Title:Ameliorative Effect of Acetyl L-carnitine in Alzheimer's Disease via Downregulating
of Homocysteine Levels in Hyperhomocysteinemia Induced Cognitive
Deficit in Mouse Model
Volume: 14
Issue: 3
Author(s): Nisha Verma, Jeetendra Kumar Gupta, Krishna Kumar Varshney and Rajnish Srivastava*
Affiliation:
- Moradabad Educational Trust Group of
Institutions Faculty of Pharmacy, Moradabad, Uttar Pradesh, India
Keywords:
Acetyl L-carnitine, methyl donor, sodium orthovanadate, hyperhomocysteinemia, alzheimer’s disease, prefrontal cortex.
Abstract: Aims: The study was aimed at exploring the role of Acetyl L-Carnitine supplementation
attenuating dementia and degradation of cognitive abilities in Hyperhomocysteinemia induced AD
manifestations in the mouse model.
Background: Alzheimer’s disease (AD) is a neurological disorder that is marked by dementia, and
degradation of cognitive abilities. There is great popularity gained by natural supplements as the
treatment for AD, due to the higher toxicities of synthetic drugs. Hyperhomocysteinemia causes
excitotoxicity to the cortical neurons, which brought us to the point that amino acids possibly have
a role in causing cholinergic deformities, which are an important etiological parameter in AD.
Acetyl L-Carnitine a methyl donor with the presence of three chemically reactive methyl groups
linked to a nitrogen atom was found to possess neuroprotective activity against experimental models
of AD.
Objective: The objective of the present investigation was to investigate and evaluate the pharmacological
effect of Acetyl L-Carnitine against hyperhomocysteinemia induced Alzheimer’s disease
(AD) in the mouse model.
Materials and Methods: The animals were divided into normal control (vehicle-treated), HHcy
(dl-Homocysteine thiolactone treated) negative control, test group i.e., low dose (50mg/kg, p.o) of
acetyl L-carnitine (L-ALC), high dose (100mg/kg,p.o) of acetyl L-carnitine (H-ALC), L-ALC+
SOV (Sodium orthovanadate) and H-ALC+SOV. HHcy was induced by administration of dl-Homocysteine
thiolactone (dl-HCT; 1 g/kg, p.o.) on day-1 to day-15 of experimental schedule to all
animals except normal control. The changes in the behaviour pattern of the animals due to neuroinflammation,
and cholinergic dysfunction were examined in rotarod, novel objective recognition,
passive avoidance, elevated plus maze, and morris water maze analysis. Biochemical investigation
includes the estimation of total homocysteine (tHcy), Creatinine Kinase (CK), Acetylcholinesterase
(AChE), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and IL-6
and TNF-α.
Results: Supplementation of ALC in mouse considerably lowered the HHcy-induced AD manifestations
in the experimental animals. It was found that ALC and SOV successfully diminished the
behaviour abnormalities and lessened the Hcy-induced alteration in systemic Hcy levels, CK activity,
and cholinergic dysfunction with improved bioenergetics in the Prefrontal cortex of the mice.
Conclusion: ALC was found to improve the HHcy-induced cognitive disabilities which was found
to be associated with the decreased systemic levels of Hcy, CK, and cholinergic abnormalities. It also
combats the oxidative stress-induced neuroinflammation with diminished pro-inflammatory
markers in the pre frontal cortex. The outcomes collectively indicate ALC's potential to be used as
a supplementation in the pharmacotherapy of AD.