Attenuation of Dopaminergic Neuronal Dysfunction in Caenorhabditis elegans by Hydrophilic Form of Curcumin.

Curcumin (CUR), the principal curcuminoid and the “yellow coloring matter” of turmeric, has been demonstrated
to exhibit protective activity against various neurologic diseases. Owing to its hydrophobic in nature, CUR is
insoluble in water, and its poor solubility in aqueous solution remains a major barrier in its bioavailability and clinical
efficacy. In view of this, in the present study, we rendered the CUR hydrophilic by making an ‘inclusion compound’
with gamma cyclodextrin (γCD) and evaluated its neuroprotective efficacy by employing the model system
Caenorhabditis elegans. Both wild-type and transgenic strain of C. elegans [expressing green fluorescent protein
(GFP) specifically in the dopaminergic neurons [BZ555 (Pdat-1: GFP] were treated with either the well-known
neurotoxin, 6-hydroxydopamine (6-OHDA) or Monocrotophos (MCP), a neurotoxic insecticide. We examined the
ameliorative effect of CUR on phenotype (in terms of locomotion), reproductive parameters (brood size, egg-laying)
and longevity. Further, neurotoxicity was assessed by monitoring neurodegeneration of dopaminergic neurons and
acetylcholinesterase activity. We found that CUR treatment marginally increased egg laying, brood size and the
survival (by 3d). Interestingly, it also significantly decreased the dopaminergic neurodegeneration with a marginal
restoration of acetylcholinesterase activity among worms exposed to either OHDA or MCP. Our findings provide
evidence for the potential of CUR to ameliorate neuronal dysfunction in the worm model and suggest its use as a
therapeutic molecule against PD.