title: Geniposide, from Gardenia jasminoides Ellis, inhibits the inflammatory response in the primary mouse macrophages and mouse models.
abstract: Geniposide, a main iridoid glucoside component of gardenia fruit, has been known to exhibit antibacterial, anti-inflammatory and other important therapeutic activities. The objective of this study was to investigate the protective effects of geniposide on inflammation in lipopolysaccharide (LPS) stimulated primary mouse macrophages in vitro and LPS induced lung injury model in vivo. The expression of pro-inflammatory cytokines was determined by enzyme-linked immunosorbent assay (ELISA). Nuclear factor-kappa B (NF-κB), inhibitory kappa B (IκBα) protein, p38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and Toll-like receptor 4 (TLR4) were determined by Western blot. Further analysis was carried out in mTLR4 and mMD-2 co-transfected HEK293 cells. The results showed that geniposide markedly inhibited the LPS-induced TNF-α, IL-6 and IL-1β production both in vitro and in vivo. Geniposide blocked the phosphorylation of IκBα, p65, p38, ERK and JNK in LPS stimulated primary mouse macrophages. Furthermore, geniposide inhibited the expression of TLR4 in LPS stimulated primary mouse macrophages and inhibited the LPS-induced IL-8 production in HEK293-mTLR4/MD-2 cells. In vivo study, it was also observed that geniposide attenuated lung histopathologic changes in the mouse models. These results suggest that geniposide exerts an anti-inflammatory property by down-regulating the expression of TLR4 up-regulated by LPS. Geniposide is highly effective in inhibiting acute lung injury and may be a promising potential therapeutic reagent for acute lung injury treatment.
authors.affiliation: Department of Clinical Veterinary Medicine, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China.
authors.forename: Yunhe
authors.initials: Y
authors.lastname: Fu
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Jinhua
authors.initials: J
authors.lastname: Liu
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Dejie
authors.initials: D
authors.lastname: Liang
authors.forename: Fengyang
authors.initials: F
authors.lastname: Li
authors.forename: Depeng
authors.initials: D
authors.lastname: Li
authors.forename: Yongguo
authors.initials: Y
authors.lastname: Cao
authors.forename: Xichen
authors.initials: X
authors.lastname: Zhang
authors.forename: Naisheng
authors.initials: N
authors.lastname: Zhang
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002478:Cells, Cultured; D005260:Female; D032062:Gardenia / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000502:physiology; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics; D007377:Interleukin-3 / Q000235:genetics; D039823:Iridoids / Q000737:chemistry / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000235:genetics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007377:Interleukin-3; D039823:Iridoids; D011993:Recombinant Fusion Proteins; C404145:myelopoietin; D016179:Granulocyte Colony-Stimulating Factor; C007835:geniposide