Icariin attenuates lipopolysaccharide-induced microglial activation and resultant death of neurons by inhibiting TAK1/IKK/NF-κB and JNK/p38 MAPK pathways

• Published in: International immunopharmacology 2010-06, Vol.10 (6), p.668-678
• Main Authors: Zeng, Ke-Wu, Fu, Hong, Liu, Geng-Xin, Wang, Xue-Mei
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Icariin; Medical sciences; Microglia; Mitogen-activated protein kinase (MAPK); Neuroinflammatory; Nuclear factor-κB (NF-κB); Pharmacology. Drug treatments
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2010.03.010

Microglia in the central nervous system (CNS) play an important role in the initiation of neuroinflammatory response. Icariin, a compound from Epimedium brevicornum Maxim, has been reported to have anti-inflammatory effect on the macrophage cell line RAW264.7. However, it is currently unknown what anti-inflammatory role icariin may play in the CNS. Here, we reported the discovery that icariin significantly inhibited the release of nitric oxide (NO), prostaglandin E (PGE)-2, reactive oxygen species (ROS) and mRNA expression of proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in lipopolysaccharide (LPS)-activated microglia. Icariin also inhibited the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 in a dose-dependent manner. Further mechanism studies revealed that icariin blocked TAK1/IKK/NF-κB and JNK/p38 MAPK pathways. It was also found that icariin reduced the degeneration of cortical neurons induced by LPS-activated microglia in neuron–microglia co-culture system. Taken together these findings provide mechanistic insights into the suppressive effect of icariin on LPS-induced neuroinflammatory response in microglia, and emphasize the neuroprotective effect and therapeutic potential of icariin in neuroinflammatory diseases.