Organoruthenium(II) Complexes Ameliorates Oxidative Stress and Impedes the Age Associated Deterioration in Caenorhabditis elegans through JNK-1/DAF-16 Signalling

Abstract

New ruthenium(II) complexes were synthesised and characterized by various spectro analytical techniques. The structure of the complexes 3 and 4 has been confirmed by X-ray crystallography. The complexes were subjected to study their anti-oxidant profile and were exhibited significantly greater in vitro DPPH radical scavenging activity than vitamin C. We found that complexes 1–4 confered tolerance to oxidative stress and extend the mean lifespan of mev-1 mutant worms and wild-type Caenorhabditis elegans. Further, mechanistic study and reporter gene expression analysis revealed that Ru(ƞ6-p-cymene) complexes maintained the intracellular redox status and offers stress resistance through activating JNK-1/DAF-16 signaling axis and possibly by other antioxidant response pathway. Notably, complex 3 and 4 ameliorates the polyQ (a Huntington’s disease associated protein) mediated proteotoxicity and related behavioural deficits in Huntington’s disease models of C. elegans. From these observations, we hope that new Ru(ƞ6-p-cymene) complexes could be further considered as a potential drug to retard aging and age-related neurodegenerative diseases.

α- and β-Santalols Delay Aging in Caenorhabditis elegans via Preventing Oxidative Stress and Protein Aggregation

“…Protein aggregation assay was performed using transgenic C. elegans strains expressing polyQ35::YFP (AM140) and polyQ40::YFP (AM141) fusion proteins in the body wall muscle cells as described. 33 In brief, age-sorted L1 larvae (30–40 individuals/treatment) were continuously exposed to santalol isomers at 20 °C for indicated time points. After that, the photomicrographs of control and treated worms were taken under a fluorescence microscope and scored for polyQ35::YFP and polyQ40::YFP aggregates across various adulthood stages.…”

East Indian sandalwood (Santalum album L.) oil confers neuroprotection and geroprotection inCaenorhabditis elegans viaactivating SKN-1/Nrf2 signaling pathway

“…The antioxidant activities of EISO and santalol isomers were measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical quenching experiment as described in our previous study. 32 Briefly, various concentrations of test compounds were added to 0.1 mM DPPH in methanol and the solution was vortexed vigorously. The tubes were then incubated for 20 min in the dark, and the absorbance was taken at 517 nm using UV-Vis spectrophotometer (UV-1800, Shimadzu, Japan).…”

“…A total of 25–30 randomly selected worms from each experiment were measured for GFP signal using ImageJ software (NIH, Bethesda, MD) by determining the mean pixel intensity and expressed as relative fluorescent unit (RFU). 32 …”

“…After incubation, photographic images were examined for ROS levels by quantifying the fluorescence intensity of DCF. 32 To analyze the CED-1 expression, transgenic strain MD701 has been used. Synchronized L3 stage worms were grown on the NGM plates in the presence or absence EISO, α- or β-santalol for 72 h at 20 °C with and without 6-OHDA treatment.…”

Reactive Species in Huntington Disease: Are They Really the Radicals You Want to Catch?

“…Aside from plant extracts, synthetic compounds like ruthenium (II) complexes were used to treat worms. These substances regulate stress response pathways through the JNK-1/DAF-16 signalling pathway [ 119 ]. Treating worms with this substance reduced polyQ aggregation in muscle cells, but showed less polyQ-mediated death of ASH neurons and improved chemosensory behaviour [ 119 ].…”