Open AccessKurarinone alleviates hemin‐induced neuroinflammation and microglia‐mediated neurotoxicity by shifting microglial M1 / M2 polarization via regulating the IGF1 / PI3K /Akt signaling
Author(s) -
Jia ZengQiang,
Zuo Cheng,
Yue WenFeng
Publication year - 2022
Publication title -
the kaohsiung journal of medical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.439
H-Index - 36
eISSN - 2410-8650
pISSN - 1607-551X
DOI - 10.1002/kjm2.12597
Subject(s) - neuroinflammation , microglia , protein kinase b , pi3k/akt/mtor pathway , neurotoxicity , medicine , hemin , neuroprotection , signal transduction , pharmacology , microbiology and biotechnology , cancer research , inflammation , immunology , biochemistry , biology , heme , toxicity , enzyme
Cerebral hemorrhage is a fatal disease that causes severe damage to local nerve function. The purpose of this research is to analyze the effect of kurarinone on hemin‐induced neuroinflammation and neurotoxicity. In our study, according to the results of bioinformatics analysis, we hypothesized that kurarinone might modulate cerebral hemorrhage advancement via the insulin‐like growth factor 1/phosphoinositide 3‐kinase/protein kinase B (IGF1/PI3K/Akt) signaling. Kurarinone promoted M2 microglia polarization, and curbed M1 polarization and inflammation in human microglial cells (HMC3) cells with hemin treatment. Besides, kurarinone upregulated IGF1 expression and activated the PI3K/Akt signaling pathway in hemin‐treated HMC3 cells. In addition, downregulation of IGF1 or inhibition of the PI3K/Akt signaling weakened the effects of kurarinone on microglia polarization and inflammation in HMC3 cells with hemin treatment. Kurarinone alleviated apoptosis and oxidative damage of SH‐SY5Y cells co‐cultured with hemin‐treated HMC3 cells. In conclusion, kurarinone lessened hemin‐induced neuroinflammation and microglia‐mediated neurotoxicity by regulating microglial polarization through modulating the IGF1/PI3K/Akt signaling. These results delivered a new prospective therapeutic drug for the treatment of cerebral hemorrhage.