Effects of Methoxyflavone and their Derivatives on Memory Deficits Induced by Scopolamine in Zebrafish Models of Alzheimer’s Disease

Author(s): Nithya Panneerselvam*, Parimala Kathirvelu and Hemanthkumar Shanmugam

Abstract

Background: Dementia, predominantly caused by Alzheimer’s disease (60-70% of cases), represents a significant disease burden. As methoxyflavones from Kaempferia parviflora possess AChE-inhibition properties, synthetic methoxyflavones and their derivatives were chosen for their therapeutic potential in established zebrafish neurodegenerative models.

Aim: To study the effect of methoxyflavone and its synthetic derivatives in scopolamine-induced memory deficit models of Zebrafish.

Methodology: 12 groups of adult Danio rerio (10 fish per tank) were used. A stock solution of all three test drugs (7-methoxyflavone, 7,4’ dimethoxyflavone, and 7,2’,4’ trimethoxyflavone-in doses of 5,10,20 mg), standard Rivastigmine 1.5 mg/kg, and scopolamine 200 μM were prepared & diluted to the desired volume of stock solution in 1 L of system water. Each animal in the designated group was exposed to the drug containing fluid for 60 minutes. Then they were subjected to behavioural models of learning and memory.

Results: In the T-maze analysis, 7-methoxyflavone 20 mg/L showed a more extended time spent ratio (1.230 ± 0.207) and a greater total number of entries ratio (1.4261 ± 0.352) in the green arm, which were moderately comparable with the time spent ratio (1.9568 ± 0.228) and the number of entries ratio (2.345 ± 1.013) in the Rivastigmine group. In the light and dark test, zebrafish that received 7-methoxyflavone at doses of 5 mg/L (151 ± 6.548), 10 mg/L (169.1 ± 7.950), and 20 mg/L (176.2 ± 6.442) had significantly increased the time spent in the light chamber in comparison to the Rivastigmine group (220.9 ± 6.154).

Conclusion: 7-Methoxyflavone in a dose of 20 mg/L exhibited significant cognitive improvement in scopolamine-induced memory deficit models of Zebrafish. These results position it as a prime candidate for further development and research in the treatment of Alzheimer’s disease dementia.

image 10.4303/JDAR/236475

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