Nattokinase prevents β-amyloid peptide (Aβ1-42) induced neuropsychiatric complications, neuroinflammation and BDNF signalling disruption in mice

Shivraj Naik; Raj Katariya; Shraddha Shelke; Vandana Patravale; Milind Umekar; Nandkishor Kotagale; Brijesh Taksande

doi:10.1016/j.ejphar.2023.175821

Nattokinase prevents β-amyloid peptide (Aβ_1-42) induced neuropsychiatric complications, neuroinflammation and BDNF signalling disruption in mice

Eur J Pharmacol. 2023 Aug 5:952:175821. doi: 10.1016/j.ejphar.2023.175821. Epub 2023 May 30.

Authors

Shivraj Naik¹, Raj Katariya², Shraddha Shelke², Vandana Patravale¹, Milind Umekar², Nandkishor Kotagale³, Brijesh Taksande⁴

Affiliations

¹ Pharmaceutical Science & Technology, Institute of Chemical Technology, Matunga, Mumbai, 400019, India.
² Smt. Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur, MS, 441 002, India.
³ Government College of Pharmacy, Kathora Naka, VMV Road, Amravati, MS, 444604, India.
⁴ Smt. Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur, MS, 441 002, India. Electronic address: brijeshtaksande@gmail.com.

PMID: 37263404
DOI: 10.1016/j.ejphar.2023.175821

Abstract

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder characterized by abnormal accumulation of extracellular β-amyloid (Aβ) plaques and neuronal damage. Although AD is typically considered a cognitive neurodegenerative disorder, almost all people diagnosed with AD develop neuropsychiatric complications at some stage in their life span. The present study investigated the effect of chronic Nattokinase (NK) administration on β-Amyloid peptide (Aβ_1-42) induced neuropsychiatric conditions (depression-like behaviour, anxiety, and memory impairment) in mice. Aβ_1-42 peptide injected mice demonstrated depression, anxiety, and impairment of cognitive abilities evaluated as increased immobility time in forced swim test (FST), decreased open arm time/entries in elevated plus maze (EPM) and reference and working memory error in radial arm maze (RAM) respectively with elevation in Interleukin-6 (IL-6), Tumour necrosis factor-α (TNF-α), reduction in Interleukin-10 (IL-10) and Brain-derived neurotrophic factor (BDNF) immunocontent within the hippocampus. Chronic administration of NK (50-100 mg/kg, i.p.) from day 8-27, prevented depression-like behaviour, anxiety, and memory impairment and normalized the neurochemical alteration within the hippocampus of mice injected with Aβ_1-42 peptide. The effect of NK on psychiatric complications, learning, and memory was comparable to peripheral donepezil treatment. This study suggests that NK improves learning, memory impairment, and neuropsychiatric complications possibly through the downregulation of neuroinflammatory pathways and restoring BDNF signalling in AD.

Keywords: Alzheimer's disease; Anxiety; Depression; Memory impairment; Nattokinase; Neuroinflammation; β-amyloid (Aβ(1-42)) peptide.

MeSH terms

Alzheimer Disease* / chemically induced
Alzheimer Disease* / drug therapy
Alzheimer Disease* / metabolism
Amyloid beta-Peptides / metabolism
Animals
Brain-Derived Neurotrophic Factor* / metabolism
Disease Models, Animal
Hippocampus
Maze Learning
Memory Disorders / chemically induced
Memory Disorders / drug therapy
Memory Disorders / prevention & control
Mice
Neuroinflammatory Diseases
Peptide Fragments / pharmacology
Subtilisins* / therapeutic use

Substances

Amyloid beta-Peptides
amyloid beta-protein (1-42)
Brain-Derived Neurotrophic Factor
nattokinase
Peptide Fragments
Subtilisins