3,4,5-Trimethoxycinnamic acid, one of the constituents of Polygalae Radix exerts anti-seizure effects by modulating GABAAergic systems in mice

Polygalae Radix is an important medicinal plant that is widely used in most of Africa. 3,4,5-Trimethoxycinnamic acid (TMCA) is one of the constituents of Polygalae Radix. Until now, the mechanisms involved in the anti-seizure property of TMCA are still unclear. We examined the anti-seizure effect of TMCA. TMCA administered at doses of 5, 10 and 20 mg/kg and evaluated anti-seizure effects by maximal electroshock (MES) and pentylenetetrazol (PTZ) models in mice. TMCA administered at doses of 10 and 20 mg/kg significantly reduced the incidence of MES-induced tonic hindlimb extension (THE). TMCA significantly delayed the onset of myoclonic jerks (MJ), and decreased the seizure severity and mortality compared with the vehicle-treated animals in PTZ seizure model. TMCA 10 and 20 mg/kg treated groups also did not determined generalized clonic seizures (GCS).Pretreatment with a GABAA/benzodiazepine (BZ) receptor antagonist flumazenil blocked the anti-seizure effects of TMCA. These data support the further investigation of TMCA as a GABAA/BZ receptor agonist for anti-seizure therapy.