Effects Of Vanillin On Inflammatory-mediated Parkinson's Disease Models

Parkinson's disease(PD)is a common neurodegenerative disease which occur with elder.And in recent years there is a tendency with younger.The etiology of PD is not clear,a large number of studies have shown that microglia-mediated neuroinflammatory plays a vital role in its process.Similar to the function of macrophage in the peripheral system,microglia is a kind of glial cells,which is the main effector of the neuroinflammatory.Over activated microglia can produce TNF-?,IL-1? and IL-6 and other inflammatory mediators,which will damage dopaminergic neurons.The damage signal will active the microglia again,and thus the malignant circulation begins.So inhibiting microglia-mediated neuroinflammation may be a potential treatment for PD.Vanillin is an aromatic aldehyde compound,which is one of the main ingredients of natural herbs.It is widely used as spices and food additives.Vanillin has a significant anti-inflammatory effect in peripheral tissues and cells such as the liver,colon and macrophages.In addition,vanillin play a mitigation effect in PD induced by the rotenone,but the mechanism is not clear.Therefore,we hypothesize that vanillin may play a therapeutic role in PD by inhibiting microglia-mediated neurotoxicity.Based on this,we establish the neuroinflammatory mediated PD rat model through the substantia nigra injection of LPS by the brain stereotaxic technique in the first part of the work.At the same time intraperitoneal injection with different concentrations of vanillin is done,then we detect the rotation behavior,effect of dopaminergic neuronal injury and activation of microglia in substantia nigra of the rat model.The results showed that the apomorphine could induce the rotation behavior of PD rats after the injection of LPS in the substantia nigra.Different doses of vanillin(5 mg / kg / day,10 mg / kg / day and 20 mg / kg / day)were given to the rats by intraperitoneal injection on the second week and the fourth week of modeling.The results showed that vanillin could relieve the apomorphine-induced rotation behavior in the does-dependent way.In the substantia nigra area,the dopaminergic neurons injury and microglia activation were serious after the injection of LPS.Vanillin can protect the dopaminergic neurons and inhibit microglia activation.These results suggest that vanillin inhibits the activation of microglia in the inflammatory-mediated PD,which plays a neuroprotective effect on dopaminergic neurons.Based on the first part,we began the second part with the vitro microglia inflammatory response model induced by LPS.We added vanillin to explore its effects and mechanism.We found that vanillin inhibited the expression of m RNA and proteins of some inflammatory factors and proinflammatory enzymes.Vanillin inhibited the phosphorylation of MAPK p38,ERK1 / 2 and NF-?B p65 induced by LPS,however,there is no significant effect on phosphorylation of JNK.The above results indicate that vanillin has a therapeutic or alleviating effect on the PD rat model by inhibiting microglia-mediated neuroinflammation.Therefore,vanillin may be a potential drug for the treatment of PD.