Anti-Convulsant Activity of Soxhlet Leaf Extracts of Ajuga Integrifolia Buch.-Ham. Ex D.Don (Lamiaceae) in Mice

Abstract

Background

The leaves of Ajuga integrifolia Buch.-Ham. ex D.Don (Lamiaceae) have long been used as an anti-convulsant remedy in Ethiopian traditional medicine. However, the evidence supporting their use is sparse in the literature. This study was conducted to add to the existing body of knowledge about the anti-convulsant activity of the plant.

Methods

The anti-convulsant activity of the extract was investigated in both acute (pentylenetetrazol [PTZ], 80 mg/kg; and maximal electroshock [MES]) and chronic (PTZ, 35 mg/kg) kindling seizure models. For the experimental paradigms, various doses of the extract (100, 200, and 400 mg/kg) were administered. Positive controls received sodium valproate (200 mg/kg) for the PTZ model and phenytoin (25 mg/kg) for the MES model. Parameters including the onset of clonus and duration of hindlimb tonic extension were recorded and compared with controls. Moreover, the total alkaloid, flavonoid, and phenol contents of the extracts were determined.

Results

Ethyl acetate extract produced a superior effect among all solvent extracts in both the PTZ and MES models. At all doses, it significantly delayed the mean onset of clonus (p<0.01) in the PTZ test compared to controls. It also significantly reduced (p<0.001) the mean duration of hindlimb tonic extension in the MES model. Treatment of mice with 200 mg/kg (p<0.01) and 400 mg/kg (p<0.001) of ethyl acetate extract significantly protected against PTZ-induced kindling compared to controls. The leaf was found to contain 10.002±0.119 mg atropine equivalent per gram of dry extract of alkaloids, 9.045±0.8445 mg quercetin equivalent per gram of dry extract of flavonoids, and 21.928±1.118 mg gallic acid equivalent per gram of dry extract of phenols.

Conclusion

This study indicated that the plant A. integrifolia has anti-convulsant activity in both acute and chronic models of seizure. This plant represents a potential source for the development of a new anti-epileptic drug for pharmacoresistant epilepsy.

Keywords:

• Ajuga integrifolia
• anti-convulsant
• epilepsy
• kindling
• phytoconstituents
• seizure

Abbreviations

AED, anti-epileptic drug; GABA, gamma-aminobutyric acid; HLTE, hindlimb tonic extension; MES, maximal electroshock; PTZ, pentylenetetrazol.

Data Sharing Statement

The data sets used and/or analyzed during the current work are available and included in this article.

Ethics Approval and Informed Consent

The protocol was approved by the institutional review board of the School of Pharmacy, Addis Ababa University (reference no ERB/SOP/199/2019).

Acknowledgments

TD is grateful to Madda Walabu University and Addis Ababa University for granting him support during his studies. This paper was uploaded to the Addis Ababa University repository as a thesis in November 2021: http://etd.aau.edu.et/handle/123456789/32068.⁷² We express our heartfelt thanks to Addis Ababa University for providing financial support and all the necessary materials for the study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that there are no conflicts of interest regarding the publication of this paper.

Additional information

Funding

Financial support was provided by Addis Ababa University as part of an MSc research project.