Magnesium Lithospermate B Protects Neurons Against Amyloid β (1-42)-Induced Neurotoxicity Through the NF-κB Pathway.
Magnesium lithospermate B (MLB) is one of the major bioactive components of Radix Salviae miltiorrhizae, a Chinese traditional herbal medicine colloquially known as Dan Shen. In this study, we investigated the neuroprotective effect of MLB against oligomeric amyloid β (Aβ) (1-42)-induced neurotoxicity in cultured FVB mouse hippocampal neurons. We found that pretreatment with MLB not only prevents a loss in neuronal cell viability following exposure to Aβ (1-42), but also attenuates Aβ (1-42)-induced release of pro-inflammatory cytokines and neuronal apoptosis in a dose-dependent manner. Mechanistic studies show that MLB counteracts Aβ (1-42)-induced activation of the nuclear factor kappa B (NF-κB) pathway, evidenced by the suppression of NF-κB luciferase reporters, decreased expression of phosphorylated Inhibitor κB α and IκB kinase α, and reduced nuclear translocation of p65 in response to pre-treatment with 50 μg/ml MLB prior to Aβ (1-42) exposure. MLB was able to reverse the increase in phosphorylated c-Jun N-terminal kinase (JNK) levels as well as the decrease in phosphorylated Akt levels that are induced by Aβ (1-42), although this finding did not extend to extracellular signal-regulated kinase or p38 kinases. Furthermore, combining MLB with the JNK inhibitor SP600125 synergistically counteracts the Aβ (1-42)-induced reduction in cell viability and neurite growth, and the neuroprotective effects of MLB could be attenuated by the Akt inhibitor triciribine. In conclusion, these results suggest that MLB can protect against Aβ (1-42)-induced neuronal damage, which is most likely to be mediated by the NK-κB pathway.
Department of Neurology and Neurosurgery, Zhangjiagang First People's Hospital (Zhangjiagang Hospital Affiliated to Soochow University), No. 68 Jiyang West Road, Zhangjiagang City, 215600, Jiangsu Province, People's Republic of China.
Feng
F
Jiang
Yongqiang
Y
Mao
Huixiang
H
Liu
Ping
P
Xu
Li
L
Zhang
Xiaobo
X
Qian
Xiaofeng
X
Sun
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004789:Enzyme Activation; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects*; D010446:Peptide Fragments / Q000633:toxicity*
D016229:Amyloid beta-Peptides; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C061091:lithospermate B; D048670:MAP Kinase Kinase 4