Antiseizure Activity of Mitragyna inermis in the Pentylenetetrazol (PTZ) -Induced Seizure Model in Mice: Involvement of Flavonoids and Alkaloids

Abstract

Ethnopharmacological relevance : Traditionally, Mitragyna inermis, is widely reported for its use in epilepsy management. Aim of the study : This study aimed to investigate if M. inermis organic and aqueous extracts are able to control seizures induced by pentylenetetrazol (PTZ) on mice based on flavonoid fingerprints and alkaloidal contains. Material and methods : Ethanolic extract and decoction-derived fractions from roots, leaves and stem were subjected to chromatographic fingerprinting using AlCl 3 and to the screening for their antiseizure effects using pentylenetetrazol (PTZ) -induced acute seizure model. From the fractions that showed potent bioactivities, the plausible antiseizure alkaloids were isolated by using thin layer chromatography and their structures were elucidated through 1 H NMR, 2D NMR, 13 C NMR and FAB-HR ( +ve or –ve ). Results: All fractions, with the exception of DCM and hexane fractions, revealed remarkable flavonoid fingerprints. Acute PTZ-induced seizure test shows that ethanolic extract of stem bark (500 mg/kg b.w.), ethyl acetate extract of stem bark (500 mg/kg b.w.) and aqueous extract of leaves (300 mg/kg b.w.) significantly delayed the occurrence of hind limb tonic extension (HLTE), however, non-significant delay was observed in the onset of first myoclonic jerk (FMJ) compared to control animals. Isolation yielded four main alkaloids that are, pteropodine ( 1 ), isopteropodine ( 2 ), mitraphylline ( 3 ) and corynoxeine ( 4 ). Corynoxeine is a new compound from M. inermis . Conclusion : This study suggests that flavonoid fingerprints are tracers of Mitragyna inermis anticonvulsant ingredients. Stem bark ethanolic and ethyl acetate extracts and leaf aqueous extracts contain anticonvulsant bioactive principles that delay notifying the hind limb tonic extension occurring in male NMRI mice. Furthermore, alkaloidal contains remain also the plausible bioactive anticonvulsant principles. All observations support the traditional use of M. inermis to manage epilepsy. However, further studies are needed to understand the effects of alkaloid fractions, flavonoids and the isolated compounds as a promising antiseizure agent derived from M. inermis in experimental animals.