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.

Evaluation of the Neuroprotective Effects of Curcuminoids on B35 and SH-SY5Y Neuroblastoma Cells

“…With the higher concentrations of H 2 O 2 (500 and 1,000 µM), 20 µM of curcumin showed the best neuroprotection; whereas with the lower concentrations of H 2 O 2 (100 and 300 µM), 5 µM of curcumin was sufficient to improve cell viability. Protecting SH-SY5Y cells from oxidative stress and beta amyloid induced neurotoxicity by treating them with curcumin have also been shown in other studies [6,7,17,[27][28][29]. Further research is needed to explain the mechanism behind the differences in cell viability when curcumin is used as pretreatment versus post-treatment in SH-SY5Y cells.…”

An Overview of Crucial Dietary Substances and Their Modes of Action for Prevention of Neurodegenerative Diseases

“…Additionally, nephrocizin is capable of diffusing through the cell membranes and scavenges the hydroxyl radical directly. Similarly, Meesarapee et al [125] showed that pretreatment of human neuroblastoma SH-SY5Y cells exposed to 6-OHDA by curcumin effectively reduces cell death by decreasing the levels of quinone-bound proteins.…”

“…Polyphenols also modulate the mitogen-activated protein kinase (MAPK) pathways that is involved in cell survival and apoptosis, and might have roles in the protection against oxidative stress. For example, curcumin [125] and naringenin [112] reduced the phosphorylation of MAPKs and the levels of cleaved caspase-3 in human neuroblastoma SH-SY5Y cells exposed to 6-OHDA. Curcumin and naringenin also prevented intracellular Ca 2+ increases, ROS production, and decreased apoptosis through mitigation of the expression and activity of pro-apoptotic factors [126].…”

Inflammation: Role in Parkinson's Disease and Target for Therapy

“…In addition, flavonoids from Selaginella species have the ability to increase the expression and activity of anti-oxidative enzymes endogenously [104], and the aqueous extract of Selaginella suppresses rotenone induced neurotoxicity, attenuated locomotor dysfunction, oxidative stress, and mitochondrial dysfunction in Drosophila melanogaster [105]. Polyphenols may also target MAPK pathways and apoptosis, since phosphorylation of MAPK and expression of cleaved caspase 3 were reduced in 6-OHDA induced SHSY-5Y cells by curcumin [106]. Similarly, the phosphorylation of NF-kB, JNK, and ERK was inhibited by flavone baicalein in MPP + -induced primary astrocytes and indicated its implication in the treatment of PD [107].…”