Chemical Constituents and an Antineuroinflammatory Lignan, Savinin from the Roots of Acanthopanax henryi

Li, Xiao-Jun; Kim, Kwan-Woo; Oh, Hyuncheol; Liu, Xiang-Qian; Kim, Youn-Chul

MAPKs are a family of serine/threonine protein kinases, and they consist of three major subunits: p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). MAPKs are involved in various cellular processes, including proliferation, differentiation, stress responses, and immune responses [33] . In inflammatory responses, the activation of MAPKs leads to release of inflammatory-related factors, such as iNOS, COX-2, ILs, and TNF- [34] . Therefore, we further investigated whether the antineuroinflammatory effects of compound in LPS-stimulated BV2 microglial cells were related to the inactivation of MAPKs. Our results showed that compound significantly inhibited the phosphorylation of p38 MAPK, but it did not affect the phosphorylation of ERK and JNK MAPKs. Nuclear factor kappa B (NF-B) is one of the major transcription factors regulating inflammatory responses. When microglial cells are stimulated with ILs, TNF-, interferons, or LPS, NF-B can be activated following increased translocation of p65 and p50, which are subunits of the NF-B dimer, into the nucleus, as well as the phosphorylation and degradation of inhibitor of kappa B (I B)-in the cytosol [35] . This response upregulates the expression of proinflammatory cytokines, chemokines, and adhesion molecules in microglial cells [1] . Therefore, NF-B can be an important target for the treatment of neuroinflammation-related neurodegenerative diseases. Interestingly, pretreatment with compound did not decrease the nuclear translocation of p65 and p50 or the phosphorylation and degradation of I B-(data not shown). Considering the effect of compound on the LPS-induced activation of NF-B and MAPK pathways, it is suggested that compound exerted antineuroinflammatory effects by specifically inactivating the p38 MAPK pathway.