Anti-Inflammatory Role of the Isoflavone Diadzein in Lipopolysaccharide-Stimulated Microglia: Implications for Parkinson’s Disease

Abstract

Microglial activation and subsequent release of toxic pro-inflammatory factors are believed to play an important role in neuronal cell death associated with Parkinson’s disease (PD). Compounds that inhibit microglia activation and suppress pro-inflammatory factor release have been reported to have neuroprotective effects in animal models of PD. In this study, we tested whether diadzein, a natural isoflavone found in soybean, attenuated lipopolysaccharide (LPS)-induced release of inflammatory mediators in BV-2, a murine microglial cell line. Diadzein pretreatment was found to significantly suppress the production of the pro-inflammatory factors nitric oxide and IL-6 as well as their mRNA expression in conjunction with reductions in ROS production, p38 MAPK phosphorylation, and NF-κB activation. Furthermore, transfer of conditioned media (CM) from BV-2 cells pretreated with diadzein resulted in a significantly reduction in dopaminergic neurotoxicity compared with CM from microglia stimulated with LPS alone. Together, our results suggest that diadzein’s neuroprotective properties may be due to its ability to dampen induction of microglial activation and the subsequent release of soluble pro-inflammatory factors. This appears to be via inhibition of oxidative induction of the p38 MAP kinase-NFκB pathway, resulting in reduced expression of pro-inflammatory genes and release of their corresponding gene products.

Daidzein suppresses pro-inflammatory chemokine Cxcl2 transcription in TNF-α-stimulated murine lung epithelial cells via depressing PARP-1 activity

“…Daidzein pretreatment was found to significantly suppress LPS-induced mRNA expression of the pro-inflammatory factors nitric oxide and IL-6 in murine microglial cells, which suggests the neuroprotective properties of daidzein [28] . Release of soluble pro-inflammatory factors appears to be via inhibition of oxidative induction and activation of the p38 MAP kinase-NF-κB pathway [28] .…”

“…Release of soluble pro-inflammatory factors appears to be via inhibition of oxidative induction and activation of the p38 MAP kinase-NF-κB pathway [28] . Another study showed that daidzein significantly inhibited the production of NO and IL-6 and decreased the mRNA expression of NOS and IL-6 in LPS-treated RAW264.7 cells; however, the JNK and p38 pathways were not involved in daidzein-mediated suppression of NF-κB-mediated transcription [6] .…”

RNF11 modulates microglia activation through NF-κB signalling cascade

“…Previous reports have used BV2 cells to demonstrate the role of microglia in neuroinflammation [4, 6, 7, 34]. In our study we used the BV2 cells to alter RNF11 levels since primary microglial cultures resist transfection or transduction protocols.…”

Adaptive Cellular Stress Pathways as Therapeutic Targets of Dietary Phytochemicals: Focus on the Nervous System

“…Thus, low amounts of phytoestrogens can protect against various cancers such as prostate, breast, bowel, and other cancers (Adlercreutz, 2002;Zhao and Mu, 2011). Moreover, soy isoflavones, including genistein and daidzein, can protect neurons in animal models of ALS, stroke, chronic sciatic nerve injury, and PD (Trieu and Uckun, 1999;Liu et al, 2008;Valsecchi et al, 2008;Chinta et al, 2013). Interestingly, findings suggest that soy isoflavones can improve cognitive function in postmenopausal women (Kritz-Silverstein et al, 2003).…”