Effect of Leonurus japonicus alkaloids on endometrial inflammation and its mechanisms

IF 5.4 2区医学 Q1 CHEMISTRY, MEDICINAL Journal of ethnopharmacology Pub Date : 2025-02-27 Epub 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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益母草生物碱对子宫内膜炎症的影响及其机制。

益母草地上部分的民族药理学意义。益母草（中国益母草）以其治疗妇产科疾病的功效而闻名于世。生物碱是益母草的主要生物活性成分，因缓解产后出血、产后康复、月经不调、痛经等多种妇产科疾病的症状而受到广泛关注。然而，益母草生物碱对子宫内膜炎的作用尚不清楚。研究目的：采用综合网络分析和体外实验验证的方法，探讨益母草总生物碱（mta）对子宫内膜炎的作用，并探讨其分子机制。材料与方法：采用超高效液相色谱-串联四极杆-轨道rap高分辨率质谱法（UPLC-Q-Orbitrap HRMS）对mta中的成分进行分析鉴定。用细菌诱导的大鼠子宫内膜炎来评价mta的作用。采用网络药理学方法预测mta在子宫内膜炎中的可能机制途径。最后，利用脂多糖刺激小鼠单核巨噬细胞（RAW 264.7）细胞和人子宫内膜上皮细胞来鉴定mta发挥作用的信号通路。结果：通过UPLC-Q-Orbitrap HRMS分析，共鉴定出39种生物碱。然后预测它们相应的假定目标。mta通过多成分、多靶点模式对子宫内膜炎发挥药理作用。网络药理学显示mta治疗子宫内膜炎有152个候选靶点。根据KEGG分析，发现mta可能影响PI3K-AKT和NF-κB信号通路。随后的实验表明，mta在体内对子宫内膜炎有显著的治疗作用，可显著减少炎症介质的过量产生，并通过PI3K/AKT/NF-κB信号通路促进子宫内膜细胞修复。结论：益母草生物碱可通过调节PI3K/AKT/NF-κB通路治疗子宫内膜炎症。本研究为mta治疗子宫内膜炎提供了科学依据。

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来源期刊

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.