Pseudoginsenoside-F11 (PF11) exerts anti-neuroinflammatory effects on LPS-activated microglial cells by inhibiting TLR4-mediated TAK1/IKK/NF-κB, MAPKs and Akt signaling pathways.
Pseudoginsenoside-F11 (PF11), an ocotillol-type ginsenoside, has been shown to possess significant neuroprotective activity. Since microglia-mediated inflammation is critical for induction of neurodegeneration, this study was designed to investigate the effect of PF11 on activated microglia. PF11 significantly suppressed the release of ROS and proinflammatory mediators induced by LPS in a microglial cell line N9 including NO, PGE2, IL-1β, IL-6 and TNF-α. Moreover, PF11 inhibited interaction and expression of TLR4 and MyD88 in LPS-activated N9 cells, resulting in an inhibition of the TAK1/IKK/NF-κB signaling pathway. PF11 also inhibited the phosphorylation of Akt and MAPKs induced by LPS in N9 cells. Importantly, PF11 significantly alleviated the death of SH-SY5Y neuroblastoma cells and primary cortical neurons induced by the conditioned-medium from activated microglia. At last, the effect of PF11 on neuroinflammation was confirmed in vivo: PF11 mitigated the microglial activation and proinflammatory factors expression obviously in both cortex and hippocampus in mice injected intrahippocampally with LPS. These findings indicate that PF11 exerts anti-neuroinflammatory effects on LPS-activated microglial cells by inhibiting TLR4-mediated TAK1/IKK/NF-κB, MAPKs and Akt signaling pathways, suggesting its therapeutic implication for neurodegenerative disease associated with neuroinflammation.
Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, 110016 Shenyang, PR China. Electronic address: xiaoxiao86517@163.com.
Xiaoxiao
X
Wang
Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, 110016 Shenyang, PR China. Electronic address: wcm123_80@yahoo.com.cn.
Chunming
C
Wang
Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, National Cancer Institute at Frederick, National Institutes of Health, USA. Electronic address: wangji@mail.ncifcrf.gov.
Jiming
J
Wang
Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, 110016 Shenyang, PR China. Electronic address: zhaosiqi2010@gmail.com.
Siqi
S
Zhao
Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, 110016 Shenyang, PR China. Electronic address: zhangkuosyphu@163.com.
Kuo
K
Zhang
Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, 110016 Shenyang, PR China. Electronic address: 290686748@qq.com.
Jingmin
J
Wang
Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, 110016 Shenyang, PR China. Electronic address: 798891145@qq.com.
Wei
W
Zhang
Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, 110016 Shenyang, PR China. Electronic address: wucf@syphu.edu.cn.
Chunfu
C
Wu
Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, 110016 Shenyang, PR China. Electronic address: yangjingyu2006@gmail.com.
Jingyu
J
Yang
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects* / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
D000894:Anti-Inflammatory Agents, Non-Steroidal; D036145:Ginsenosides; D008070:Lipopolysaccharides; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D018696:Neuroprotective Agents; D051057:Proto-Oncogene Proteins c-akt; D051197:Toll-Like Receptor 4; D000099151:MAP Kinase Kinase Kinase 7; C495345:TLR4 protein, human; C493487:Tlr4 protein, mouse; C413985:pseudoginsenoside F11
Akt; MAPKs; Microglia; NF-κB; PF11; TLR4