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

• Published in: Neurotoxicology (Park Forest South) 2016-01, Vol.52, p.230-242
• Main Authors: Rao, Sriranjini Venkat, Muralidhara, Yenisetti, Sarat Chandra, Rajini, Padmanabhan S.
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase - metabolism; Animals; Antioxidants - metabolism; Biomarkers - metabolism; Carotenoids - pharmacology; Crocin; Crocus - chemistry; Crocus sativus; Disease Models, Animal; Dopamine - metabolism; Drosophila; Drosophila melanogaster - drug effects; Glutathione - metabolism; Hydrogen Peroxide - metabolism; Locomotion - drug effects; Longevity - drug effects; Mitochondria - drug effects; Mitochondria - metabolism; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Neurotoxicity; Nitric Oxide - metabolism; Oxidative stress; Oxidative Stress - drug effects; Paraquat - antagonists & inhibitors; Paraquat - toxicity; Parkinsonian Disorders - diet therapy; Parkinsonian Disorders - drug therapy; Parkinsonian Disorders - metabolism; Parkinsonism; Phytotherapy; Plant Extracts - pharmacology; Protein Carbonylation - drug effects; Reactive Oxygen Species - metabolism; Rotenone; Sulfhydryl Compounds - metabolism
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2015.12.010

•Saffron extract/crocin significantly reduced rotenone induced mortality, rescued locomotor phenotype, diminished oxidative stress in flies.•Rotenone-induced mitochondrial dysfunctions were markedly attenuated by SME/CR enrichment.•Saffron extract/crocin enrichment delayed the onset of locomotor deficits and extended life span in rotenone-stressed flies.•Flies provided with SME/CR prophylaxis exhibited marked resistance to an acute Paraquat challenge. 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 (500μM) 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 (50μM)-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 o