Probable mechanisms involved in the antiepileptic activity of Clerodendrum polycephalum Baker (Labiatae) leaf extract in mice exposed to chemical‐induced seizures

The leaves of Clerodendrum polycephalum Baker (Labiatae) are used as a dietary legume supplement and applied ethnomedicinally for the management of epilepsy, convulsion, and spasms. This study is aimed at evaluating the effects of Clerodendrum polycephalum (CP) leaf extract on chemical-induced seizures in mice and the possible mechanisms of action. Swiss albino mice were pretreated with CP (50, 100, or 500 mg/kg, p.o.) prior to intraperitoneal injection of picrotoxin (PTX) or pentylenetetrazole (PTZ). However, the most effective dose was used to elucidate the role of GABAergic and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling mechanisms in mice brains. Accordingly, we evaluated the preventive and reversal effects of CP on kainic acid (KA)-induced temporal lobe epilepsy (TLE), oxidative stress, and neuroinflammatory in mice. The pretreatment of mice with CP delayed the latencies to PTX and PTZ-induced seizures and decrement in the period of tonic-clonic attacks. Interestingly, CP (100 mg/kg) completely prevented PTZ-induced tonic-clonic seizures. Contrastingly, flumazenil (benzodiazepine receptor antagonist), N-G-nitro-L-Arginine (L-NNA) (10 mg/kg., neuronal nitric oxide synthase inhibitor), and methylene blue (MB) (2 mg/kg, a soluble guanylyl cyclase inhibitor) but not L-arginine (150 mg/kg., nitric oxide precursor) reversed CP-induced anticonvulsant-like effect in PTZ model. Furthermore, KA-elicited TLE was prevented by CP treatment. CP also attenuated KA-induced oxidative stress, cyooxygenase-2 (COX-2), and nuclear factor kappa-B (NF-kappa B) elevated expressions in the hippocampus. The study revealed that the ethanolic leaf extract of CP produced anticonvulsant actions through enhancement of antioxidant defense, GABAergic, and NO-cGMP signaling pathways as well as attenuation of inflammatory processes. Practical applications The leaves of Clerodendrum polycephalum Baker (Labiatae) are used as a dietary legume supplement and applied ethnomedicinally for the management of epilepsy, convulsion, and spasms. For this reason, we believe that supplementation of the Clerodendrum polycephalum leaf extract would prevent epileptic-related disorders in mice induced with epileptic conditions using kainic acid and other behavioral phenotypic models. Here, our findings clearly revealed that Clerodendrum polycephalum leaf extract protects against conditions of epileptic-related disorders and thus might be relevant as a dietary supplement in the prevention or delay of the onset of seizures and epileptic behavior.