Different anticonvulsive effects of hesperidin and its aglycone hesperetin on electrical activity in the rat hippocampus in-vitro

This study investigated the possibility that hesperidin or hesperetin might interact directly with brain matter in a physiological manner. The effects of both compounds were followed in the invitro hippocampus preparation by continuous superfusion in a concentration-dependent manner in the presence of single stimuli and theta-burst stimulation of the Schaffer Collaterals. Hesperidin increased the population spike response at a concentration up to 10 mu M, especially after induction of long-term potentiation, but attenuated it significantly at higher concentrations of up to 60 mu M. Hesperetin only attenuated the response within the same concentration range. Modulation of the pyramidal cell response in the presence of tetraethylammonium (TEA) and pentylentetrazol on one hand and 4-aminopyridine (4-AP) and bicuculline on the other was influenced in a different way. Whereas hesperidin attenuated the response to 4-AP and bicuculline but not to TEA or pentylentetrazol, hesperetin was able to attenuate the response to TEA and pentylentetrazol, but not to 4AP or bicuculline. This feature was reproduced and confirmed ex-vivo, after repetitive administration of hesperidin and hesperetin in-vivo for one week (500 mg kg(-1) orally) before in-vitro testing against the challenging effects of 4-AP and TEA. Since the action of hesperidin was sensitive to the presence of iberiotoxin, the involvement of a large conductance calcium-dependent potassium channel might be assumed. In summary, the results provide the possibility for use of both compounds to control pathophysiological disturbances of brain excitability in drug abuse, migraine and epilepsy.