title: Curcumin I mediates neuroprotective effect through attenuation of quinoprotein formation, p-p38 MAPK expression, and caspase-3 activation in 6-hydroxydopamine treated SH-SY5Y cells.
abstract: 6-Hydroxydopamine (6-OHDA) selectively enters dopaminergic neurons and undergoes auto-oxidation resulting in the generation of reactive oxygen species and dopamine quinones, subsequently leading to apoptosis. This mechanism mimics the pathogenesis of Parkinson's disease and has been used to induce experimental Parkinsonism in both in vitro and in vivo systems. In this study, we investigated the effects of curcumin I (diferuloylmethane) purified from Curcuma longa on quinoprotein production, phosphorylation of p38 MAPK (p-p38), and caspase-3 activation in 6-OHDA-treated SH-SY5Y dopaminergic cells. Pretreatment of SH-SY5Y with curcumin I at concentrations of 1, 5, 10, and 20 μM, significantly decreased the formation of quinoprotein and reduced the levels of p-p38 and cleaved caspase-3 in a dose-dependent manner. Moreover, the levels of the dopaminergic neuron marker, phospho-tyrosine hydroxylase (p-TH), were also dose-dependently increased upon treatment with curcumin I. Our results clearly demonstrated that curcumin I protects neurons against oxidative damage, as shown by attenuation of p-p38 expression, caspase-3-activation, and toxic quinoprotein formation, together with the restoration of p-TH levels. This study provides evidence for the therapeutic potential of curcumin I in the chemoprevention of oxidative stress-related neurodegeneration.
authors.affiliation: Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Benjawan
authors.initials: B
authors.lastname: Meesarapee
authors.forename: Anusorn
authors.initials: A
authors.lastname: Thampithak
authors.forename: Yamaratee
authors.initials: Y
authors.lastname: Jaisin
authors.forename: Pimtip
authors.initials: P
authors.lastname: Sanvarinda
authors.forename: Apichart
authors.initials: A
authors.lastname: Suksamrarn
authors.forename: Patoomratana
authors.initials: P
authors.lastname: Tuchinda
authors.forename: Noppawan Phumala
authors.initials: NP
authors.lastname: Morales
authors.forename: Yupin
authors.initials: Y
authors.lastname: Sanvarinda
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D030024:Curcuma / Q000737:chemistry; D003474:Curcumin / Q000494:pharmacology*; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D016627:Oxidopamine / Q000494:pharmacology*; D010766:Phosphorylation; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D018696:Neuroprotective Agents; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D048051:p38 Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D003474:Curcumin
keywords: 6-OHDA; cleaved caspase-3; curcumin I; p-TH; p38 MAPK; quinoprotein