Zintegrowana ocena komputerowa i doświadczalna potencjału przeciwpadaczkowego rośliny Chenopodium album L. w modelu napadów indukowanych pentylenetrazołem
Integrated In Silico and In Vivo Evaluation of the Antiepileptic Potential of Chenopodium album L. in a Pentylenetetrazole-Induced Seizure Model
W skrócie
[Preprint - wstępne wyniki] Badacze przeanalizowali ekstraktę z rośliny Chenopodium album (pokrzywa kanadyjska) i znaleźli w niej 27 substancji, które mogą pomagać w epilepsji. Komputerowe modelowanie wykazało, że głównym mechanizmem działania jest wpływ na białko STAT3 odpowiedzialne za zapalenie w mózgu. Testy na myszach potwierdziły, że ekstrakta zmniejsza napady padaczkowe w sposób zależny od dawki, a w najwyższej dawce (400 mg/kg) działa podobnie jak konwencjonalny lek - etosukcymid.
Oryginalny abstract (angielski)
Abstract Background Epilepsy is a multifactorial disorder of the central nervous system characterized by recurrent, unprovoked seizures resulting from abnormal neuronal activity. Despite available antiepileptic drugs, treatment is limited by drug resistance and adverse effects, highlighting the need for safer agents. This study investigated the anticonvulsant potential of Chenopodium album L. using an integrated computational and experimental approach. Methods Methanolic leaf extract of Chenopodium album was analysed by LC–MS to identify phytoconstituents. Network pharmacology, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, molecular docking, molecular dynamics simulation, MM-GBSA, principal component analysis (PCA), free energy landscape (FEL), and ADMET prediction were performed. Anticonvulsant activity was validated in the pentylenetetrazole (PTZ)-induced seizure model in mice. Results LC–MS identified 27 phytoconstituents. Network pharmacology revealed 541 overlapping targets between C. album phytoconstituents and epilepsy-related genes, with STAT3 as the key hub protein. Enrichment analysis highlighted EGFR tyrosine kinase inhibitor resistance, JAK–STAT, HIF-1, and estrogen signalling pathways. Quercetin showed the highest affinity for STAT3, while molecular dynamics, MM-GBSA, PCA, and FEL analyses confirmed a stable quercetin–STAT3 complex. ADMET prediction indicated favorable pharmacokinetic properties. The in vivo anticonvulsant activity of the methanolic leaf extract was confirmed in the pentylenetetrazole-induced seizure model, where treatment significantly delayed seizure onset and reduced seizure duration in a dose-dependent manner, with complete seizure protection observed at 400 mg/kg, comparable to ethosuximide. Conclusions Chenopodium album exhibited significant anticonvulsant activity by modulating multiple molecular targets, particularly STAT3, supporting its potential as multi-target therapeutic candidate for epilepsy.