Curcumin Protects Dopaminergic Neuron Against LPS Induced Neurotoxicity in Primary Rat Neuron/Glia Culture

Abstract

Using primary rat mesencephalic neuron-glia cultures as an in vitro model of Parkinson's disease (PD), we tested the effect of curcumin, a natural dietary pigment with well-known anti-inflammation effects, on dopaminergic (DA) degeneration. Curcumin pretreatment mitigated LPS-induced DA neurotoxicity in a concentration-dependent manner and curcumin post-treatment also showed protective effect. Microglia depletion abolished this protective effect of curcumin, indicating that microglia play an important role in this effect. Supportively, observation by immunocytochemistry staining using OX-42 antibody showed that curcumin treatment inhibited LPS-induced morphological change of microglia. Besides, LPS-induced production of many proinflammatory factors and their gene expressions decreased dramatically after curcumin treatment. Results also revealed that curcumin treatment decreased LPS-induced activation of two transcription factors--nuclear factors kappaB (NF-kappaB) and activator protein-1 (AP-1). Taken together, our study implicated that curcumin might be a potential preventive and therapeutic strategy for inflammation-related neurodegenerative diseases.

Anti-inflammatory Activity of Salvianolic Acid B in Microglia Contributes to its Neuroprotective Effect

“…Careful targeting of these cells could have therapeutic benefits for several types of trauma and disease specific to the central nervous system. Previous in vivo or in vitro studies have revealed that drugs such as tetracyclines [30], histone deacetylase inhibitors [31], naloxone [32], dextromethorphan [33], curcumin [28] and several polyphenolic plant-derived flavonoids [27] afford neuroprotection through modulating microglial cells. Of course, we should not seriously hamper their critical role in host defense and their neuroregenerative properties when modulating the deleterious aspects of activated microglia.…”

“…It's also an important target of several anti-inflammatory drugs [27,28]. Recent experiment evidence demonstrates that Sal B can suppress NF-jB activation in endothelial cell [16,18] and mesangial cell [19].…”

<b>ADAM17 regulates TNF-α expression upon lipopolysaccharide stimulation in oral </b><b>keratinocytes </b>

“…LPS stimulation enhanced the level of ADAM17 and TNF-α secreted from oral keratinocytes, although differences in the level of enhancement existed with respect to the origin, concentration and time of LPS exposure to the cells. Previous studies report that the signaling pathway of P. gingivalis LPS differs from that of E. coli LPS in cells (22), which leads to differential immune responses with respect to mRNA expression levels and the time course of each cytokine (5). Thus, differences in TNF-α levels released from cells following E.…”

Inflammatory Responses and Regulation in Parkinson’s Disease

“…In an experimental allergic encephalomyelitis (EAE) mouse model of MS, curcumin inhibited EAE development by attenuating microglia activation and IL-12 production as well as Th1 cell differentiation (Natarajan and Bright 2002). Curcumin also has shown protective effects against LPS-induced DA neuron cell death in mixed rat neuron-glial cell cultures which were mediated by inhibition of the production of proinflammatory factors in microglia (Yang, Zhang et al 2008). Taken together, the neuroprotective results from these three natural plant products suggest an interesting possibility for PD therapeutics.…”