title: Curcumin Monoglucoside Shows Improved Bioavailability and Mitigates Rotenone Induced Neurotoxicity in Cell and Drosophila Models of Parkinson's Disease.
abstract: Curcumin (CUR), a dietary polyphenol has diverse pharmacologic effects, but is limited by poor bioavailability. This is probably due to decreased solubility, cellular uptake and stability. In order to enhance its solubility and bioavailability, we synthesized the CUR bioconjugate curcumin monoglucoside (CMG) and tested its bioavailability, neuroprotective and anti-apoptotic propensity against rotenone (ROT) induced toxicity in N27 dopaminergic neuronal cells and Drosophila models. Our results elucidate that CMG showed improved bioavailability than CUR in N27 cells. Pre-treatment with CMG protected against ROT neurotoxicity and exerted antioxidant effects by replenishing cellular glutathione levels and significantly decreasing reactive species. CMG pre-treatment also restored mitochondrial complex I and IV activities inhibited by ROT. ROT-induced nuclear damage was also restored by CMG as confirmed by comet assay. CMG induced anti-apoptotic effects was substantiated by decreased phosporylation of JNK3 and c-jun, which in turn decreased the cleavage of pro-caspase 3. Q-PCR analysis of redox genes showed up-regulation of NOS2 and down-regulation of NQO1 upon ROT exposure and this was attenuated by CMG pre-treatment. Studies in the Drosophila ROT model revealed that, CMG administration showed better survival rate and locomotor activity, improved antioxidant activity and dopamine content than ROT treated group and was comparable with the CUR group. Based on these data, we surmise that CMG has improved bioavailability and offered neuroprotection comparable with CUR, against ROT-induced toxicity both in dopaminergic neuronal cell line and Drosophila models, with therapeutic implications for PD.
authors.affiliation: Department of Neurochemistry, National Institute of Mental Health and Neurosciences, No. 2900, Hosur Road, Bangalore, 560029, Karnataka, India.|Neurotoxicology Laboratory at the Neurobiology Research Center, National Institute of Mental Health and Neurosciences, No. 2900, Hosur Road, Bangalore, 560029, Karnataka, India.
authors.forename: M D
authors.initials: MD
authors.lastname: Pandareesh
authors.affiliation: Department of Chemistry, Centre of Bio-Medical Research (CBMR), Sanjay Gandhi Post Graduate Institute of Medical Sciences Campus, Raebareli Road, Lucknow, 226014, Uttar Pradesh, India.
authors.forename: M K
authors.initials: MK
authors.lastname: Shrivash
authors.affiliation: Department of Biochemistry, Jnana Sahyadri, Kuvempu University, Shankargatta, 577451, Karnataka, India.
authors.forename: H N
authors.initials: HN
authors.lastname: Naveen Kumar
authors.affiliation: Department of Chemistry, Centre of Bio-Medical Research (CBMR), Sanjay Gandhi Post Graduate Institute of Medical Sciences Campus, Raebareli Road, Lucknow, 226014, Uttar Pradesh, India.
authors.forename: K
authors.initials: K
authors.lastname: Misra
authors.affiliation: Department of Neurochemistry, National Institute of Mental Health and Neurosciences, No. 2900, Hosur Road, Bangalore, 560029, Karnataka, India. bharath@nimhans.ac.in.|Neurotoxicology Laboratory at the Neurobiology Research Center, National Institute of Mental Health and Neurosciences, No. 2900, Hosur Road, Bangalore, 560029, Karnataka, India. bharath@nimhans.ac.in.
authors.forename: M M
authors.initials: MM
authors.lastname: Srinivas Bharath
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology*; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D004331:Drosophila melanogaster; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D012402:Rotenone / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D012402:Rotenone; D003474:Curcumin
keywords: Antioxidant; Bioavailability; Curcumin; Drosophila melanogaster; Neuroprotection; Parkinson’s disease; Rotenone