PUBLICATION
Anti-seizure activity of African medicinal plants: the identification of bioactive alkaloids from the stem bark of Rauvolfia caffra using an in vivo zebrafish model
- Authors
- Chipiti, T., Viljoen, A.M., Cordero-Maldonado, M.L., Veale, C.G.L., Van Heerden, F.R., Sandasi, M., Chen, W., Crawford, A.D., Enslin, G.M.
- ID
- ZDB-PUB-210613-6
- Date
- 2021
- Source
- Journal of ethnopharmacology 279: 114282 (Journal)
- Registered Authors
- Cordero-Maldonado, Maria Lorena
- Keywords
- Epilepsy, Pleiocarpamine, Rauverine H, Rauvolfia caffra, Zebrafish
- MeSH Terms
-
- Alkaloids/isolation & purification
- Alkaloids/pharmacology*
- Animals
- Anticonvulsants/isolation & purification
- Anticonvulsants/pharmacology*
- Disease Models, Animal
- Epilepsy/drug therapy*
- Female
- High-Throughput Screening Assays
- Larva
- Male
- Medicine, African Traditional
- Plant Extracts/isolation & purification
- Plant Extracts/pharmacology*
- Plants, Medicinal/chemistry
- Rauwolfia/chemistry*
- Seizures/drug therapy
- South Africa
- Zebrafish
- PubMed
- 34118342 Full text @ J. Ethnopharmacol.
Citation
Chipiti, T., Viljoen, A.M., Cordero-Maldonado, M.L., Veale, C.G.L., Van Heerden, F.R., Sandasi, M., Chen, W., Crawford, A.D., Enslin, G.M. (2021) Anti-seizure activity of African medicinal plants: the identification of bioactive alkaloids from the stem bark of Rauvolfia caffra using an in vivo zebrafish model. Journal of ethnopharmacology. 279:114282.
Abstract
Ethnopharmacological relevance Epilepsy is one of the major chronic diseases that does not have a cure to date. Adverse drug reactions have been reported from the use of available antiepileptic drugs (AEDs) which are also effective in only two-thirds of the patients. Accordingly, the identification of scaffolds with promising anti-seizure activity remains an important first step towards the development of new anti-epileptic therapies, with improved efficacy and reduced adverse effects. Herbal medicines are widely used in developing countries, including in the treatment of epilepsy but with little scientific evidence to validate this use. In the search for new epilepsy treatment options, the zebrafish has emerged as a chemoconvulsant-based model for epilepsy, mainly because of the many advantages that zebrafish larvae offer making them highly suitable for high-throughput drug screening.
Aim of the study In this study, 20 medicinal plants traditionally used in South Africa to treat epilepsy were screened for antiepileptic activity using a zebrafish larvae model.
Materials and methods Toxicity triaging was conducted on 120 crude extracts, 44 fractions and three isolated compounds to determine the maximum tolerated concentration (MTC) of each extract, fraction or compound. MTC values were used to guide the concentration range selection in bioactivity studies. The effectiveness of crude extracts, fractions and isolated compounds from Rauvolfia caffra Sond. in suppression of pentylenetetrazole (PTZ) induced seizure-like behaviour in a 6-dpf zebrafish larvae model was measured using the PTZ assay.
Results Following a preliminary toxicity triage and bioactivity screen of crude extracts from 20 African plants used traditionally for the treatment and management of epilepsy, the methanolic extract of Rauvolfia caffra Sond. was identified as the most promising at suppressing PTZ induced seizure-like behaviour in a zebrafish larvae model. Subsequent bioactivity-guided fractionation and spectroscopic structural elucidation resulted in the isolation and identification of two tryptoline derivatives; a previously unreported alkaloid to which we assigned the trivial name rauverine H (1) and the known alkaloid pleiocarpamine (2). Pleiocarpamine was found to reduce PTZ-induced seizures in a dose-dependent manner.
Conclusions Accordingly, pleiocarpamine represents a promising scaffold for the development of new anti-seizure therapeutic compounds. Furthermore, the results of this study provide preliminary evidence to support the traditional use of Rauvolfia caffra Sond. in the treatment and management of epilepsy. These findings warrant further studies on the antiepileptic potential of Rauvolfia caffra Sond. using other models.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping