title: HJB-1, a 17-hydroxy-jolkinolide B derivative, inhibits LPS-induced inflammation in mouse peritoneal macrophages.
abstract: Jolkinolide B (JB) and 17-hydroxy-JB (HJB) are diterpenoids from plants and it has been reported that the presence of a C-17 hydroxy group in JB significantly enhances the anti-inflammatory potency of JB. In this study, two HJB derivatives HJB-1 and HJB-2 were generated by the chemical modification of a 17-hydroxy group of HJB. HJB-1 more effectively inhibited TNF-α, IL-1β and IL-6 release in LPS-stimulated mouse peritoneal macrophages. In addition, HJB-1 reduced LPS-induced mRNA expression of TNF-α, IL-1β, IL-6, COX-2 and iNOS in a concentration-dependent manner, but did not alter IL-10 mRNA expression. LPS-induced NF-κB activation and MAPK phosphorylation were also effectively inhibited by HJB-1. These results demonstrate that HJB-1 exerts anti-inflammatory effects on LPS-activated mouse peritoneal macrophages by inhibiting NF-κB activation and MAPK phosphorylation and modification of a 17-hydroxy group of HJB may enhance the anti-inflammatory potency of HJB derivatives.
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, PR China.
authors.forename: Lei-Chang
authors.initials: LC
authors.lastname: Pan
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, PR China; School of Life Sciences and Technology, Tongji University, Shanghai 200092, PR China.
authors.forename: Xiao-Han
authors.initials: XH
authors.lastname: Xu
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, PR China.
authors.forename: Na-Na
authors.initials: NN
authors.lastname: Zhang
authors.affiliation: Central Laboratory, The Second Clinical Hospital, Jilin University, Changchun 130041, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.affiliation: Jilin Provincial Center for Disease Control and Prevention, 130062, PR China.
authors.forename: Dong-Lin
authors.initials: DL
authors.lastname: Wu
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, PR China.
authors.forename: Qi-Sheng
authors.initials: QS
authors.lastname: Peng
authors.affiliation: Dept. of Biomedical Sciences, Ross University School of Veterinary Medicine, Saint Kitts and Nevis.
authors.forename: Michel
authors.initials: M
authors.lastname: Vandenplas
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai 200092, PR China. Electronic address: hbwang@tongji.edu.cn.
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Wang
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, PR China. Electronic address: wanchunsun@jlu.edu.cn.
authors.forename: Wan-Chun
authors.initials: WC
authors.lastname: Sun
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D004224:Diterpenes; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C057914:jolkinolide B; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases
keywords: 17-Hydroxy-jolkinolide B; Inflammation; LPS; MAPK; NF-κB