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

Jul 14, 2021Acta biochimica et biophysica Sinica

SCM-198 reduces uterine inflammation by blocking a specific immune signaling pathway

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Abstract

SCM-198 significantly inhibited the endometrial inflammatory response induced by lipopolysaccharide (LPS).

SCM-198 may prevent endometritis by targeting the LPS-JNK-cJUN/cFOS-TLR4-NF-κB signaling pathway.
The anti-inflammatory effects of SCM-198 were confirmed in human endometrial stromal cells (hESCs) in vitro.
In a mouse model of LPS-induced endometritis, SCM-198 demonstrated both preventive and therapeutic effects.
Administering SCM-198 either before or after LPS treatment resulted in similar effectiveness.

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

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