Vanillin Protects Dopaminergic Neurons against Inflammation-Mediated Cell Death by Inhibiting ERK1/2, P38 and the NF-κB Signaling Pathway

• Published in: International journal of molecular sciences 2017-02, Vol.18 (2), p.389-389
• Main Authors: Yan, Xuan, Liu, Dian-Feng, Zhang, Xiang-Yang, Liu, Dong, Xu, Shi-Yao, Chen, Guang-Xin, Huang, Bing-Xu, Ren, Wen-Zhi, Wang, Wei, Fu, Shou-Peng, Liu, Ju-Xiong
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Benzaldehydes - pharmacology; Cell Death; Cell Line; Cyclooxygenase-2; Cytokines - metabolism; Dopamine receptors; Dopaminergic Neurons - drug effects; Dopaminergic Neurons - metabolism; Dopaminergic Neurons - pathology; Extracellular signal-regulated kinase; Inflammation; Inflammation - metabolism; Inflammation - pathology; Inflammation Mediators - metabolism; Injection; Interleukin 6; Lipopolysaccharides; Lipopolysaccharides - metabolism; Male; MAP Kinase Signaling System - drug effects; MAPK; Microglia; Microglia - drug effects; Microglia - metabolism; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Motor Activity - drug effects; Motor task performance; Neurodegeneration; Neurons; Neuroprotective Agents - pharmacology; NF-kappa B - metabolism; NF-κB; Nitric oxide; Nitric-oxide synthase; p38 Mitogen-Activated Protein Kinases; Parkinson’s disease; Rats; Rodents; Signal transduction; Signal Transduction - drug effects; Substantia nigra; Vanillin
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms18020389

Neuroinflammation plays a very important role in the pathogenesis of Parkinson's disease (PD). After activation, microglia produce pro-inflammatory mediators that damage surrounding neurons. Consequently, the inhibition of microglial activation might represent a new therapeutic approach of PD. Vanillin has been shown to protect dopaminergic neurons, but the mechanism is still unclear. Herein, we further study the underlying mechanisms in lipopolysaccharide (LPS)-induced PD models. In vivo, we firstly established rat models of PD by unilateral injection of LPS into substantia nigra (SN), and then examined the role of vanillin in motor dysfunction, microglial activation and degeneration of dopaminergic neurons. In vitro, murine microglial BV-2 cells were treated with vanillin prior to the incubation of LPS, and then the inflammatory responses and the related signaling pathways were analyzed. The in vivo results showed that vanillin markedly improved the motor dysfunction, suppressed degeneration of dopaminergic neurons and inhibited microglial over-activation induced by LPS intranigral injection. The in vitro studies demonstrated that vanillin reduces LPS-induced expression of inducible nitric oxide (iNOS), cyclooxygenase-2 (COX-2), IL-1β, and IL-6 through regulating ERK1/2, p38 and NF-κB signaling. Collectively, these data indicated that vanillin has a role in protecting dopaminergic neurons via inhibiting inflammatory activation.