基于多组学、网络药理学和实验验证探讨苗药七椒生白胶囊治疗白细胞减少症的作用机制

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-06-05 DOI:10.1016/j.phymed.2025.156935

Wei Hu , Chen Li , Chenguang Wang , Wei Liu , Chuntong Li , Lihua Mu , Kun Wang , Mengli Chen

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引用次数: 0

摘要

白细胞减少症是由多种因素引起的，现代药物治疗有明显的副作用，七角生白胶囊（QJSB）是由苗药发展而来的复方方剂，广泛用于临床治疗白细胞减少症。然而，其治疗白细胞减少的作用机制尚不清楚。目的探讨芪jsb治疗白细胞减少症的有效成分、作用及机制。材料与方法本研究采用UPLC-Q-Qrbitrap HRMS技术对青芪皂苷的化学成分和血清成分进行鉴定。利用转录组学分析和网络药理学分析相结合的方法，破译了QJSB的潜在抗白细胞减少机制和关键成分。最后，通过体内实验验证QJSB在环磷酰胺诱导的大鼠白细胞减少模型中关键靶点的表达及干预作用。结果共鉴定出51种化学成分，血清中鉴定出58种化学成分。网络药理学分析表明，QJSB的关键成分为金木黄酮、槲皮素、5,6,7-三甲氧基异黄酮、卡霉素、亚油酸和咖啡酸，关键靶点为PTPN11、LCK、STAT3、GRB2、FYN、SRC、PIK3R1、LYN、EGFR、PIK3CA，关键通路为PI3K-Akt、脂质和动脉粥样硬化、JAK-STAT、FoxO和亚油酸代谢。转录组学分析显示，与模型组相比，QJSB下调1171个基因，上调382个基因。KEGG通路富集分析表明，PI3K-AKT信号通路与白细胞减少密切相关。动物实验表明，QJSB及其有效成分通过调节PI3K-AKT信号通路及下游转录因子mTOR和FOXO3A，有效提高模型大鼠血清造血及免疫相关细胞因子水平，改善胸腺指数、脾脏指数和骨髓有核细胞计数。结论本研究首次证实木黄酮、槲皮素和咖啡酸是黄芪皂苷的关键活性成分，黄芪皂苷可通过调控PI3K-AKT-mTOR/FoxO3a信号轴治疗白细胞减少症。

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Exploring the therapeutic mechanism of Miao nationality medicine Qijiao Shengbai capsule on leukopenia based on multi-omics, network pharmacology and experimental verification

Introduction

Leukopenia is caused by numerous factors, and modern drug therapies have obvious side effects, Qijiao Shengbai Capsule (QJSB) is a compound prescription developed from Miao medicine, widely used in clinical treatment of leukopenia. However, its mechanism of action for treating leukopenia remains unclear.

Objectives

This study aims to investigate the active ingredients, effects and underlying mechanism of QJSB on leukopenia.

Materials and methods

In this study, the chemical components of QJSB and serum constituents were identified using UPLC-Q-Qrbitrap HRMS technology. The potential anti-leukopenia mechanism and crucial components of QJSB was deciphered using combined approaches of transcriptomic analysis and network pharmacology analysis. Finally, the expression of key targets and the intervene effects of QJSB in the cyclophosphamide-induced leukopenia model of rats was verified by in vivo experiments.

Results

In total, 51 and 58 chemical components were identified from QJSB and serum respectively. The network pharmacology analysis indicated that the key components of QJSB was genistein, quercetin, 5,6,7-trimethoxyisoflavone, carbacyclin, linoleic acid, and caffeic acid, the key targets were PTPN11, LCK, STAT3, GRB2, FYN, SRC, PIK3R1, LYN, EGFR, PIK3CA, and the key pathways were PI3K-Akt, lipid and atherosclerosis, JAK-STAT, FoxO, and linoleic acid metabolism. Transcriptomics analysis revealed that 1171 genes were down-regulated and 382 genes were up-regulated by QJSB compared with model group. KEGG pathway enrichment analysis indicated that the PI3K-AKT signaling pathway is closely related to leukopenia. Animal experiments demonstrated that QJSB and its active components effectively increased serum levels of hematopoietic and immune-related cytokines, improved thymus index, spleen index, and bone marrow nucleated cell count in model rats through regulating PI3K-AKT signaling pathway and downstream transcription factors mTOR and FOXO3A.

Conclusion

Our research demonstrated for the first time that genistein, quercetin, and caffeic acid is the key active components of QJSB and this miao nationality medicine can treat leukopenia through regulating the PI3K-AKT-mTOR/FoxO3a signaling axis.

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.