title: Geniposide inhibited lipopolysaccharide-induced apoptosis by modulating TLR4 and apoptosis-related factors in mouse mammary glands.
abstract: OBJECTIVE
  Geniposide, a major iridoid glycoside found in gardenia fruit, is widely used in Asian countries for its anti-inflammatory, anti-tumor and anti-apoptotic activities. Although the anti-inflammatory effect of geniposide has been widely reported, its anti-apoptotic role in mastitis remains unclear. In the present study, we investigated whether geniposide exerts anti-apoptotic activity in lipopolysaccharide (LPS)-induced mouse mammary glands.
  
  
  METHODS
  We established a LPS-induced mouse mastitis model and LPS-stimulated primary mouse mammary epithelial cells (mMECs) model to investigate the anti-apoptotic effect of geniposide and the underlying mechanism of action. In the in vivo studies, apoptosis in mammary glands was detected by TUNEL. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to analyze the expression of Bax, Bcl-2, Caspase-3 and p53. In the in vitro study, the apoptosis in mammary epithelial cells was measured by Live-Dead staining. Western blot and qRT-PCR analysis were used to analyze the expression of Bax, Bcl-2, Caspase-3, p53 and TLR4.
  
  
  RESULTS
  Geniposide alleviated mammary gland apoptosis, down-regulated Bax expression, inhibited Caspase-3 cleavage and p53 phosphorylation and up-regulated Bcl-2 expression in vivo. In vitro, geniposide decreased the ratio of dead cells in a dose-dependent manner. Geniposide inhibited Bax expression and Caspase-3 cleavage, and up-regulated the expression of Bcl-2. Moreover, geniposide down-regulated the expression of TLR4 and repressed the phosphorylation of p53.
  
  
  CONCLUSIONS
  These results demonstrate that the anti-apoptotic property of geniposide is due to its modulation of TLR4 and apoptosis-related factors (p53, Bax, Bcl-2 and Caspase-3) in LPS-induced mouse mastitis.
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Song
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China.
authors.forename: Mengyao
authors.initials: M
authors.lastname: Guo
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China.
authors.forename: Tiancheng
authors.initials: T
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China. Electronic address: ygcao82@gmail.com.
authors.forename: Yongguo
authors.initials: Y
authors.lastname: Cao
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China. Electronic address: zhangns@jlu.edu.cn.
authors.forename: Naisheng
authors.initials: N
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D032062:Gardenia / Q000737:chemistry; D039823:Iridoids / Q000737:chemistry / Q000627:therapeutic use*; D008070:Lipopolysaccharides; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008413:Mastitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D051197:Toll-Like Receptor 4 / Q000276:immunology*
chemical_list: D000893:Anti-Inflammatory Agents; D039823:Iridoids; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; C007835:geniposide
keywords: Apoptosis; Geniposide; Lipopolysaccharide (LPS); Mastitis; Toll-like receptor 4