Pharmacological Evaluation of Anticonvulsant and Anxiolytic Effects of Mitragyna speciosa Leaf Alkaloid-Enriched Fraction through Experimental and Computational Studies
TL;DR
Findings indicate that AEMS possesses significant anticonvulsant and anxiolytic activity and may be useful in managing convulsions and anxiety.
Abstract
The present study aimed to evaluate the anticonvulsant and anxiolytic potential of the alkaloid-enriched leaf fraction of Mitragyna speciosa (AEMS) using experimental and computational approaches. Powdered leaves were extracted by Stas-Otto method to obtain the alkaloid-enriched fraction, followed by LC-MS and preliminary phytochemical analysis using standard methods. AEMS was administered at doses of 50 mg/kg and 100 mg/kg and its effects were assessed using in vivo models over 15 days. Statistical analysis was performed using one-way ANOVA followed by Dunnett’s test. In vitro antioxidant assays and in silico molecular docking studies were conducted to evaluate interactions with the GABAA -BZD receptor. LC-MS and phytochemical screening confirmed the presence of alkaloids, viz. mitragynine, 7-hydroxymitragynine and corynoxine B. AEMS demonstrated significant (*p < 0.05) anticonvulsant and anxiolytic activities, with the 50 mg/kg dose exhibiting greater efficacy. The antioxidant activity was reported to be comparatively lesser (IC50 = 399.93 ± 1.35 µg/mL) than the ascorbic acid standard (IC50 = 49.6 ± 6.55 µg/mL) by DPPH method. Docking studies revealed strong binding affinities for all the three compounds wherein, 7-hydroxymitragynine demonstrated profound binding affinity (-7.7 kcal/mol), comparable to diazepam (-8.8 kcal/mol), suggesting GABAergic involvement. These findings indicate that AEMS possesses significant anticonvulsant and anxiolytic activity and may be useful in managing convulsions and anxiety.