title: Malloapelta B suppresses LPS-induced NF-κB activation and NF-κB-regulated target gene products.
abstract: Nuclear factor-κB (NF-κB) and the signaling pathways that regulate its activity have become a focal point for intense drug research and development efforts. NF-κB regulates the transcription of a large number of genes, particularly those involved in immune, inflammatory, and anti-apoptotic responses. In our search for NF-κB inhibitors from natural resources, we identified malloapelta B as an inhibitor of NF-κB activation from Mallotus apelta Muell-Arg. In the present study, we demonstrated the effect of malloapelta B on NF-κB activation in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. This compound suppressed NF-κB activation through the inhibition of IκB kinase (IKK) activation, thereby blocking the phosphorylation and degradation of the inhibitor of NF-κB alpha (IκBα), and the nuclear translocation and DNA-binding activity of p65. The suppression of NF-κB by malloapelta B led to the down-regulation of target genes involved in inflammation and proliferation. Taken together, this study extends our understanding on the mechanisms underlying the possible anti-inflammatory and anti-cancer activities of malloapelta B. Our findings provide new insight into its mechanisms of action and propose a potential application of malloapelta B for inflammatory diseases as well as certain cancers associated with abnormal NF-κB activation.
authors.affiliation: Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China; Molecular Cancer Research Center, Yanbian University, Yanji 133002, Jilin Province, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Ma
authors.affiliation: Molecular Cancer Research Center, Yanbian University, Yanji 133002, Jilin Province, China; Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Department of Chemistry, Yanbian University, Yanji 133002, Jilin Province, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Shi
authors.affiliation: Molecular Cancer Research Center, Yanbian University, Yanji 133002, Jilin Province, China; Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Department of Chemistry, Yanbian University, Yanji 133002, Jilin Province, China.
authors.forename: Chunliu
authors.initials: C
authors.lastname: Mi
authors.affiliation: Department of Pharmacy, Yanbian the Second People Hospital, Yanji 133000, Jilin Province, China.
authors.forename: Hong Lan
authors.initials: HL
authors.lastname: Li
authors.affiliation: Molecular Cancer Research Center, Yanbian University, Yanji 133002, Jilin Province, China. Electronic address: jjlee0908@gmail.com.
authors.forename: Jung Joon
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China; Molecular Cancer Research Center, Yanbian University, Yanji 133002, Jilin Province, China. Electronic address: xjjin@ybu.edu.cn.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Jin
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation / Q000235:genetics; D007249:Inflammation / Q000235:genetics; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D036461:Mallotus Plant / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport; D051996:Transcription Factor RelA / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D001578:Benzopyrans; D008070:Lipopolysaccharides; D016328:NF-kappa B; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; C517306:malloapelta B
keywords: Inflammation; IκBα; Malloapelta B; Nuclear factor-κB (NF-κB); Proliferation