The chemical structure of schisandrin B.

The effect of schisandrin B (0.75–3 µM) on PTZ-induced seizure-like activity in zebrafish larvae. The data are expressed as distance traveled (in mm) by larvae in 2 min-long time bins (A); total distance covered by larvae during 30 min of the assay (B). Data are analyzed using two-way or one-way ANOVAs with Bonferroni’s or Tukey’s post hoc tests, respectively. Data are presented as mean ± standard error of the mean (SEM). Group schisandrin B 3 µM + vehicle consisted of 36 zebrafish larvae, group schisandrin B 0.75 µM + PTZ consisted of 46 larvae, and the remaining experimental groups had 48 zebrafish larvae. *** p < 0.001 vs. vehicle + vehicle-treated group; ^{^^^} p < 0.001 vs. vehicle + PTZ-treated group. PTZ, pentylenetetrazole.

The effect of schisandrin B on epileptiform-like activity in the optic tectum of larval zebrafish treated with PTZ. Six-day-old fish were incubated with schisandrin B (3 µM) for 24 h and subsequently exposed to PTZ (20 mM). After a 5 min delay, LFP recordings from the larval optic tectum were obtained. Data are shown as: number of events (nr/20 min) (A); mean duration of events (s/20 min) (B); and representative LFP recordings (C). Data were analyzed using one-way ANOVA followed by Tukey’s post hoc test. Data are depicted as individual measurements (as symbols) and mean values. The experimental groups consisted of the following number of zebrafish larvae: vehicle + vehicle − 9, vehicle + PTZ − 15, schisandrin B + vehicle − 5, and schisandrin B + PTZ − 13. *** p < 0.001 vs. vehicle + vehicle; ^{^^^} p < 0.001, ^{^^}p < 0.01 vs. vehicle + PTZ. PTZ, pentylenetetrazole.

The effect of schisandrin B on c-fos (A) and bdnf (B) mRNA expressions in PTZ-bathed larval zebrafish. Six-day-old fish were incubated with schisandrin B (3 µM) for 24 h and subsequently exposed to PTZ (20 mM). After a 90 min delay, fish were collected and pooled (10/sample). Data were analyzed using one-way ANOVA with the Tukey’s post hoc test. Data are depicted as individual measurements (as symbols) and mean + SEM (n = 8/group). *** p < 0.001 vs. vehicle + vehicle; ^{^^^}p < 0.001, ^{^^} p < 0.01 vs. vehicle + PTZ. PTZ − pentylenetetrazole.

The effect of schisandrin B on hatching at 72 and 96 hpf (A); swim bladder inflation (B); yolk sac abnormalities (C); heart malformation (D); hemorrhage (E) and body shape of 96 hpf old larvae (F). Zebrafish larvae were exposed to schisandrin B at a concentration range of 0.375–6 µM for 95 h. All scores were performed in triplicates and the results were pooled together. The experimental groups consisted of the following number of zebrafish larvae: vehicle + vehicle − 36, schisandrin B 0.375 µM − 32, schisandrin B 0.75 µM − 33, schisandrin B 1.5 µM − 36, schisandrin B 3 µM − 36, schisandrin B 6 µM − 34. * p < 0.05; ** p < 0.01; *** p < 0.001 vs. control group, Fisher’s exact test.

Representative images of the zebrafish larvae from the toxicity test. One hpf zebrafish embryo was exposed to different concentrations of schisandrin B (from 0.375 to 6 µM) for 95 h and, afterwards, pictures of the representative zebrafish larvae were taken. Larvae are shown to the same scale (bar = 1 mm).

The effect of schisandrin B (3 µM) on zebrafish larval behavior in the light–dark and thigmotaxis tests. The data are shown as: distance traveled (in mm) by larvae when exposed to alternating light (100%) and dark (0%) conditions in 1 min-long time bins (A), aggregate data over the entire stimulus duration (10 min) (B), the percentage of time that the larvae are located in the outer zone of the swimming area when exposed to alternating light (100%) and dark (0%) conditions (C). Data were analyzed using two-way repeated measures with Tukey’s post hoc test. Data are presented as individual measurements (as symbols) and mean ± SEM. All experimental groups consisted of 18 zebrafish larvae. Letters indicate significant differences within treatment groups: a. comparison from light to dark phase, b. comparison from dark to light phase; ** p < 0.01.

LogBB values calculated for schisandrin B. logBB in silico—the value calculated using ACD/Percepta software, logBB-QSAR—the value calculated based on Equation (1), and logBB-IAM—the value determined from the biomimetic IAM system.

Mass chromatogram recorded in the positive ionization mode for the reference solution of schisandrin B (concentration 1 mg/mL, injection volume: 10 µL) (A); extracted ion chromatogram of schisandrin B in brain tissue recorded in the positive ionization mode (B), and changes in schisandrin B concentration in the blood plasma (C) and brain tissue (D) at 8 time points, i.e., 15 and 30 min as well as 1, 2, 4, 8, 12, and 24 h, after its ip administration at a dose of 50 mg/kg in mice. Plasma and brain concentrations of schisandrin B are presented as mean ± standard deviation (SD) (n = 6).

The time–course effect of schisandrin B (50 mg/kg, ip) on the threshold for myoclonic twitches (A), generalized clonic seizures with the loss of righting reflex (B), and tonic seizures (C) in the iv PTZ test in mice. Control group and groups tested 30 and 240 min after schisandrin B treatment consisted of 11 mice while groups tested 60 and 120 min after schisandrin B treatment had 12 animals. Data were analyzed using one-way ANOVA with the Tukey’s post hoc test. Data are depicted as mean ± SEM. White bars represent the control groups while colored represent schisandrin B-treated groups.

Molecular interactions of schisandrin B with D₂ receptor (A,B,E) and 5-HT_2A receptor (C,D,F) based on molecular docking. (A,C) Overview of ligand pose in the receptor. Receptor shown in gray in cartoon representation, ligand shown as blue balls; (B,D) 3D details of the binding site. The most important protein residues are shown as sticks with gray carbon atoms. Ligand shown as sticks with blue carbon atoms; (E,F) 2D overview of the binding site.

Molecular interactions of schisandrin B with NMDA receptor based on molecular docking. (A) Overview of ligand pose in the receptor. Receptor shown in gray in cartoon representation, ligand shown as blue balls; (B) 3D details of the binding site. The most important protein residues are shown as sticks with gray carbon atoms. Ligand shown as sticks with blue carbon atoms. Polar interactions shown as red dashed lines; (C) 2D overview of the binding site.

Molecular interactions of schisandrin B with GABA_A receptor based on molecular docking. (A) Overview of ligand pose in the receptor. Receptor shown in gray in cartoon representation, ligand shown as blue balls; (B) 3D details of the binding site; (C) 2D overview of the binding site.