NRF2/HO-1 activation via ERK pathway involved in the anti-neuroinflammatory effect of Astragaloside IV in LPS induced microglial cells

Abstract

The anti-neuroinflammatory effect of Astragaloside IV (ASI) has been reported, but its underlying mechanisms are unclear. This study is further to explore the underlying mechanism of ASI on anti-neuroinflammatory effect in LPS induced microglia cells. The result showed ASI significantly reduced the production of inflammatory mediators NO, TNF-α and IL-6 in BV2 and primary microglial cells. Western blot analysis showed ASI did not inhibit the MAPK activation, on the contrary, the results showed ASI can obviously induce the ERK activation. We also examined the NRF2 and HO-1 activation which were reported to exert anti-neuroinflammatory effect and the results presented it could induce the activation of HO-1 downstream NRF2 in BV2 microglial cells. Further study indicated the NRF2/HO-1 activation via ERK pathway activation. After NRF2 siRNA or HO-1 inhibitor treatment, the anti-neuroinflammatory effect of ASI was attenuated obviously compared with the normal group. Taken together, this study demonstrated that the activation of NRF2/HO-1 via ERK signaling pathway is a novel mechanism of ASI which exerted anti-neuroinflammatory activity in microglia cells, it could be an attractive candidate for the regulation of inflammatory responses in the brain.

Keywords: Astragaloside IV; HO-1; Inflammatory; Microglial; NRF2.