Curcumin exerts anti-inflammatory and antioxidative properties in 1-methyl-4-phenylpyridinium ion (MPP+)-stimulated mesencephalic astrocytes by interference with TLR4 and downstream signaling pathway

Abstract

Neuroinflammation is closely associated with the pathophysiology of neurodegenerative diseases including Parkinson's disease (PD). Recent evidence indicates that astrocytes also play pro-inflammatory roles in the central nervous system (CNS) by activation with toll-like receptor (TLR) ligands. Therefore, targeting anti-inflammation may provide a promising therapeutic strategy for PD. Curcumin, a polyphenolic compound isolated from Curcuma longa root, has been commonly used for the treatment of neurodegenerative diseases. However, the details of how curcumin exerts neuroprotection remain uncertain. Here, we investigated the protective effect of curcumin on 1-methyl-4-phenylpyridinium ion-(MPP(+)-) stimulated primary astrocytes. Our results showed that MPP(+) stimulation resulted in significant production of tumor necrosis factor (TNF)-α, interleukin (IL-6), and reactive oxygen species (ROS) in primary mesencephalic astrocytes. Curcumin pretreatment decreased the levels of these pro-inflammatory cytokines while increased IL-10 expression in MPP(+)-stimulated astrocytes. In addition, curcumin increased the levels of antioxidant glutathione (GSH) and reduced ROS production. Our results further showed that curcumin decreased the levels of TLR4 and its downstream effectors including NF-κB, IRF3, MyD88, and TIRF that are induced by MPP(+) as well as inhibited the immunoreactivity of TLR4 and morphological activation in MPP(+)-stimulated astrocytes. Together, data suggest that curcumin might exert a beneficial effect on neuroinflammation in the pathophysiology of PD.

The Emerging Role of Curcumin in the Modulation of TLR-4 Signaling Pathway: Focus on Neuroprotective and Anti-Rheumatic Properties

“…Recent reports suggest that due to curcumin's ability to reduce Beta-amyloid plaques, delay degradation of neurons, as well as decrease inflammatory microglia responses, the overall memory in patients with AD results significantly improved [153,154].…”

Protective Effects of Curcumin on Manganese-Induced BV-2 Microglial Cell Death

“…24) Recent studies have also revealed that curcumin has protective effects against PD-related neurotoxicants, such as MPP + , rotenone, salsolinol, and 6-hydroxydopamine (6-OHDA) in neurons and/or glial cells. 14,15,25) However, the effects of curcumin against Mn toxicity in microglia have not been reported. Therefore, this study investigated that curcumin can suppress Mn-induced cytotoxicity in BV-2 microglial cells.…”

“…12,13) Further, curcumin effectively protected neurons and/or glial cells against various neurotoxins. 14,15) However, the effect of curcumin against Mn-induced cell death has not been studied. In the present study, we examined the possible protective effect of curcumin against Mn-induced BV-2 microglial cell damage.…”

Curcumin Protects an SH-SY5Y Cell Model of Parkinson’s Disease Against Toxic Injury by Regulating HSP90

“…A study of van de Merwe et al proposed that curcumin (Cur) protected against PD injury in a PINK1-knockdown cell model [2]. Cur, or diferuloylmethane, is a natural ingredient extracted from Curcuma longa rhizome [5,6]. It has attracted great interest for its numerous pharmacological properties such as anti-inflammation, antioxidant, anti-tumor and anti-nerve degeneration [2,7].…”

“…For instance, Liu et al demonstrated that Cur was protective in PC12 cell models of PD stimulated by A53T α-synuclein [9]. Yu et al investigated via an MPP + -introduced PD model suggested that the anti-inflammatory and anti-oxidative roles of Cur were by interacting with TLR4 and its downstream effectors [5]. Cui et al emphasized its mitigation on PD dopaminergic neural damage, of which increased tyrosine hydroxylase (TH) activity was included as a parameter [8].…”