A novel target TAX1BP1 and P38/Nrf2 pathway independently involved in the anti-neuroinflammatory effect of isobavachalcone.

A novel target TAX1BP1 and P38/Nrf2 pathway independently involved in the anti-neuroinflammatory effect of isobavachalcone.
Free Radic Biol Med. 2020 Apr 17;:
Authors: Li Z, Wang Q, Luan H, Yang M, Li Y, Tian G, Hen W
Abstract
Isobavachalcone (IBC) is a natural compound isolated from Fructus psoraleae. In recent years, IBC has been reported to exert anti-neuroinflammatory effect, but precise mechanisms of action remain unclear. The current study is focused on elucidating the underlying molecular mechanisms. Toward this goal, we conducted experiments to examine the inhibitory effect of IBC on microglia activation in vitro and in vivo, the results showed that IBC can inhibit microglia activation compared to the LPS only treatment group. Further studies on the mechanisms showed IBC can increase TAX1BP1 expression which further induced an increased interaction with ubiquitin-editing enzyme A20. We found the novel target TAX1BP1 was involved in the inhibitory effect of IBC on microglia activation via TRAF6 degradation and inhibition of NF-κB pathway. Meanwhile, we found that IBC can obviously induce activation of Nrf2/HO-1 via P38 pathway activation. All these results demonstrated IBC can inhibit microglia activation through upregulation of TAX1BP1 and activation of P38/Nrf2 pathway. Importantly, we found TAX1BP1 as a novel target for inhibitory effect of IBC on microglia activation independently from P38/Nrf2 pathway. This present study...

Source: Free Radical Biology and Medicine - April 16, 2020 Category: Biology Authors: Li Z, Wang Q, Luan H, Yang M, Li Y, Tian G, Hen W Tags: Free Radic Biol Med Source Type: research