Involvement of GABA/BDZ receptors in the anticonvulsant effects of dihydrosanguinarine from Bocconia arborea S. Watson.

Abstract

Bocconia arborea S. Watson (B. arborea) belongs to the Papaveraceae family and is used in folk medicine because of its depressant effect on the central nervous system. However, its benefits on cerebral paroxysmal activity as an anticonvulsant treatment remain unknown. This study aimed to evaluate the anticonvulsant effect of B. arborea and one of its abundant isolated metabolites dihydrosanguinarine (DHS) by means of experimental models of seizures in mice simultaneously to an electrocorticographic (ECoG) analysis. B. arborea was prepared as extracts with different polarity using hexane (HEX), dichloromethane (DCM), and methanol (MeOH) solvents to choose the most active one and to identify and isolate a bioactive metabolite. DHS was purified from the HEX extract. The anticonvulsant activity was evaluated with each extract giving an intraperitoneal (i.p.) administration of 100 mg/kg, and 30 min after, seizure behavior was induced by the pentylenetetrazole (PTZ, 85 mg/kg, i.p.) or maximal electroshock stimulation (MES) tests in mice. Molecular docking analysis was performance to reinforce the possible mechanism of action. Our results of seizure behavior and ECoG analysis showed that the HEX extract significantly (p < 0.0001) delayed the onset of seizures and decreased the incidence (p < 0.005) with lower mortality rate (p < 0.05), where DHS was partially responsible for this activity with a possible GABAergic mechanism of action involving the BDZ allosteric site. The MeOH extract also produced a significant effect (p < 0.05) but with less intensity than the HEX extract in the PTZ-induced seizures. A similar anticonvulsant response was observed in the MES test in the presence of DHS (p < 0.005) and the HEX extract (p < 0.05), but not in the case of the MeOH extract. In conclusion, our study provides evidence that non-polar and polar constituents of B. arborea participate in its anticonvulsant property, where DHS might play an important role in the therapy of convulsions mediated by GABA_A/BDZ receptor modulation.