title: Sarsasapogenin-AA13 inhibits LPS-induced inflammatory responses in macrophage cells in vitro and relieves dimethylbenzene-induced ear edema in mice.
abstract: Sarsasapogenin-AA13 (AA13) is a novel synthetic derivative of sarsasapogenin extracted from the Chinese herb Rhizoma Anemarrhenae. In this study we investigated the effects of AA13 on lipopolysaccharide (LPS)-induced production of inflammatory factors in macrophage cells and the anti-inflammatory activity of AA13 in an inflammatory model of dimethylbenzene-induced ear edema. Macrophage cells (RAW264.7 cells and mouse peritoneal macrophages) were exposed to LPS (1 μg/mL); pretreatment with AA13 (5-20 μmol/L) dose-dependently inhibited LPS-induced production of NO, TNF-α and PGE2, and LPS-stimulated expression levels of COX-2 and iNOS. Furthermore, pretreatment with AA13 dose-dependently suppressed LPS-stimulated phosphorylation of p38 and JNK, but had no effect on ERK in RAW264.7 cells. Moreover, pretreatment with AA13 inhibited LPS-induced activation of the nuclear factor (NF)-κB in RAW264.7 cells. The in vivo anti-inflammatory activity of AA13 was demonstrated in a mouse inflammatory model: pre-treatment with either AA13 (20 mg·kg-1·d-1, ig) or a positive control antifani (10 mg·kg-1·d-1, ig) for 3 d significantly relieved dimethylbenzene-induced ear edema. Our results demonstrate that AA13 effectively inhibit LPS-induced inflammatory responses in macrophage cells in vitro and relieve dimethylbenzene-induced ear edema in vivo.
authors.affiliation: Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Dong
authors.affiliation: Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Nan-Nan
authors.initials: NN
authors.lastname: Zhou
authors.affiliation: Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Rui-Xuan
authors.initials: RX
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Jia-Wei
authors.initials: JW
authors.lastname: Xiong
authors.affiliation: Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Pan
authors.affiliation: Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Si-Qi
authors.initials: SQ
authors.lastname: Sun
authors.affiliation: Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Ma
authors.affiliation: Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008813:Mice, Inbred ICR; D014992:Xylenes / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D014992:Xylenes