Neuroprotective Effects of B-Type Cinnamon Procyanidin Oligomers on MPP+-Induced Apoptosis in a Cell Culture Model of Parkinson's Disease

Abstract

Cinnamon procyanidin oligomers (CPOs) are water-soluble components extracted from cinnamon. This study aims to explore the neuroprotection of B-type CPO (CPO-B) against 1-methyl-4-phenylpyridinium (MPP⁺)-mediated cytotoxicity and the molecular mechanisms underlying its protection. The results demonstrated that CPO-B showed protection by increasing cell viability, attenuating an intracellular level of reactive oxygen species, downregulating cleaved caspase-3 expression, and upregulating the Bcl-2/Bax ratio. Moreover, CPO-B completely blocked the dephosphorylation of extracellular, signal-regulated kinase 1 and 2 (Erk1/2) caused by MPP⁺. Treatment with an Erk1/2 inhibitor, SCH772984, significantly abolished the neuroprotection of CPO-B against MPP⁺. Taken together, we demonstrate that CPO-B from cinnamon bark provided protection against MPP⁺ in cultured SH-SY5Y cells, and the potential mechanisms may be attributed to its ability to modulate the dysregulation between pro-apoptotic and anti-apoptotic proteins through the Erk1/2 signaling pathway. Our findings suggest that the addition of cinnamon to food or supplements might benefit patients with PD.

Keywords: CPO-B; Erk1/2; MPP+; Parkinson’s disease; neuroprotection.

Figure 1

The effect of CPO-B on MPP⁺-induced cytotoxicity measured by intracellular ROS generation (a, n = 4), cell viability (b, n = 8), microscopic examination (c) and Hoechst nuclear staining (d); the values (mean ± SEM) were standardized to the percentage of control; symbol * indicates the difference between control and other treatments; symbol # indicates the difference between MPP⁺ and MPP⁺+CPO-B; ** p < 0.01, *** p < 0.001, # p < 0.05, ## p < 0.01; CPO-B, B-type cinnamon procyanidin oligomer; MPP⁺, 1-methyl-4-phenylpyridinium.

Figure 2

The effect of CPO-B on MPP⁺-induced alteration of Bcl-2/Bax expression (b, n = 3) and cleaved caspase-3 expression (c, n = 3). The top panel shows the representative Western blots (a); the values (mean ± SEM) were standardized to the percentage of control; symbol * indicates the difference between control and other treatments; symbol # indicates the difference between MPP⁺ and MPP⁺+CPO-B; * p < 0.05, ** p < 0.01, # p < 0.05, ### p < 0.001; CPO-B, B-type cinnamon procyanidin oligomer; MPP⁺, 1-methyl-4-phenylpyridinium; Bcl-2, B-cell lymphoma 2; Bax, Bcl-2-associated X protein; GAPDH, glyceraldehyde 3-phosphate dehydrogenase.

Figure 3

The effect of CPO-B on the MPP⁺-induced alteration of Erk1/2 (b, n = 3) and Akt phosphorylation (c, n = 3). The top panel in the figure shows representative Western blots (a). The values (mean ± SEM) were normalized to control; symbol * indicates the difference between control and other treatments; symbol # indicates the difference between MPP⁺ and MPP⁺+CPO-B; ** p < 0.01, *** p < 0.001, # p < 0.05; CPO-B, B-type cinnamon procyanidin oligomer; MPP⁺, 1-methyl-4-phenylpyridinium; AKT, protein kinase B; P-AKT, phosphorylated AKT; T-AKT, total AKT; Erk1/2, extracellular signal regulated kinase 1 and 2; P-Erk1/2, phosphorylated Erk1/2; T-Erk1/2, total Erk1/2; GAPDH, glyceraldehyde 3-phosphate dehydrogenase.

Figure 4

The effect of Erk1/2 inhibition on CPO-B-mediated neuroprotection measured by cell viability (a, n = 3), Erk1/2 phosphorylation (c, n = 3) and Bcl-2/Bax expression ratio (d, n = 3). The top panel in the figure shows representative Western blots (b). The values (mean ± SEM) were normalized to control; symbol * indicates the difference between control and other treatments; symbol # indicates the difference between MPP⁺ and MPP⁺+CPO-B; * p < 0.05, ** p < 0.01, *** p < 0.001, # p < 0.05, ## p < 0.01. CPO-B, B-type cinnamon procyanidin oligomer; MPP⁺, 1-methyl-4-phenylpyridinium; Bcl-2, B-cell lymphoma 2; Bax, Bcl-2-associated X protein; Erk1/2, extracellular signal-regulated kinase 1 and 2; P-Erk1/2, phosphorylated Erk1/2; T-Erk1/2, total Erk1/2; GAPDH, glyceraldehyde 3-phosphate dehydrogenase.