4.5 Article

SCM-198 ameliorates endometrial inflammation via suppressing the LPS-JNK- cJUN/cFOS-TLR4-NF-κB pathway

期刊

ACTA BIOCHIMICA ET BIOPHYSICA SINICA
卷 53, 期 9, 页码 1207-1215

出版社

SCIENCE PRESS
DOI: 10.1093/abbs/gmab095

关键词

SCM-198; endometritis; cJUN/cFOS; TLR4; NF-kappa B

资金

  1. National Basic Research Program of China [2017YFC1001403]
  2. National Natural Science Foundation of China [31970859, 81630036, 91542116]
  3. International Cooperation Project between Macau and Shanghai [20410760300]
  4. Strategic Collaborative Research Program of the Ferring Institute of Reproductive Medicine - Ferring Pharmaceuticals
  5. Chinese Academy of Sciences [FIRMX200504]
  6. Innovation-oriented Science and Technology Grant from NHC Key Laboratory of Reproduction Regulation [CX2017-2]
  7. Program of Shanghai Academic/Technology Research Leader [17XD1400900]
  8. Innovative Research Team of High-level Local Universities in Shanghai [ZDSYS14005]
  9. Key Laboratory Program of the Education Commission of Shanghai Municipality [ZDSYS14005]

向作者/读者索取更多资源

SCM-198, a synthetic form of leonurine, has been found to possess anti-inflammatory effects and inhibit endometrial inflammation by suppressing the LPS-JNK-cJUN/cFOS-TLR4-NF-kappa B signaling pathway. In vivo studies in a mouse model showed that SCM-198 could be effective in preventing and treating endometritis, whether administered pre-treatment or post-treatment via vaginal or intraperitoneal administration.
Endometritis is an inflammatory disease of the endometrium, which is responsible for endometrial dysfunction, decidualization failure, and increased incidence of early pregnancy loss. SCM-198, a synthetic form of leonurine, is well known to possess anti-inflammatory effects. SCM-198 has been reported to display beneficial effects on endometritis. However, the specific mechanisms of SCM-198 in preventing endometritis remain unknown. In this study, we focused on the molecular mechanism of SCM-198 in inhibiting endometritis. The anti-inflammatory effects and the related signaling pathways of SCM-198 were studied in vitro using human endometrial stromal cells (hESCs). Reverse transcriptase-polymerase chain reaction and western blot analysis results demonstrated that SCM-198 markedly inhibited lipopolysaccharide (LPS)-induced endometrial inflammatory response by suppressing the LPS-JNK-cJUN/cFOS-TLR4-NF-kappa B pathway. The preventive and therapeutic effects of SCM-198 on endometrial inflammation were explored by using a mouse model of LPS-induced endometritis. SCM-198 produced essentially the same effects when administered either post-treatment (after LPS) or pre-treatment (before LPS) via vaginal or intraperitoneal administration. In vivo results indicated that SCM-198 is a potential effective drug for the treatment of endometritis.

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