A novel AMPK activator hernandezine inhibits LPS-induced TNF alpha production

作者：Li, Ping; Li, Xiaofang; Wu, Yonghong; Li, Manxiang^*; Wang, Xiaochuang^*

来源：Oncotarget, 2017, 8(40): 67218-67226.

DOI：10.18632/oncotarget.18365

• hernandezine
• LPS
• AMPK
• TNF alpha
• NF kappa B

Here, we found that hernandezine, a novel AMPK activator, inhibited LPS-induced TNF alpha expression/production in human macrophage cells (THP-1 and U937 lines). Activation of AMPK is required for hernandezine-induced anti-LPS response. AMPK alpha shRNA or dominant negative mutation (T172A) blocked hernandezine-induced AMPK activation, which almost completely reversed anti-LPS activity by hernandezine. Exogenous expression of the constitutively activate AMPK alpha (T172D, caAMPK alpha) also suppressed TNF alpha production by LPS. Remarkably, hernandezine was unable to further inhibit LPS-mediated TNF alpha production in caAMPK alpha-expressing cells. Hernandezine inhibited LPS-induced reactive oxygen species (ROS) production and nuclear factor kappa B (NF kappa B) activation. Treatment of hernandezine in ex-vivo cultured primary human peripheral blood mononuclear cells (PBMCs) also largely attenuated LPS-induced TNF alpha production. Together, we conclude that AMPK activation by hernandezine inhibits LPS-induced TNF alpha production in macrophages/monocytes.

• 出版日期2017-9-15
• 单位西安交通大学; 西安医学院