Bioconjugates of curcumin display improved protection against glutathione depletion mediated oxidative stress in a dopaminergic neuronal cell line: Implications for Parkinson’s disease

• Published in: Bioorganic & medicinal chemistry Vol. 18; no. 7; pp. 2631 - 2638
• Main Authors: Harish, G., Venkateshappa, C., Mythri, Rajeswara Babu, Dubey, Shiv Kumar, Mishra, Krishna, Singh, Neetu, Vali, Shireen, Bharath, M.M. Srinivas
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.04.2010; Elsevier
• Subjects: Anticonvulsants. Antiepileptics. Antiparkinson agents; Antioxidants - chemical synthesis; Antioxidants - pharmacology; Bioconjugates; Biological and medical sciences; Biological Availability; Cell Line; Curcumin; Curcumin - analogs & derivatives; Curcumin - chemistry; Curcumin - pharmacology; Dopamine - physiology; Dopaminergic cell line; Glutathione; Glutathione - metabolism; Glutathione Transferase - metabolism; Humans; Hydrogen Peroxide - metabolism; Indicators and Reagents; Lipid Peroxidation - drug effects; Medical sciences; Models, Molecular; Neurodegeneration; Neurons - drug effects; Neurons - metabolism; Neuropharmacology; Neuroprotective Agents - chemical synthesis; Neuroprotective Agents - pharmacology; Oxidants - metabolism; Oxidative stress; Oxidative Stress - drug effects; Parkinson Disease - drug therapy; Pharmacology. Drug treatments; Reactive Oxygen Species - metabolism; γ-GCL; GSSG; Oxidative stress; DTNB; H2O2; D1; D2; D3; glu; Dopaminergic cell line; PD; Bioconjugates; Neurodegeneration; ROS; Curcumin; SN; MPTP; cys; GSH; BSO; Glutathione; Nervous system diseases; Tripeptide; Parkinson disease; Antioxidant; In vitro; Biological activity; Cell line; Neuron; Sulfur peptide; Degenerative disease; Conjugated compound; Chemical synthesis; Valine derivatives
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2010.02.029

Oxidative stress is implicated in mitochondrial dysfunction associated with neurodegeneration in Parkinson’s disease (PD). Depletion of the cellular antioxidant glutathione (GSH) resulting in oxidative stress is considered as an early event in neurodegeneration. We previously showed that curcumin, a dietary polyphenol from turmeric induced GSH synthesis in experimental models and protected against oxidative stress. Here we tested the effect of three bioconjugates of curcumin (involving diesters of demethylenated piperic acid, valine and glutamic acid) against GSH depletion mediated oxidative stress in dopaminergic neuronal cells and found that the glutamic acid derivative displayed improved neuroprotection compared to curcumin.