Zhang Shiyu, Mi Yinxiao, Ye Tingting, Lu Xiaoyan, Liu Li, Qian Jing, Fan Xiaohui
Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Chiatai Qingchunbao Pharmaceutical Co. Ltd, Hangzhou, 310030, China.
Chin Med. 2022 Nov 4;17(1):124. doi: 10.1186/s13020-022-00678-5.
Shenmai injection (SMI), a traditional Chinese medicine (TCM) injection prepared from Red ginseng and Ophiopogon japonicus, is widely used in clinics to treat chemotherapy-induced myelosuppression. Similar to other TCM injections, SMI contains a high amount of carbohydrates (fructose, sucrose, and maltose) in addition to the bioactive substances, specifically ginsenosides (Rg1, Re, and Rb1). To date, the role of these carbohydrates in the hematopoietic function of SMI remains unclear.
We aimed to investigate the hematopoietic effects and potential mechanisms of SMI and its components, focusing on the carbohydrates present in SMI.
EXPERIMENTAL DESIGN/METHODS: First, we evaluated the hematopoietic effect of SMI on 5-fluorouracil (5-FU)-induced myelotoxicity in a tumor-bearing mouse model. Then we prepared mixtures of ginsenosides and carbohydrates according to their proportions in SMI and evaluated their hematopoietic function in mice with 5-FU-induced myelosuppression. Finally, hematopoiesis-related molecular networks were built based on RNA sequencing (RNA-seq) of the bone marrow stromal cells (BMSCs), and the potential mechanisms of carbohydrates and ginsenosides were evaluated.
SMI attenuated 5-FU-induced myelotoxicity in tumor-bearing mice. Both ginsenosides and carbohydrates increased the bone marrow nucleated cell (BMNC) count and improved the bone marrow morphology in myelosuppressive mice; they promoted the proliferation of BMSCs derived from those myelosuppressive mice. Bioinformatics analyses revealed ECM-receptor interaction, Hippo signaling, and Wnt signaling are common pathways regulated by both ginsenosides and carbohydrates; Gstt1, Gstp2, Gsta4 and Oplah in Glutathione metabolism pathway and Cd19, Cd79a, and Cd79b in B cell receptor pathway are uniquely regulated genes related to carbohydrates but not ginsenosides.
Carbohydrates may collaborate with ginsenosides and contribute to the hematopoietic function of SMI. Carbohydrates could be considered as a bioactive component in this TCM injection.
参麦注射液（SMI）是一种由红参和麦冬制备的中药注射液，在临床上广泛用于治疗化疗引起的骨髓抑制。与其他中药注射液类似，SMI除了含有生物活性物质，特别是人参皂苷（Rg1、Re和Rb1）外，还含有大量碳水化合物（果糖、蔗糖和麦芽糖）。迄今为止，这些碳水化合物在SMI造血功能中的作用仍不清楚。
我们旨在研究SMI及其成分的造血作用和潜在机制，重点关注SMI中存在的碳水化合物。
实验设计/方法：首先，我们在荷瘤小鼠模型中评估了SMI对5-氟尿嘧啶（5-FU）诱导的骨髓毒性的造血作用。然后，我们根据人参皂苷和碳水化合物在SMI中的比例制备了混合物，并评估了它们对5-FU诱导的骨髓抑制小鼠的造血功能。最后，基于骨髓基质细胞（BMSC）的RNA测序（RNA-seq）构建造血相关分子网络，并评估碳水化合物和人参皂苷的潜在机制。
SMI减轻了荷瘤小鼠5-FU诱导的骨髓毒性。人参皂苷和碳水化合物均增加了骨髓抑制小鼠的骨髓有核细胞（BMNC）计数，并改善了骨髓形态；它们促进了源自这些骨髓抑制小鼠的BMSC的增殖。生物信息学分析表明，细胞外基质-受体相互作用、Hippo信号通路和Wnt信号通路是人参皂苷和碳水化合物共同调节的常见通路；谷胱甘肽代谢途径中的Gstt1、Gstp2、Gsta4和Oplah以及B细胞受体途径中的Cd19、Cd79a和Cd79b是与碳水化合物而非人参皂苷独特调节的基因。
碳水化合物可能与人参皂苷协同作用，有助于SMI的造血功能。碳水化合物可被视为这种中药注射液中的生物活性成分。
