Daidzein ameliorates nonmotor symptoms of manganese‐induced Parkinsonism in zebrafish model: Behavioural and biochemical approach

Author:

Haridevamuthu Balasubramanian1ORCID,Sudhakaran Gokul1ORCID,Pachaiappan Raman2ORCID,Kathiravan Muthu Kumaradoss3ORCID,Manikandan Krishnan4ORCID,Almutairi Mikhlid H.5ORCID,Almutairi Bader O.5ORCID,Arokiyaraj Selvaraj6ORCID,Arockiaraj Jesu7ORCID

Affiliation:

1. Center for Global Health Research, Saveetha Medical College and Hospital Saveetha Institute of Medical and Technical Sciences (SIMATS) Chennai Tamil Nadu 600105 India

2. Department of Biotechnology, School of Bioengineering, Faculty of Engineering and Technology SRM Institute of Science and Technology Kattankulathur, Chengalpattu District Tamil Nadu 603203 India

3. Dr APJ Abdul Kalam Research Lab, Department of Pharmaceutical Chemistry, SRM College of Pharmacy SRM Institute of Science and Technology Kattankulathur, Chengalpattu District Tamil Nadu 603203 India

4. Department of Pharmaceutical Analysis, SRM College of Pharmacy SRM Institute of Science and Technology Kattankulathur, Chengalpattu District Tamil Nadu 603203 India

5. Department of Zoology, College of Science King Saud University P.O. Box 2455, Riyadh, 11451 Saudi Arabia

6. Department of Food Science & Biotechnology Sejong University Seoul 05006 Korea

7. Toxicology and Pharmacology Laboratory, Department of Biotechnology, Faculty of Science and Humanities SRM Institute of Science and Technology Kattankulathur, Chengalpattu District Tamil Nadu 603203 India

Abstract

AbstractBackground and PurposeParkinson's disease (PD) is a prevalent neurodegenerative movement disorder characterized by motor dysfunction. Environmental factors, especially manganese (Mn), contribute significantly to PD. Existing therapies are focused on motor coordination, whereas nonmotor features such as neuropsychiatric symptoms are often neglected. Daidzein (DZ), a phytoestrogen, has piqued interest due to its antioxidant, anti‐inflammatory, and anxiolytic properties. Therefore, we anticipate that DZ might be an effective drug to alleviate the nonmotor symptoms of Mn‐induced Parkinsonism.Experimental ApproachNaïve zebrafish were exposed to 2 mM of Mn for 21 days and intervened with DZ. Nonmotor symptoms such as anxiety, social behaviour, and olfactory function were assessed. Acetylcholinesterase (AChE) activity and antioxidant enzyme status were measured from brain tissue through biochemical assays. Dopamine levels and histology were performed to elucidate neuroprotective mechanism of DZ.Key ResultsDZ exhibited anxiolytic effects in a novel environment and also improved intra and inter fish social behaviour. DZ improved the olfactory function and response to amino acid stimuli in Mn‐induced Parkinsonism. DZ reduced brain oxidative stress and AChE activity and prevented neuronal damage. DZ increased DA level in the brain, collectively contributing to neuroprotection.Conclusion and ImplicationsDZ demonstrated a promising effect on alleviating nonmotor symptoms such as anxiety and olfactory dysfunction, through the mitigation of cellular damage. These findings underscore the therapeutic potential of DZ in addressing nonmotor neurotoxicity induced by heavy metals, particularly in the context of Mn‐induced Parkinsonism.

Publisher

Wiley

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