Cholinergic Inhibition and Antioxidant Potential of Gongronema latifolium Benth Leaf in Neurodegeneration: Experimental and In Silico Study.

Autor: Gyebi GA; Department of Biochemistry, Bingham University, Karu, Nigeria. gideonagyebi@gmail.com.; Department of Biotechnology and Food Science, Durban University of Technology, Durban, 4000, South Africa. gideonagyebi@gmail.com., Ejoh JC; Department of Biochemistry, Bingham University, Karu, Nigeria., Ogunyemi OM; Nutritional and Industrial Biochemistry Research Unit, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, 200005, Nigeria., Afolabi SO; Department of Pharmacology and Therapeutics, University of Ilorin, Ilorin, Nigeria., Ibrahim IM; Department of Biophysics, Cairo University, Giza, Egypt., Anyanwu GO; Department of Biochemistry, Bingham University, Karu, Nigeria., Olorundare OE; Department of Pharmacology and Therapeutics, University of Ilorin, Ilorin, Nigeria., Adebayo JO; Department of Biochemistry, University of Ilorin, Ilorin, Nigeria., Koketsu M; Department of Chemistry and Biomolecular Science, Gifu University, Gifu, Japan.
Jazyk: angličtina
Zdroj: Cell biochemistry and biophysics [Cell Biochem Biophys] 2024 Aug 09. Date of Electronic Publication: 2024 Aug 09.
DOI: 10.1007/s12013-024-01467-7
Abstrakt: The use of Gongronema latifolium for the management of various forms of neurological disorders has generated a lot of interest in the need to further investigate its neurotherapeutic constituents. This work, therefore, focused on assessing the inhibitory potential of selected bioactive components derived from G. latifolium against key neurotherapeutic targets and oxidant species associated with neurodegeneration using in vitro analysis and biomolecular modelling. G. latifolium methanol extract (GLME), solvent partition, chromatographic fractions (A-F) of GLME and pregnane compounds (Iloneoside and marsectohexol) derived from fraction-B with the highest activity were investigated for in vitro acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and monoamine oxidase (MAO) inhibition in addition to their in vitro antioxidant activities. The interactions of iloneoside, marsectohexol, and reference drugs with human acetylcholinesterase, butyrylcholinesterase, and β-secretase (BACE-1) were further assessed using molecular docking, binding free energy calculations, cluster analysis, and molecular dynamics simulations. The GLME and fractions inhibited the activities of both acetylcholinesterase and butyrylcholinesterase in a dose-dependent manner. Iloneoside and marsectohexol exhibited in vitro concentration-dependent inhibitory activities against acetylcholinesterase (IC50 = 19.28, 184.9 µM, respectively) and butyrylcholinesterase (IC50 = 30.75, 43.4 µM, respectively). These compounds also possess ferric ion-reducing, hydroxyl, and superoxide radical-scavenging activities. Iloneoside had the highest docking scores of -9.8, -9.9 -9.4 Kcal for AChE, BChE, and BACE1, respectively. The stability of the interaction of the bioactive compounds with the catalytic residues of the protein targets was preserved in a 100 ns molecular dynamics simulation. Iloneoside, a rare pregnane glycoside, was identified as a neurotherapeutic constituent of G. latifolium leaf. Further studies are suggested to investigate the neurotherapeutic potential in animal models.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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