of epilepsy in elders and comorbidity of both these will contribute to worsening the health status of AD patients. Recently, herbal plants with potent neuroprotective and antioxidant properties were used for increasing the quality of life in neurodegenerative disease patients. The present study was conceptualized to access the protective effect of Ocimum sanctum extract (OSE) and Levetiracetam (LEV) and their combination (OSE+LEV) against AD and epilepsy associated with AD in the rat AD model. AD was induced in aged male Wistar albino rats with Amyloid-β (Aβ) by intracerebroventricular administration. The results reveal, treatment with OSE, LEV and OSE+LEV significantly reversed the memory impairment, increases the BDNF expressions and decreases AChE activity in Aβ induced AD animals. Expression of A-β and p-tau in the hippocampus was significantly reduced in treatment group when compared to the control animals. Treatment with OSE and OSE+LEV also restored the hippocampal architecture by ameliorating the neuronal count in CA1, CA3 and DG regions. It also observed that treatment has decreased the excitoneurotoxicity evidenced by decreased glutamate and increased GABA levels and thus provided protection against epilepsy. Treatment groups also exhibited a potent antioxidant activity when tested endogenous antioxidant enzymes SOD, GSH and LPO in the brain hippocampus. Our findings provide evidence for use of OSE, LEV and OSE+LEV against AD and epilepsy associated with AD in Aβ induced AD animal model. However, further clinical studies are required to prove the use of OSE, LEV and OSE+LEV in the management of AD and AD-associated epilepsy in human volunteers.

Keywords: Acetylcholinesterase; Amyloid β; BDNF; Cognitive dysfunction; Epilepsy; GABA; Glutamate; Neurodegenerative diseases; Ocimum sanctum.

MeSH terms

  • Aged
  • Alzheimer Disease* / drug therapy
  • Animals
  • Cognitive Dysfunction*
  • Disease Models, Animal
  • Hippocampus
  • Humans
  • Levetiracetam / pharmacology
  • Male
  • Neurodegenerative Diseases*
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use
  • Ocimum sanctum
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Quality of Life
  • Rats
  • Rats, Wistar

Substances

  • Neuroprotective Agents
  • Plant Extracts
  • Levetiracetam