Fisetin decreases the duration of ictal-like discharges in mouse hippocampal slices.

There is an increasing interest in the biological and therapeutic effects of fisetin, a natural phenolic compound. Fisetin has affinity on some neuronal targets and may have the potential to modulate neuronal activity. In this study the effects of acute application of fisetin on synchronized events were evaluated electro-physiologically. Besides, interaction of fisetin with closely related channels were investigated in silico. Acute horizontal hippocampal slices were obtained from 32- to 36-day-old C57BL/6 mice. Extracellular field potentials were recorded from CA3 region of the hippocampus. Bath application of 4 aminopyridine (4AP, 100 µM) initiated ictal- and interictal-like synchronized epileptiform discharges in the brain slices. Fifty micromolar fisetin was applied to the recording chamber during the epileptiform activity. The duration and frequencies of both ictal-like and interictal-like activities were calculated from the electrophysiological records. Molecular docking was performed to reveal interaction of fisetin on GABA-A, NMDA, AMPA receptors, and HCN2 channel, which are neuronal structures directly involved in recorded activity. Although fisetin does not affect basal neuronal activity in brain slice, it reduced the duration of ictal-like discharges significantly. Molecular docking results indicated that fisetin has no effect on GABA-A, NMDA, and AMPA receptors. However, fisetin binds to the (5JON) HCN2 channel strongly with the binding energy of -7.66 kcal/mol. Reduction on the duration of 4AP-induced ictal-like discharges can be explained as HCN channels can cause an inhibitory effect via enhancing M-type K + channels which increase K outward currents.

In silicoinvestigation of Alliin as potential activator for AMPA receptor.

Natural products from plants, such as flavonoids, arouse immense interest in medicine because of the therapeutic and many other bioactive properties. The molecular docking is a very useful method to screen the molecules based on their free binding energies and give important structural suggestions about how molecules might activate or inhibit the target receptor by comparing reference molecules. Alliin and Allicin differ from many other flavonoids because of containing no benzene rings and having nitrogen and sulfur atoms in their structure. In this study Alliin and Allicin affinity on AMPA, NMDA and GABA-A receptors were evaluated in the central nervous system by using the molecular docking method. Both Alliin and Allicin indicated no inhibitory effects. However Alliin showed significant selectivity to human AMPA receptor (3RN8) as an excitatory. The binding energy of glutamate to 3RN8 was -6.61 kcal mol-1, while the binding energy of Allin was -8.08 kcal mol-1. Furthermore Alliin's affinity to the other AMPA and NMDA receptors is quite satisfactory compared to the reference molecule glutamate. In conclusion based on the molecular docking study, Alliin can be useful for synaptic plasticity studies whereas might be enhance seizure activity because of the increased permeability to cations. It also can be beneficial to improve learning and memory and can be used as a supportive product to the hypofunction of NMDA associated problems.