The active components and potential mechanisms of Li-Chong-Xiao-Zhen granules in the treatment of ovarian cancer: An integrated metabolomics, proteomics, network pharmacology and experimental validation

IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Journal of ethnopharmacology Pub Date : 2025-02-10 DOI:10.1016/j.jep.2025.119474
Yiliu Chen , Ran Su , Yunguang Hu , Jiali Luo , Chu Yi , Yinbin Zhu , Qing Feng , Xianxin Yan , Min Ma , Weifeng Feng
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Abstract

Ethnopharmacological relevance

Li-Chong-Xiao-Zhen granules (LCXZG) has the effect of " activate blood and resolve stasis," " soften hardness and dissipate binds " properties, and was widely used in the clinic for decades to treat uterine fibroids and ovarian cancer (OC), which is called "zheng jia" in traditional Chinese medicine.

Aim of the study

The aim of this study is to identify the active components of LCXZG and elucidate the mechanism of LCXZG in ovarian cancer by combining network pharmacology, metabolomics and proteomics.

Material and methods

The absorbed compounds in serum of LCXZG was identified by liquid chromatography-mass spectrometry. Network pharmacology was used to predict the active components and target genes of LCXZG. The therapy mechanism of LCXZG on OC were determined by establishing a nude mouse xenograft tumor model and using combined metabolomics and proteomics analysis.

Results

A total of 218 absorbed compounds in serum of LCXZG were identified by UPLC-MS. Network pharmacology results showed that lipid and atherosclerosis, chemical carcinoma-receptor activation and PI3K-AKT signaling were potential target pathways of LCXZG in the treatment of OC. Further metabolomics and proteomics studies demonstrated that LCXZG altered glycerophospholipid metabolism in ovarian cancer.

Conclusions

This study demonstrated that most of the active Compound of LCXZG are Paeoniflorin, Turanose, Amygdalin and Benzoylpaeoniflorin, which may exert their anti-tumor effects by regulating glycerophospholipid metabolism in ovarian cancer.

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利冲消震颗粒治疗卵巢癌的有效成分及其作用机制:综合代谢组学、蛋白质组学、网络药理学和实验验证。
民族药理学相关性:利冲消震颗粒(LCXZG)具有“活血化瘀”、“柔硬散粘”的功效,几十年来在临床上被广泛应用于治疗子宫肌瘤和卵巢癌(OC),在中医中被称为“正佳”。研究目的:本研究旨在结合网络药理学、代谢组学和蛋白质组学,鉴定LCXZG的有效成分,阐明LCXZG在卵巢癌中的作用机制。材料与方法:采用液相色谱-质谱联用法对LCXZG血清中吸收成分进行鉴定。采用网络药理学方法对其活性成分和靶基因进行预测。通过建立裸鼠异种移植瘤模型,结合代谢组学和蛋白质组学分析,确定LCXZG对OC的治疗机制。结果:用UPLC-MS鉴别出了218种吸收成分。网络药理学结果显示,脂质与动脉粥样硬化、化学癌受体激活、PI3K-AKT信号通路是LCXZG治疗OC的潜在靶点通路。进一步的代谢组学和蛋白质组学研究表明,LCXZG改变了卵巢癌患者的甘油磷脂代谢。结论:本研究表明,LCXZG的主要活性成分为芍药苷、蔗糖、苦杏仁苷和苯甲酰芍药苷,其抗肿瘤作用可能是通过调节卵巢癌组织的甘油磷脂代谢来发挥的。
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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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