Anti-inflammatory effects of novel <i>polygonum multiflorum</i> compound via inhibiting NF-κB/MAPK and upregulating the Nrf2 pathways in LPS-stimulated microglia

다국어 초록 (Multilingual Abstract)

<P><B>Abstract</B></P> <P>The incorporation of <I>Polygonum multiflorum</I> into the diet can result in anti-aging effects owing to its wide range of biological and pharmaceutical properties. We investigated the anti-neuroinflammatory properties of CRPE56IGIH isolated from <I>P. multiflorum</I> by focusing on its role in the induction of phase II antioxidant enzymes and the modulation of upstream signaling pathways. In microglia, CRPE56IGIH significantly inhibited lipopolysaccharide (LPS)-stimulated nitric oxide and prostaglandin E<SUB>2</SUB> production with nonspecific cytotoxicity. CRPE56IGIH also markedly inhibited LPS-inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 protein and mRNA expression in the same manner as it inhibited nitric oxide and prostaglandin E<SUB>2</SUB> production. In the control cells, NF-κB transactivation and nuclear translocation occurred at a baseline level, which was significantly increased in response to LPS. However, pretreatment with CRPE56IGIH concentration-dependently inhibited the LPS-induced NF-κB transactivation and nuclear translocation. The phosphorylation of Janus kinase-signal transducers and activators of transcription and mitogen-activated protein kinases was markedly upregulated by LPS, but considerably and dose-dependently inhibited by pretreatment with CRPE56IGIH. Furthermore, CRPE56IGIH induced the expression of phase II antioxidant enzymes, including heme oxygenase-1 (HO-1) and NADPH dehydrogenase quinone-1 (NQO-1). The activation of upstream signaling pathways, such as the Nrf2 pathway, was significantly increased following CRPE56IGIH treatment. Furthermore, the anti-neuroinflammatory effect of CRPE56IGIH was reversed by transfection of Nrf2, HO-1, and NQO-1 siRNA. Our results indicated that CRPE56IGIH isolated from <I>P. multiflorum</I> could be used as a natural anti-neuroinflammatory agent that induces phase II antioxidant enzymes <I>via</I> Nrf2 signaling.</P> <P><B>Highlights</B></P> <P> <UL> <LI> CRPE56IGIH is a natural compound isolated from <I>Polygonum multiflorum.</I>. </LI> <LI> CRPE56IGIH inhibits LPS induced neuroinflammatory response in microglia. </LI> <LI> CRPE56IGIH inhibits LPS-induced NF-κB and JAK-STATs activation in microglia. </LI> <LI> Nrf2 mediates the anti-neuroinflammation of CRPE56IGIH in microglia. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>