bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/519322

Behavioural Evaluation of the Anticonvulsant Properties of the Traditional Medicine Anonna Senegalensis on Parabss Drosophila melanogaster Mutants.

Dare, S.·Merlo, E.·Ekanem, P. E.·Berni, J.
View original source ↗Export metadata ↓

Abstract

Epilepsy is the most common serious neurological disorder affecting 50 million people worldwide, 40 millions of which live in developing countries. Despite the introduction of a dozen of new Anti-Epileptic Drugs (AEDs), one third of the patients continue to have seizure regardless of receiving a AEDs treatment. This emphasize on the need to discover new drugs with different mechanisms of action. Traditional medicine (TM), pays a significant role in the treatment of epilepsy in many countries and offers an affordable and accessible alternative to AEDs. However, the lack of both empirical testing in animal models and clinical data places constrains to their clinical recommendation.\n\nIn this study, we use Drosophila melanogaster as a model for epilepsy and tested the anti-seizure effect of leaf and stem bark aqueous extract form Annona senegalensis, a plant used as anti-convulsant by rural populations in Africa.\n\nOur results show, that at the concentrations tested, the leaf extract of A. senegalensis was more effective than the AEDs phenytoin and phenobarbital to control seizures. These promising results demonstrate that Drosophila is an excellent model for new drug discovery and that it could be used to do large scale screening of TMs for the treatment of epilepsy.

Explore related subjects

pharmacology and toxicologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Dare, S., Merlo, E., Ekanem, P. E., Berni, J.. 2019-01-13. Behavioural Evaluation of the Anticonvulsant Properties of the Traditional Medicine Anonna Senegalensis on Parabss Drosophila melanogaster Mutants.. https://doi.org/10.1101/519322

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Lipid-ASO therapeutics exhibit differential tissue targeted delivery upon systemic or local CNS administration

Antisense oligonucleotides (ASOs) are a powerful therapeutic modality, but their full potential is hindered by pharmacokinetic properties that affect tissue and cellular delivery. Lipid conjugation is increasingly used to modulate ASO's biodistribution and promote extrahepatic activity, yet lipid dependent effects on in vivo functional delivery, particularly in the central nervous system (CNS), remain less explored. Here, we performed a side by side in vivo comparison of cholesterol, palmitic acid (C16:0), docosanoic acid (C22:0), and eicosapentaenoic acid (C20:5) conjugated to a fully phosphorothioated 3 10 3 LNA gapmer ASO targeting the Malat1 long non coding RNA. Lipid-ASO conjugates were administered systemically or locally in the brain of mice and evaluated for tissue level and cellular level distribution by imaging, qPCR and single-cell RNA sequencing, simultaneously annotating cell origin and global transcriptional changes within the cell. Following systemic administration in mice, lipid conjugation improved overall multi organ efficacy compared to unconjugated ASO, but with pronounced tissue specific differences. Single cell sequencing of liver and heart transcriptomes revealed lipid dependent cellular uptake patterns and transcriptional responses distinct from administration of unconjugated ASO. After intracerebroventricular administration, selected fatty acid conjugates enhanced silencing in deep brain regions such as the striatum, whereas cholesterol conjugation impaired functional delivery despite increased CNS retention. Light-sheet microscopy showed restricted parenchymal penetration of cholesterol ASOs compared with broader but heterogeneous distribution of palmitic acid conjugate. Together, these findings demonstrate that lipid identity critically determines ASO efficacy, productive cellular uptake, and regional CNS engagement, emphasizing the need for context specific lipid design in ASO therapeutic development.

pharmacology and toxicology↗
bioRxiv2026

Novel Dissymmetric Ionizable Lipid-Assembled Lipid Nanoparticles for Delivery of Ferroptosis-Related siRNA in Diabetic Treatment

Small interfering RNA (siRNA) enables precise post-transcriptional gene silencing for refractory diseases, yet its clinical translation remains limited by the lack of safe and efficient delivery vectors. Inspired by the dissymmetric alkyl chain architecture of natural membrane phospholipids, we designed and synthesized 34 novel ionizable lipids with dissymmetric hydrophobic tails and formulated them into lipid nanoparticles (LNPs). Through systematic physicochemical and biological assessments, we established clear structure-activity relationships and identified two lead LNPs (O14-LNP, H18a-LNP) with superior endosomal escape capacity, enhanced in vivo gene silencing potency, and favorable biosafety relative to the clinical benchmark MC3-LNP. In both streptozotocin-induced and spontaneous db/db type 2 diabetes (T2D) mouse models, lead LNPs delivering ferroptosis-related siRNAs effectively ameliorated glucose and lipid metabolic disorders, restored islet function, and alleviated hepatic steatosis. This study not only lays a theoretical foundation for the rational design of novel ionizable lipids, but also validates the therapeutic potential of siRNA therapy targeting ferroptosis, providing a versatile delivery platform and targeted therapeutic strategy for the treatment of T2D.

pharmacology and toxicology↗
bioRxiv2019

A Data-Driven Transcriptional Taxonomy of Adipogenic Chemicals to Identify Emerging Metabolic Health Threats

BackgroundChemicals in disparate structural classes activate specific subsets of PPAR{gamma}s transcriptional programs to generate adipocytes with distinct phenotypes. ObjectivesOur objectives were to 1) establish a novel classification method to predict PPAR{gamma} ligands and modifying chemicals, and 2) create a taxonomy to group chemicals based on their effects on PPAR{gamma}s transcriptome and downstream metabolic functions. We tested the hypothesis that environmental adipogens highly ranked by the taxonomy, but segregated from therapeutic PPAR{gamma} ligands, would induce white but not brite adipogenesis. Methods3T3-L1 cells were differentiated in the presence of 76 chemicals (negative controls, nuclear receptor ligands known to influence adipocyte biology, potential environmental PPAR{gamma} ligands). Differentiation was assessed by measuring lipid accumulation. mRNA expression was determined by RNA-Seq and validated by RT-qPCR. A novel classification model was developed using an amended random forest procedure. A subset of environmental contaminants identified as strong PPAR{gamma} agonists were analyzed by their effects on lipid handling, mitochondrial biogenesis and cellular respiration in 3T3-L1 cells and human preadipocytes. ResultsWe used lipid accumulation and RNA sequencing data to develop a classification system that 1) identified PPAR{gamma} agonists, and 2) sorted chemicals into likely white or brite adipogens. Expression of Cidec was the most efficacious indicator of strong PPAR{gamma} activation. Two known environmental PPAR{gamma} ligands, tetrabromobisphenol A and triphenyl phosphate, which sorted distinctly from therapeutic ligands, induced white adipocyte genes but failed to induce Pgc1a and Ucp1, and induced fatty acid uptake but not mitochondrial biogenesis in 3T3-L1 cells. Moreover, two chemicals identified as highly ranked PPAR{gamma} agonists, tonalide and quinoxyfen, induced white adipogenesis without the concomitant health-promoting characteristics of brite adipocytes in mouse and human preadipocytes. DiscussionA novel classification procedure accurately identified environmental chemicals as PPAR{gamma} ligands distinct from known PPAR{gamma}-activating therapeutics. The computational and experimental framework has general applicability to the classification of as-yet uncharacterized chemicals.

pharmacology and toxicology↗