Effect of Leonurus japonicus alkaloids on endometrial inflammation and its mechanisms

IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Journal of ethnopharmacology Pub Date : 2025-02-02 DOI:10.1016/j.jep.2025.119432
Ou Dai , Yunqiu Fan , Qinmei Zhou , Juanru Liu , Jing Zuo , Fang Wang , Lei Li , Fei Wang , Liang Xiong
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Abstract

Ethnopharmacological relevance

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.

Aim of the study

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.

Materials and methods

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.

Results

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.

Conclusions

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.

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来源期刊
Journal of ethnopharmacology
Journal of ethnopharmacology 医学-全科医学与补充医学
CiteScore
10.30
自引率
5.60%
发文量
967
审稿时长
77 days
期刊介绍: The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.
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