Agathisflavone isolated from Schinus polygamus (Cav.) Cabrera leaves prevents scopolamine-induced memory impairment and brain oxidative stress in zebrafish (Danio rerio)

Abstract

Background: Agathisflavone, a biflavonoid isolated from Schinus polygamus (Cav.) Cabrera leaves been reported to promote various biological activities such as anti-inflammatory properties, promoting cognition and preventing cancer, antioxidant and antiapoptotic activities.

Purpose: Here, we tested the hypothesis whether anxiety, amnesia, and brain oxidative stress induced by scopolamine could be counteracted in zebrafish model by agathisflavone and tried to ascertain the underlying mechanism.

Methods: Agathisflavone (1, 3 and 5 µg/l) was administered by immersion to zebrafish once daily for 8 days period. Anxiety and memory impairment were induced with scopolamine (100 µM) and measured with the novel tank diving test (NTT) and the Y-maze test. Zebrafish were divided into seven groups (n = 20/group): first group - control, second group - scopolamine (100 μM), the third, fourth and fifth group - agathisflavone treatment groups (FAB, 1 µg/l, 3 µg/l, and 5 µg/l), the sixth group - imipramine (IMP, 20 mg/l, as the positive control in NTT test), and the seventh group - donepezil group (DP, 10 mg/l, as the positive control in Y-maze test). The identification of the agathisflavone was done by spectroscopy, and the structure of the compound was confirmed by (-) Electrospray Ionisation Mass Spectrometry (ESI-MS). The brain oxidative status and acetylcholinesterase (AChE) activity were also investigated.

Results: Agathisflavone from Schinus polygamus (Cav.) Cabrera leaves was identified. Also, we demonstrated that agathisflavone significantly reversed scopolamine-induced behavioral score alteration in the NTT and Y-maze tests. Consequently, agathisflavone promoted inhibition of AChE activity and restored the brain antioxidant status.

Conclusion: Our results demonstrate that agathisflavone promotes brain antioxidant action and ameliorates scopolamine-induced anxiety and memory deficits in zebrafish.

Keywords: Agathisflavone; Alzheimer's disease; Memory; Oxidative stress; Schinus polygamus; Scopolamine.