title: Artemisinin inhibits inflammatory response via regulating NF-κB and MAPK signaling pathways.
abstract: Artemisinin, isolated from the Chinese plant Artemisia annua, has been used for many years to treat different forms of malarial parasites. In this study, we explored the anti-inflammatory activity of artemisinin and the underlying mechanism of this action. We demonstrated that the anti-inflammatory effects of artemisinin in TPA-induced skin inflammation in mice. Then the artemisinin significantly inhibited the expression of NF-κB reporter gene induced by TNF-α in a dose-dependent manner. Artemisinin also inhibited TNF-α induced phosphorylation and degradation of IκBα, p65 nuclear translocation. Artemisinin also has an impact on upstream signaling of IKK through the inhibition of expression of adaptor proteins, TNF receptor-associated factor 2 (TRAF2) and receptor interacting protein 1 (RIP1). Furthermore, pretreatment of cells with artemisinin prevented the TNF-α-induced expression of NF-κB target genes, such as anti-apoptosis (c-IAP1, Bcl-2, and FLIP), proliferation (COX-2, cyclinD1), invasion (MMP-9), angiogenesis (VEGF), and major inflammatory cytokines (TNF-α, iNOS, and MCP1). We also proved that artemisinin potentiated TNF-α-induced apoptosis. Moreover, artemisinin significantly impaired the ROS production and phosphorylation of p38 and ERK, but did not affect the phosphorylation of JNK. Taken together, artemisinin may be a potentially useful therapeutic agent for inflammatory-related diseases.
authors.affiliation: a Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Molecular Cancer Research Center, College of Pharmacy , Yanbian University , Yanji, Jilin Province , China.
authors.forename: Ke Si
authors.initials: KS
authors.lastname: Wang
authors.affiliation: a Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Molecular Cancer Research Center, College of Pharmacy , Yanbian University , Yanji, Jilin Province , China.
authors.forename: Junbo
authors.initials: J
authors.lastname: Li
authors.affiliation: a Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Molecular Cancer Research Center, College of Pharmacy , Yanbian University , Yanji, Jilin Province , China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: a Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Molecular Cancer Research Center, College of Pharmacy , Yanbian University , Yanji, Jilin Province , China.
authors.forename: Chunliu
authors.initials: C
authors.lastname: Mi
authors.affiliation: a Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Molecular Cancer Research Center, College of Pharmacy , Yanbian University , Yanji, Jilin Province , China.
authors.forename: Juan
authors.initials: J
authors.lastname: Ma
authors.affiliation: a Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Molecular Cancer Research Center, College of Pharmacy , Yanbian University , Yanji, Jilin Province , China.
authors.forename: Lian Xun
authors.initials: LX
authors.lastname: Piao
authors.affiliation: a Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Molecular Cancer Research Center, College of Pharmacy , Yanbian University , Yanji, Jilin Province , China.
authors.forename: Guang Hua
authors.initials: GH
authors.lastname: Xu
authors.affiliation: a Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Molecular Cancer Research Center, College of Pharmacy , Yanbian University , Yanji, Jilin Province , China.
authors.forename: Xuezheng
authors.initials: X
authors.lastname: Li
authors.affiliation: a Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Molecular Cancer Research Center, College of Pharmacy , Yanbian University , Yanji, Jilin Province , China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Jin
mesh_terms: D000818:Animals; D037621:Artemisinins / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000276:immunology*; D028861:Nuclear Pore Complex Proteins / Q000276:immunology; D016601:RNA-Binding Proteins / Q000276:immunology; D047990:TNF Receptor-Associated Factor 1 / Q000276:immunology; D047992:TNF Receptor-Associated Factor 2 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects / Q000494:pharmacology
chemical_list: C119724:AGFG1 protein, human; D037621:Artemisinins; D016328:NF-kappa B; D028861:Nuclear Pore Complex Proteins; D016601:RNA-Binding Proteins; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2; D014409:Tumor Necrosis Factor-alpha; C031327:artemisinin
keywords: Artemisinin; Inflammation; IκBα; MAPK; Nuclear factor-κB (NF-κB)