title: Oxymatrine inhibits microglia activation via HSP60-TLR4 signaling.
abstract: Oxymatrine (OMT) is an alkaloid extracted fromSophora flavescens, which has broad anti-inflammatory, antitumor and immunosuppressant actions. However, the underlying molecular mechanisms have remained elusive. Heat shock protein 60 (HSP60) has recently been shown to have an important role in autoimmune reactions. The present study aimed to investigate whether OMT exerts its anti-inflammatory effects by inhibiting microglial activation and examined the role of HSP60 in this process. Western blot analysis and ELISA showed that OMT decreased the expression and release of HSP60 by LPS-activated BV2 cells. The expression of heat shock factor 1, the transcription factor of HSP60, was also suppressed by OMT. Extracellular HSP60 has been previously indicated to induce microglial apoptosis through the Toll-like receptor (TLR)-4 pathway. Flow cytometric analysis demonstrated that LPS treatment induced apoptosis of BV2 cells, which was inhibited by OMT in parallel with inhibition of LPS-induced expression of TLR-4. Furthermore, OMT was shown to suppress the levels of myeloid differentiation factor (MYD)88, nuclear factor (NF)-κB, caspase-3, inducible nitric oxide synthase, tumor necrosis factor-α, interleukin (IL)-1β and IL-6. In light of these results, it was concluded that OMT may exert its neuroprotective effects via HSP60/TLR-4/MYD88/NF-κB signaling pathways to inhibit microglial activation. OMT may therefore offer substantial therapeutic potential for treating neurodegenerative diseases associated with microglial activation.
authors.affiliation: Department of Neurobiology, Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Feijia
authors.initials: F
authors.lastname: Ding
authors.affiliation: Department of Neurobiology, Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Yunhong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Hou
authors.affiliation: Department of Neurobiology, Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Shuting
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Neurobiology, Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
keywords: BV2 microglia; Toll-like receptor 4; heat shock protein 60; oxymatrine