GardeninA confers neuroprotection against environmental toxin in a Drosophila model of Parkinson’s disease

Abstract Parkinson’s disease is an age-associated neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons from midbrain. Epidemiological studies have implicated exposures to environmental toxins like herbicide paraquat as major contributors etiology in both mammalian and invertebrate models. We employed a paraquat-induced model Drosophila inexpensive vivo platform screen therapeutics natural products. identified polymethoxyflavonoid, GardeninA, with neuroprotective potential against parkinsonian symptoms involving reduced survival, mobility defects, neurons. GardeninA-mediated neuroprotection not solely dependent on its antioxidant activities but also involves modulation neuroinflammatory cellular death responses. Furthermore, we successfully shown GardeninA bioavailability fly heads after oral administration using ultra-performance liquid chromatography mass spectrometry. Our findings reveal molecular mechanistic insight into toxin-induced pathogenesis for novel therapeutic intervention.