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

• Published in: Acta biochimica et biophysica Sinica Vol. 53; no. 9; pp. 1207 - 1215
• Main Authors: Lin, Yikong, Li, Yunyun, Li, Xinyi, Liu, Xinhua, Wang, Xiaolin, Yu, Min, Zhu, Yizhun, Du, Meirong
• Format: Journal Article
• Language: English
• Published: UK Oxford University Press 01.09.2021
• Subjects: Adult; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Cytokines - metabolism; Endometritis - chemically induced; Endometritis - pathology; Endometritis - prevention & control; Endometrium - drug effects; Epithelial Cells - drug effects; Female; Gallic Acid - analogs & derivatives; Gallic Acid - pharmacology; Gallic Acid - therapeutic use; Humans; Lipopolysaccharides - toxicity; MAP Kinase Signaling System - drug effects; Mice; Mice, Inbred C57BL; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; Proto-Oncogene Proteins c-fos - metabolism; Proto-Oncogene Proteins c-jun - metabolism; Signal Transduction - drug effects; Stromal Cells - drug effects; Toll-Like Receptor 4 - antagonists & inhibitors; Toll-Like Receptor 4 - metabolism; NF-κB; endometritis; cFOS; SCM-198; TLR4; cJUN
• ISSN: 1672-9145; 1745-7270
• DOI: 10.1093/abbs/gmab095

Abstract 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.