Mechanistic insight into the antistress potential of eugenol: Modulation of the monoaminergic system in chronic unpredictable stress zebrafish model

DOI:
https://doi.org/10.62110/sciencein.cbl.2025.v12.1257Keywords:
Stress, Anxiety, Eugenol, Dopamine, Serotonin, Neuroprotection, nervous system, Brain functions, AntioxidantsAbstract
The unwanted side effects associated with existing therapeutics against anxiety disorder warrants further preclinical investigations to discover new drug candidates. Herein, we report the anti-anxiety effect of Eugenol (EUG), a phytoconstituent, in chronic unpredictable stressed (CUS) model of zebrafish. The zebrafish were exposed to mild stress and the anxiety-like behaviour was quantified using the light-dark test and novel tank tests. It was observed that the stress induced a significant decline in number of entries and the time spent in the light compartment, increased latency to move into the top and spending less time therein and increased freezing duration, which indicated the anxiety in the fish. Interestingly, EUG treatment showed a reversal of behavioural alterations caused by CUS, and suggested the potential therapeutic effect. The reduced concentrations of stress related neurotransmitter monoamines, dopamine (DA) and serotonin (SE) were observed in CUS model during analysis using HPLC coupled with PDA detector. However, significantly increased levels of DA and SE were noted upon EUG treatment. On the other hand, immunohistochemistry studies on brain tissue of zebrafish revealed that the decreased activities of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) enzymes in stressed conditions were significantly increased upon EUG treatment. These results indicated the neuroprotective potential or regulatory role of EUG in stress induced alterations. The finding underscores the importance of exploring natural compounds like EUG for their therapeutic potential against neurochemical modifications caused by stress.