Geniposide plays an anti-inflammatory role via regulating TLR4 and downstream signaling pathways in lipopolysaccharide-induced mastitis in mice.
Geniposide is a medicine isolated from Gardenia jasminoides Ellis, which is a traditional Chinese herb that is widely used in Asia for the treatment of inflammation, brain diseases, and hepatic disorders. Mastitis is a highly prevalent and important infectious disease. In this study, we used a lipopolysaccharide (LPS)-induced mouse mastitis model and LPS-stimulated primary mouse mammary epithelial cells (mMECs) to explore the anti-inflammatory effect and the mechanism of action of geniposide. Using intraductal injection of LPS as a mouse model of mastitis, we found that geniposide significantly reduced the infiltration of inflammatory cells and downregulated the production of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). To further investigate the anti-inflammatory mechanism, we used LPS-stimulated mMECs as an in vitro mastitis model. The results of enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR) showed that geniposide inhibited the expression of TNF-α, IL-1β, and IL-6 in a dose-dependent manner. Western blot analysis demonstrated that geniposide could suppress the phosphorylation of inhibitory kappa B (IκBα), nuclear factor-κB (NF-κB), p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). Geniposide also inhibited the expression of toll-like receptor 4 (TLR4) in the LPS-stimulated mMECs. In conclusion, geniposide exerted its anti-inflammatory effect by regulating TLR4 expression, which affected the downstream NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways. Thus, geniposide may be a potential drug for mastitis therapy.
College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, 130062, People's Republic of China.
Xiaojing
X
Song
Wen
W
Zhang
Tiancheng
T
Wang
Haichao
H
Jiang
Zecai
Z
Zhang
Yunhe
Y
Fu
Zhengtao
Z
Yang
Yongguo
Y
Cao
Naisheng
N
Zhang
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D005260:Female; D039823:Iridoids / Q000494:pharmacology / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D008413:Mastitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D000893:Anti-Inflammatory Agents; D039823:Iridoids; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C007835:geniposide