Effect of Leonurus japonicus alkaloids on endometrial inflammation and its mechanisms

The aerial parts of Leonurus japonicus Houtt. (Chinese motherwort) are famous for their efficacy in treating obstetrical and gynecological diseases in traditional Chinese medicine (TCM). Alkaloids are the major bioactive components of motherwort and have gained extensive attention for alleviating several symptoms of obstetrical and gynecological diseases such as postpartum hemorrhage, postpartum rehabilitation, irregular menstruation, and dysmenorrhea. However, the effects of motherwort alkaloids on endometritis remain unclear.

The aim of this study was to investigate the effect of motherwort total alkaloids (MTAs) on endometritis and explore the molecular mechanisms using an integrating network analysis and in vitro experimental verification.

Ultra-high performance liquid chromatography-tandem quadrupole-orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap HRMS) was used to analyze and identify the components in the MTAs. The effects of MTAs were evaluated using bacteria-induced endometritis in rats. Network pharmacology was conducted to predict possible mechanism pathways of MTAs in endometritis. Finally, lipopolysaccharide-stimulated mouse mononuclear macrophage (RAW 264.7) cells and human endometrial epithelial cells were used to identify signaling pathways through which MTAs exert their effects.

Thirty-nine alkaloids were identified in MTAs using the UPLC-Q-Orbitrap HRMS analysis. Their corresponding putative targets were then predicted. The MTAs exerted pharmacological effects on endometritis through a multi-ingredient and multi-target pattern. Network pharmacology showed that the MTAs had 152 candidate targets in treating endometritis. According to the KEGG analysis, the MTAs were found to potentially affect the PI3K-AKT and NF-κB signaling pathways. The following experiments showed that the MTAs exhibited significant effects on endometritis in vivo, significantly reduced the overproduction of inflammatory mediators, and promoted endometrial cell repair via the PI3K/AKT/NF-κB signaling pathway.

Motherwort alkaloids can be used to treat endometrial inflammation by regulating the PI3K/AKT/NF-κB pathway. This study provides a scientific basis for the use of MTAs for treating endometritis.