Biflavonoids from Ochna Schweinfurthiana Restore Rotenone Toxicity in Drosophila Melanogaster: Implications for Parkinson's Disease
Cyrille Aubin Kuetche Feussi
Department of Biochemistry, University of Yaoundé, Cameroon.
Brice Ayissi Owona *
Faculty of Science, Laboratory of Pharmacology and Toxicology, Yaoundé, Cameroon.
Viviane Ngoungoure Ndam
Faculty of Science, Laboratory of Pharmacology and Toxicology, Yaoundé, Cameroon.
Nicolas Angélique Messi
Department of Organic Chemistry, University of Yaoundé, Cameroon.
Nico. F Njayou
Faculty of Science, Laboratory of natural substances, Yaoundé, Cameroon.
Paul F Moundipa
Faculty of Science, Laboratory of natural substances, Yaoundé, Cameroon.
*Author to whom correspondence should be addressed.
Abstract
Nowadays, neurodegenerative diseases represent a major health problem worldwide, with Parkinson's disease being the second most common neurodegenerative disease after Alzheimer's disease. Medical research has led to the development of a large number of drugs and palliative therapies; however, they have not succeeded in curing or halting the progression of the disease, have numerous side-effects and are subject to a loss of efficacy over time.
The aim of this study was to evaluate the effects of 3 biflavonoids on key targets involved in the pathophysiological process of rotenone-induced PD, using Drosophila melanogaster as an animal model. In silico molecular docking analysis was carried out using Molegro virtual Docker software between pathological PD targets (alpha-synuclein, acetylcholine esterase, super oxide dismutase, nitric oxide synthase, catalase) and the 3 biflavonoids. The toxicity of the biflavonoids was then assessed to determine the appropriate treatment dose for Drosophila exposed to 250/500 µM rotenone for 7 days. Motor activity was assessed by negative geotaxis and open field assays; oxidative stress markers and acetylcholinesterase activity were also assayed.
The 3 biflavonoids OB3B, OE1 and OSF3/EF1 (Isochamaejasmin, Chamaejasmin, and Amentoflavone) all obtained excellent interaction scores with the pathological targets; showing significant activity (p < 0.001) by increasing GSH levels and reducing MDA and NO levels, with an increase in acetylcholinesterase activity and a restoration of the balance of activity between SOD and catalase. Finally, OSF3/EF1 proved to be the best of the 3 biflavonoids studied. These observations position these molecules as potential candidates for the formulation of more effective lead drug candidates for PD treatment.
Keywords: Parkinson's disease, bioflavonoids, rotenone, Drosophila melanogaster, in silico