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

Relwendé Justin Ouédraogo; Muhammad Jamal; Lassina Ouattara; Muhammad Nadeem-Ul-Haque; Faisal Khan; Shabana Usman Sımjee; Georges Anicet Ouédraogo; Farzana Shaheen

doi:10.4274/tjps.galenos.2023.14704

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

Turk J Pharm Sci. 2024 May 14;21(2):104-112. doi: 10.4274/tjps.galenos.2023.14704.

Authors

Relwendé Justin Ouédraogo^{1

2}, Muhammad Jamal³, Lassina Ouattara^{1

2}, Muhammad Nadeem-Ul-Haque³, Faisal Khan³, Shabana Usman Sımjee³, Georges Anicet Ouédraogo^{1

2}, Farzana Shaheen³

Affiliations

¹ Nazi Boni University, Department of Biological Sciences, Life and Earth Sciences Training and Research Unit, Bobo-Dioulasso, Burkina Faso.
² Nazi Boni University, Animal Health and Biotechnology Research and Teaching Laboratory, Bobo-Dioulasso, Burkina Faso.
³ Karachi University, Third World Center for Science and Technology, Hussain Ebrahim Jamal Research Institute of Chemistry, Karachi, Pakistan.

Abstract

Objective: This study aimed to investigate whether Mitragyna inermis (Willd.) Otto Kuntze organic and aqueous extracts are able to control seizures induced by pentylenetetrazol (PTZ) in mice based on flavonoid fingerprints and alkaloidal contents.

Materials and methods: Ethanolic extract and decoction-derived fractions from roots, leaves, and stems were subjected to chromatographic fingerprinting using AlCl₃ and screening for their antiseizure effects using PTZ-induced acute seizure model. From the fractions that showed potent bioactivities, plausible antiseizure alkaloids were isolated using thin layer chromatography, and their structures were elucidated using ¹H NMR, 2D NMR, ¹³C NMR, and FAB-HR (+ve or -ve).

Results: All fractions, with the exception of the dichloromethane and hexane fractions, revealed remarkable flavonoid fingerprints. An acute PTZ-induced seizure test revealed that ethanolic extract of stem bark [500 mg/kg body weight (bw)], ethyl acetate extract of stem bark (500 mg/kg bw), and aqueous extract of leaves (300 mg/kg bw) significantly delayed the occurrence of hind limb tonic extension (HLTE); however, a non-significant delay was observed in the onset of first myoclonic jerk compared with control animals. Isolation yielded four main alkaloids: that are, pteropodine (1), isopteropodine (2), mitraphylline (3) and corynoxeine (4). Corynoxeine is a new compound derived from M. inermis.

Conclusion: This study suggests that flavonoid fingerprints are tracers of M. inermis anticonvulsant ingredients. The stem bark ethanolic and ethyl acetate extracts and leaf aqueous extracts contain anticonvulsant bioactive principles that delay notifying the HLTE occurring in male naval medical research institute mice. Furthermore, alkaloidal contents also remain 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 promising antiseizure agents derived from M. inermis in experimental animals.

Keywords: Mitragyna inermis; alkaloids; antiseptics; corynoxeine; flavonoids.