Propensity of Selaginella delicatula aqueous extract to offset rotenone-induced oxidative dysfunctions and neurotoxicity in Drosophila melanogaster: Implications for Parkinson's disease.

The primary objective of this investigation was to examine the neuroprotective efficacy of an aqueous extract of Selaginella delicatula (a pteridophyte) employing a rotenone (ROT) Drosophila model in vivo. Aqueous extract of S. delicatula (SDAE) exhibited multiple antioxidant activity in selected chemical systems. Initially, we examined the ability of SDAE-enriched diet to modulate the levels of endogenous oxidative markers and antioxidant defenses in Drosophila melanogaster. Further, employing a co-exposure paradigm, we investigated the propensity of SDAE to protect flies against ROT-induced lethality, locomotor dysfunction, oxidative stress, mitochondrial dysfunctions and neurotoxicity. Adult flies were fed SDAE-enriched diet (0.05, 0.1 and 0.2%) with or without ROT (500 μM) for seven consecutive days. SDAE offered concentration-dependent protection against ROT-induced lethality (30-95% protection), while the survivor flies performed better in the negative geotaxis assay suggesting attenuation of ROT-induced locomotor deficits. Biochemical analysis revealed that SDAE completely restored ROT-induced elevation in the levels of ROS, protein carbonyls and hydroperoxides in both head and body regions of flies. Elevations in the activities of antioxidant enzymes (superoxide dismutase, glutathione reductase) and glutathione-S-transferase caused by ROT were also restored to normal levels by SDAE. Further, SDAE improved the activity levels of membrane bound enzymes viz., NADH-cytochrome c reductase and succinate dehydrogenase suggesting its propensity to protect mitochondrial integrity. Interestingly, SDAE normalized the activity levels of acetylcholinesterase and ROT-induced dopamine depletion. Collectively, these findings suggest the neuromodulatory potential of SDAE and our further studies are directed toward characterization of the nature of biomolecule/s and their mechanism of action employing relevant cell models.

Girish C ，Muralidhara 《-》

Neuroprotective effect of aqueous extract of Selaginella delicatula as evidenced by abrogation of rotenone-induced motor deficits, oxidative dysfunctions, and neurotoxicity in mice.

Chandran G ，Muralidhara 《-》

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 (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 oxidative stress mediated neurodegenerative conditions.

Rao SV ，Muralidhara ，Yenisetti SC ，Rajini PS ... -  《-》

Neuroprotective efficacy of Bacopa monnieri against rotenone induced oxidative stress and neurotoxicity in Drosophila melanogaster.

Hosamani R ，Muralidhara 《-》

Valeriana officinalis attenuates the rotenone-induced toxicity in Drosophila melanogaster.

In this study, we investigated the potential protective effects of Valeriana officinalis (V. officinalis) against the toxicity induced by rotenone in Drosophila melanogaster (D. melanogaster). Adult wild-type flies were concomitantly exposed to rotenone (500 μM) and V. officinalis aqueous extract (10mg/mL) in the food during 7 days. Rotenone-fed flies had a worse performance in the negative geotaxis assay (i.e. climbing capability) and open-field test (i.e. mobility time) as well as a higher incidence of mortality when compared to control group. V. officinalis treatment offered protection against these detrimental effects of rotenone. In contrast, the decreased number of crossings observed in the flies exposed to rotenone was not modified by V. officinalis. Rotenone toxicity was also associated with a marked decrease on the total-thiol content in the homogenates and cell viability of flies, which were reduced by V. officinalis treatment. Indeed, rotenone exposure caused a significant increase in the mRNA expression of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) and also in the tyrosine hydroxylase (TH) gene. The expression of SOD and CAT mRNAs was normalized by V. officinalis treatment. Our results suggest that V. officinalis extract was effective in reducing the toxicity induced by rotenone in D. melanogaster as well as confirm the utility of this model to investigate potential therapeutic strategies on movement disorders, including Parkinson disease (PD).

Sudati JH ，Vieira FA ，Pavin SS ，Dias GR ，Seeger RL ，Golombieski R ，Athayde ML ，Soares FA ，Rocha JB ，Barbosa NV ... -  《-》