探索刺柏胶囊治疗白细胞减少症的潜在生物活性化合物组及作用机制：网络药理学与转录组证据相结合的方法

Exploring the potential bioactive compounds group and mechanism of Ci Bai Capsule in treating leukopenia: a combined approach of network pharmacology and transcriptome evidences.

作者信息

Zhang Dingfan, Huang Congshu, Zhou Lei, Wang Boyang, Zhou Wei, Xia Tiantian, Shen Pan, Li Shao, Gao Yue

机构信息

Institute for TCM-X, MOE Key Laboratory of Bioinformatics/Bioinformatics Division, BNRIST, Department of Automation, Tsinghua University, Beijing, 100084, China.

College of Traditional Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, 455046, China.

出版信息

Chin Med. 2025 Sep 1;20(1):139. doi: 10.1186/s13020-025-01197-9.

DOI:10.1186/s13020-025-01197-9

PMID:40890790

Abstract

BACKGROUND

Radiation-induced leukopenia caused by low-dose exposure is frequently associated with Traditional Chinese Medicine (TCM) syndromes like "blood deficiency" and "fatigue syndrome". Ci Bai Capsule (CB) has been reported to enhance white blood cell levels; however, its mechanisms and bioactive compounds remain unclear.

AIM

This study aimed to identify the bioactive compounds group of CB and elucidate its potential mechanisms in radiation-induced leukopenia.

METHODS

Syndrome-related data were gathered from SYMMAP and CTD database. CB's target profile is predicted by DrugCIPHER. Network pharmacology approaches were employed to identify active compounds and related pathways. Experimental validation was conducted through flow cytometry, RNA-sequencing both ex vivo and in vivo models. RT-qPCR and Western blot were performed for quantitative validation of key targets.

RESULTS

A total of 22 pathways related to cellular processes, immune responses, and signal transduction were identified. Five key bioactive compounds (kaempferol-3-glucorhamnoside, syringin, schisandrin, 3-hydroxytyrosol 3-O-glucoside and salidroside) were found to significantly modulate syndrome-related pathways. Optimal dosing of this compound combination enhanced leukocyte counts and splenic immune cell proliferation in irradiated mice. Transcriptomic analysis revealed that the compounds exert regulatory effects on PP1A, RB, CDK4/6, CDK2, and CDK1, thereby modulating downstream immune and hematopoietic markers such as MNDA, BST2, and HSPA1A.

CONCLUSION

Our findings suggest that CB mitigates radiation-induced leukopenia by enhancing immune and hematopoietic recovery, offering a promising therapeutic approach for managing radiation-related hematological disorders.

摘要

背景

低剂量暴露引起的辐射诱导白细胞减少症常与“血虚”和“疲劳综合征”等中医证候相关。据报道，刺柏胶囊（CB）可提高白细胞水平；然而，其作用机制和生物活性成分仍不清楚。

目的

本研究旨在确定CB的生物活性成分组，并阐明其在辐射诱导白细胞减少症中的潜在机制。

方法

从SYMMAP和CTD数据库收集证候相关数据。通过DrugCIPHER预测CB的靶点谱。采用网络药理学方法确定活性成分和相关通路。通过流式细胞术、体外和体内模型的RNA测序进行实验验证。采用RT-qPCR和蛋白质免疫印迹法对关键靶点进行定量验证。

结果

共鉴定出22条与细胞过程、免疫反应和信号转导相关的通路。发现5种关键生物活性成分（山奈酚-3-葡萄糖鼠李糖苷、紫丁香苷、五味子醇甲、3-羟基酪醇3-O-葡萄糖苷和红景天苷）可显著调节证候相关通路。该化合物组合的最佳剂量可提高受辐照小鼠的白细胞计数和脾免疫细胞增殖。转录组分析表明，这些化合物对PP1A、RB、CDK4/6、CDK2和CDK1具有调节作用，从而调节下游免疫和造血标志物，如MNDA、BST2和HSPA1A。