Research Article ISSN: 2574 -1241 DOI: 10.26717/BJSTR.2023.50.007974 Ameliorative Potential of Rutin on Glyphosate-induced Cognitive Dysfunction in Adult Zebrafish Model via Antioxidant and Acetylcholinesterase Inhibitory Actions Lim Shan Rou 1 , Nabila Perveen 1 , Naeem Hasan Khan 1 and Arunachalam Muthuraman 2 * 1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, AIMST University, 08100-Bedong, Kedah D.A., Malaysia 2 Department of Pharmacology, Faculty of Pharmacy, AIMST University, 08100-Bedong, Kedah D.A, Malaysia *Corresponding author: Arunachalam Muthuraman, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, AIMST University, 08100-Bedong, Kedah D.A., Malaysia Copyright@ : Arunachalam Muthuraman | Biomed J Sci & Tech Res | BJSTR. MS.ID.007974. 41794 ABSTRACT Rutin is a bioflavonoid and plant pigment. It is found in various fruits and vegetables. Chemically, it is known as rutoside, quercetin-3-O-rutinoside, sophorin, and vitamin P. It has antioxidant, anti-inflammatory, and immunomodulation-associated neuroprotective and anti- Alzheimer actions. The role of rutin against glyphosate-induced cognitive dysfunction in adult zebrafish has not been studied yet. The present study focused on the role of rutin on glyphosate- induced cognitive dysfunction in adult zebrafish. The glyphosate (GYP, 0.5 mg/L), rutin (50, 100, and 150 µg/L), and donepezil (DP, 1 µg/mL) for 30 minutes/day were exposed for 14 consecutive days. On the 14th day, the neurobehavioural changes were assessed by three horizontal compartment test, optokinetic motor response (OMR), startle response (SR), and T-maze tests. On the 15th day, animals were sacrificed and brain biomarker changes i.e., brain acetylcholinesterase (AChE) activity, thiobarbituric acid reactive substances (TBARS), and reduced glutathione (GSH) levels were estimated. The exposure to rutin ameliorated the GYP-induced cognitive dysfunctions and changes in tissue biomarkers. The results are similar to DP-exposed animals. Hence, rutin can be useful for the treatment of herbicide toxicity like GYP-associated neurocognitive disorders viz anti-oxidant, anti- lipid peroxidation, and modulatory action of cholinergic neurotransmitter activities. Keywords: Cholinergic Neurotransmitter; Optokinetic Motor Response; Reduced Glutathione; Startle Response Test; Thiobarbituric Acid Reactive Substances; Three Horizontal Compartment Test; T-Maze Test ARTICLE INFO Received: May 16, 2023 Published: May 23, 2023 Citation: Lim Shan Rou, Nabila Per- veen, Naeem Hasan Khan and Aruna- chalam Muthuraman. Ameliorative Po- tential of Rutin on Glyphosate-induced Cognitive Dysfunction in Adult Zebraf- ish Model via Antioxidant and Ace- tylcholinesterase Inhibitory Actions. Biomed J Sci & Tech Res 50(4)-2023. BJSTR. MS.ID.007974. Introduction Cognitive dysfunction is mainly indicating attention deficits, verbal and non-verbal learning impairments, amnesia, dementia, alteration of visual & auditory processing, difficulty to solve problems, and changes in motor functions [1,2]. As per the Centers for Disease Control and Prevention (CDC) report, the prevalence rate of cognitive dysfunctions is 11.1% of the population, or 1 adult in every 9 adult persons. In above 65 years aged population is 11.7% and 10.8% of patients between 45-64 years of age [3]. Environmental pollutants i.e., pesticides are one of the risk factors for the development of cognitive impairment [4]. Current experimental evidence also revealed that the herbicide also causes cognitive dysfunction in rats via synaptic impairment and hippocampal neuron damage [5]. Glyphosate (GYP, herbicide) is one of the neurotoxic agents and causes neuronal damage [6]. Furthermore, it also alters the neurotransmitter levels leading to inducing neurobehavioural alterations [7]. The higher concentration of GYP in the nervous system shows monoaminergic neurotransmitter alteration i.e., serotonin (5-HT, 5-hydroxytryptophan), dopamine (DA), and norepinephrine (NE) levels which are responsible for anxiety, fears, defensive, visual-motor functions [7,8]. Furthermore, the level of acetylcholine (ACh) neurotransmitter levels are also modulated by GYP via modulation of acetylcholinesterase enzyme activity which leads to alters the learning & memory functions [9]. The exposure