Evidence of neuroprotective effects of saffron and crocin in a Drosophila model of parkinsonism

Evidence suggests that saffron and its major bioactives exhibit significant neuromodulatory effects in
various animal models. However, specific data related to their efficacy to attenuate oxidative stress and
neurotoxicity in animal models of Parkinson’s disease (PD) are limited. Hence, we investigated the
neuroprotective efficacy of saffron methanolic extract (SME) and its active constituent, crocin (CR)
employing a Drosophila model of parkinsonism. We focussed on attenuation of Rotenone (ROT)-induced
locomotor phenotype, oxidative stress, mitochondrial dysfunction and neurotoxicity in this model. SME
and CR-enrichment significantly reduced ROT (500 mM) induced mortality, rescued the locomotor
phenotype and diminished the enhanced levels of oxidative stress markers in head/body regions of
flies.
The reduced levels of reduced glutathione (GSH) and total thiols (TSH) resulting from ROT exposure were
significantly restored with concomitant enhancement of the antioxidant enzymes activities. Further,
ROT-induced mitochondrial dysfunctions (MTT reduction, activities of SDH and NADH-Cyt C reductase
(complexes I–III) enzymes) were markedly attenuated by SME/CR enrichment. While ROT elevated the
activity of acetylcholinesterase (AChE) in head/body regions, both the treatments caused marked
diminution of AChE activity and restored the dopamine levels suggesting their effectiveness to mitigate
cholinergic function. Interestingly, SME/CR enrichment significantly delayed the onset of locomotor
deficits and extended life span of
flies among ROT (50 mM)-stressed
flies. In a satellite study,
flies
provided with SME/CR prophylaxis exhibited marked resistance to an acute Paraquat (PQ) challenge as
evidenced by the lower incidence of lethality and improved locomotor phenotype. Taken together, the
neuroprotective effects of saffron and crocin in the
fly model may be largely attributable to its antioxidant
action. Based on our
findings, we propose that saffron may be exploited as a supplementary therapeutic
agent in PD and other oxidative stress mediated neurodegenerative conditions.