Biflavonoids from Ochna Schweinfurthiana Restore Rotenone Toxicity in Drosophila Melanogaster: Implications for Parkinson's Disease

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.