title: Novel compound from Polygonum multiflorum inhibits inflammatory response in LPS-stimulated microglia by upregulating AMPK/Nrf2 pathways.
abstract: Polygonum multiflorum extracts are known to improve memory and learning ability, and have neuroprotective and anti-aging activity. However, its function and the underlying mechanisms in neuroinflammation-mediated neurodegenerative disease remain poorly understood. In the present study, we investigated the anti-neuroinflammatory effects of several compounds from P. multiflorum, and found a novel compound, CRPE55IB. The CRPE55IB-induced suppression of NO and PGE2production correlated with inhibition of iNOS and COX-2 protein expression and promoter activity in lipopolysaccharide (LPS)-stimulated microglia. CRPE55IB also reduced the production of pro-inflammatory cytokines (TNF-α and IL-6) induced by LPS. Furthermore, investigation of the molecular mechanism indicated that CRPE55IB inhibited LPS-induced NF-κB activation by inactivating phosphorylation of IKKα/β, and phosphorylation and degradation of IκBα. We further found that CRPE55IB inhibited the phosphorylation of ERK and JNK at a lower concentration than that for p38 MAPK. Further experiments revealed that CRPE55IB treatment considerably increased the activation of Nrf2/ARE, and the expression of its target genes, including HO-1 and NQO1. Moreover, the Knockdown of Nrf2, HO-1, and NQO1 by siRNA abrogated the inhibitory effect of CRPE55IB on iNOS and COX-2 promoter activity. CRPE55IB also induced phosphorylation of AMPK/LKB/CaMKII in microglia. Analysis using a specific inhibitor of AMPK demonstrated that AMPK activation was involved in CRPE55IB-induced HO-1 and NQO1 expression. In addition, the CRPE55IB-induced anti-neuroinflammatory effect was abrogated by a specific inhibitor of AMPK, indicating the important role of AMPK in CRPE55IB-induced anti-neuroinflammation. Collectively, these results demonstrate that CRPE55IB exerts anti-neuroinflammatory effects against LPS via the Nrf2/AMPK signaling pathways.
authors.affiliation: Bio-IT Fusion Technology Research Institute, Pusan National University, Busan, 609-735, Republic of Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Bio-IT Fusion Technology Research Institute, Pusan National University, Busan, 609-735, Republic of Korea.
authors.forename: Mei Ling
authors.initials: ML
authors.lastname: Jin
authors.affiliation: Bio-IT Fusion Technology Research Institute, Pusan National University, Busan, 609-735, Republic of Korea.
authors.forename: Seon Yeong
authors.initials: SY
authors.lastname: Chae
authors.affiliation: Department of Nanomaterials Engineering, Pusan National University, Busan, 609-735, Republic of Korea.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Ko
authors.affiliation: Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Republic of Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Department of Nanomaterials Engineering, Pusan National University, Busan, 609-735, Republic of Korea. Electronic address: gtpark@pusan.ac.kr.
authors.forename: Geuntae
authors.initials: G
authors.lastname: Park
authors.affiliation: Department of Horticultural Bioscience, Pusan National University, Miryang, 627-706, Republic of Korea. Electronic address: ywchoi@pusan.ac.kr.
authors.forename: Young-Whan
authors.initials: YW
authors.lastname: Choi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D000068676:Fallopia multiflora / Q000737:chemistry*; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects*; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051546:Cyclooxygenase 2; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Anti-neuroinflammation; Microglia; Nrf2; Polygonum multiflorum