Baicalein 5,6-Dimethyl Ether Prevents Memory Deficits in the Scopolamine Zebrafish Model by Regulating Cholinergic and Antioxidant Systems

Abstract

Baicalein 5,6-dimethyl ether, a bioactive flavonoid isolated for the first time from Alnus rugosa, was explored for its capability to relieve memory deficits and decrease oxidative stress. We examined the neuropharmacological effects of baicalein 5,6-dimethyl ether on scopolamine (Sco)-induced zebrafish (Danio rerio) anxiety, amnesia, and brain oxidative stress and attempted to elucidate the underlying mechanisms. Anxiety-like behavior, exploratory behavior, and memory performance were measured using novel tank-diving test (NTT), Y-maze, and novel object recognition (NOR) tests. For 10 days, baicalein 5,6-dimethyl ether (1, 3, and 5 µg/L) was administered through immersion, whereas Sco (100 μM) was delivered 30 min before behavioral tests. Treatment with baicalein 5,6-dimethyl ether reduced anxiety and memory impairment, and increased exploratory behavior in specific tests, along with significant protection from neuronal oxidative stress in the brain tissue of Sco-treated zebrafish. Antioxidant and anti-acetylcholinesterase (AChE) activities of baicalein 5,6-dimethyl ether in the Sco-induced zebrafish were further confirmed using in vivo assays. In Sco-treated zebrafish, baicalein 5,6-dimethyl ether regulated cholinergic function by inhibiting AChE activity. Baicalein 5,6-dimethyl ether may be a promising candidate compound for treating anxiety and amnesia by restoring cholinergic activity and reducing brain oxidative stress, according to our findings.

Baicalein-corrected gut microbiota may underlie the amelioration of memory and cognitive deficits in APP/PS1 mice

“…One example of such herbal medicine is Scutellaria baicalensis Georgi. Baicalein is the main bioactive ingredient in this herbal plant, with anti-inflammatory, antioxidant, and cognitive-enhancing properties ( Brinza et al, 2021 ; Gregory et al, 2021 ). Our previous study showed that chronic treatment of Baicalein ameliorates cognitive dysfunction in the novel object recognition and Morris water maze tests in the Aβ-treated mouse model of AD ( Shi et al, 2021 ).…”

Baicalein prevents stress-induced anxiety behaviors in zebrafish model

“…As a reason, zebrafish embryo toxicity testing looks promising as a preliminary screening technique and perhaps even as a stand-in for mammalian toxicity testing. Baicalein and its derivatives have been carried out for a toxicity study in zebrafish model ( Jiang et al, 2018 ; Zhang et al, 2020 ; Brinza et al, 2021 ). No toxicity was observed at the chosen dose/concentration levels, which were selected based on previous investigations that were reported in the literature ( Jiang et al, 2018 ; Zhang et al, 2020 ; Brinza et al, 2021 ).…”

“…Baicalein and its derivatives have been carried out for a toxicity study in zebrafish model ( Jiang et al, 2018 ; Zhang et al, 2020 ; Brinza et al, 2021 ). No toxicity was observed at the chosen dose/concentration levels, which were selected based on previous investigations that were reported in the literature ( Jiang et al, 2018 ; Zhang et al, 2020 ; Brinza et al, 2021 ). Further, to explore toxicity testing, the brine shrimp lethality assay has also been recommended ( Rajabi et al, 2015 ).…”

Origanum vulgare ssp. hirtum (Lamiaceae) Essential Oil Prevents Behavioral and Oxidative Stress Changes in the Scopolamine Zebrafish Model

“…For the biochemical assay, all zebrafish were cryoanesthetized and euthanized by decapitation [ 82 ]. The zebrafish brain samples were dissected and gently homogenized in 0.1 M potassium phosphate buffer (pH = 7.4) with 1.15% KCl using a Potter homogenizer (Heidolph Instruments, Schwabach, Germany) coupled with Cole-Parmer Servodyne Mixer (Cole-Parmer Instrument Co., Chicago, IL, USA).…”