Wu Shiyu, Wu Ruijun, Ma Siyi, Zhu Yiqing, Zhao Jing, Zhang Min, Huang Qian, Zeng Huawu, Ma Chi, Zhang Weidong, Ye Ji
School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China.
School of Pharmacy, Naval Medical University, Shanghai, 200433, China; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
J Ethnopharmacol. 2025 Aug 11;353(Pt A):120351. doi: 10.1016/j.jep.2025.120351.
Epimedium brevicornu Maxim., when used alone or as the principal component in traditional Chinese medicine (TCM) formulas, has the function of restoring internal "organs" and relieving fatigue. Shengbai Oral Liquid (SBOL), a TCM formula primarily composed of Epimedium brevicornu Maxim., has demonstrated clinical efficacy in managing chemotherapy- or radiotherapy-induced leukocytopenia. Nevertheless, its therapeutic mechanisms remain unclear.
Elucidate the mechanism of SBOL in treating chemotherapy-induced leukopenia.
A leukopenia model in mice was established using cyclophosphamide (CTX). Transcriptomic, proteomic, and metabolomic studies were performed to investigate mechanistic effects of SBOL at the genetic, protein, and metabolic levels. A comprehensive approach integrating multi-omics and network pharmacology was then employed to predict potential targets and pathways underlying the effects of SBOL. Finally, experiments were performed to validate the underlying molecular mechanisms and identify potential therapeutic targets.
SBOL (oral treatment for 18 days) significantly increased the white blood cell (WBC) count in the peripheral blood of mice with leukopenia. Additionally, SBOL can significantly increase the quantity and proliferative activity of bone marrow cells (BMCs). Further flow cytometry analysis showed that SBOL can increase the number of hematopoietic stem and progenitor cells (HSPCs) in BMCs. Specifically, it increased the populations of hematopoietic stem cells (HSCs), hematopoietic progenitor cells (HPCs), short term hematopoietic stem cells (ST-HSCs), and multipotent progenitor cells (MPPs) within the HSPCs. What is more, SBOL can also reduce spleen index and reverse the compensatory increase of HSPCs in the spleen. Transcriptomic analysis indicated SBOL is involved in lipid metabolism and immune regulation, while proteomic analysis identified pathways related to leukocyte migration and chemotaxis. Metabolomic analysis highlighted arachidonic acid and amino acid metabolism. Multi-omics and network pharmacology studies have suggested that Pro-Platelet Basic Protein (PPBP), ALOXE3, and CCR1 are key targets. Experiments confirmed that SBOL significantly elevated levels of hematopoietic factors, including CXCL12, TGF-β1, IL-34, IL-5, and GM-CSF. Additionally, SBOL reversed the decreased expression of PPBP in BMCs and restored serum PPBP levels in these mice with leukopenia.
SBOL significantly alleviates leukopenia induced by chemotherapy. It increases the bone marrow HSPCs counts and elevates serum hematopoietic factors levels in chemotherapy-treated mice, thereby restoring hematopoietic function and boosting WBCs counts. PPBP is closely related to the treatment of chemotherapy induced leukopenia by SBOL.
淫羊藿单独使用或作为中药配方中的主要成分时，具有补益脏腑、缓解疲劳的作用。升白口服液（SBOL）是一种主要由淫羊藿组成的中药配方，已在治疗化疗或放疗引起的白细胞减少症方面显示出临床疗效。然而，其治疗机制仍不清楚。
阐明SBOL治疗化疗引起的白细胞减少症的机制。
使用环磷酰胺（CTX）建立小鼠白细胞减少模型。进行转录组学、蛋白质组学和代谢组学研究，以研究SBOL在基因、蛋白质和代谢水平上的作用机制。然后采用多组学和网络药理学相结合的综合方法，预测SBOL作用的潜在靶点和途径。最后，进行实验以验证潜在的分子机制并确定潜在的治疗靶点。
SBOL（口服给药18天）显著增加了白细胞减少症小鼠外周血中的白细胞（WBC）计数。此外，SBOL可显著增加骨髓细胞（BMC）的数量和增殖活性。进一步的流式细胞术分析表明，SBOL可增加BMC中造血干细胞和祖细胞（HSPC）的数量。具体而言，它增加了HSPC中造血干细胞（HSC）、造血祖细胞（HPC）、短期造血干细胞（ST-HSC）和多能祖细胞（MPP）的数量。此外，SBOL还可降低脾脏指数，并逆转脾脏中HSPC的代偿性增加。转录组学分析表明SBOL参与脂质代谢和免疫调节，而蛋白质组学分析确定了与白细胞迁移和趋化性相关的途径。代谢组学分析突出了花生四烯酸和氨基酸代谢。多组学和网络药理学研究表明，前血小板碱性蛋白（PPBP）、ALOXE3和CCR1是关键靶点。实验证实，SBOL显著提高了造血因子的水平，包括CXCL12、TGF-β1、IL-34、IL-5和GM-CSF。此外，SBOL逆转了BMC中PPBP表达的降低，并恢复了这些白细胞减少症小鼠的血清PPBP水平。
SBOL显著减轻化疗引起的白细胞减少症。它增加了化疗治疗小鼠的骨髓HSPC计数，并提高了血清造血因子水平，从而恢复造血功能并提高WBC计数。PPBP与SBOL治疗化疗引起的白细胞减少症密切相关。
