Xu Huan-Hua, Jiang Zhen-Hong, Huang Cong-Shu, Sun Yu-Ting, Xu Long-Long, Tang Xiang-Ling, Tan Hong-Ling, Ma Zeng-Chun, Gao Yue
Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, 100850, China.
Chin Med. 2021 Jan 6;16(1):3. doi: 10.1186/s13020-020-00412-z.
OPD and OPD' are the two main active components of Ophiopogon japonicas in Shenmai injection (SMI). Being isomers of each other, they are supposed to have similar pharmacological activities, but the actual situation is complicated. The difference of hemolytic behavior between OPD and OPD' in vivo and in vitro was discovered and reported by our group for the first time. In vitro, only OPD' showed hemolysis reaction, while in vivo, both OPD and OPD' caused hemolysis. In vitro, the primary cause of hemolysis has been confirmed to be related to the difference between physical and chemical properties of OPD and OPD'. In vivo, although there is a possible explanation for this phenomenon, the one is that OPD is bio-transformed into OPD' or its analogues in vivo, the other one is that both OPD and OPD' were metabolized into more activated forms for hemolysis. However, the mechanism of hemolysis in vivo is still unclear, especially the existing literature are still difficult to explain why OPD shows the inconsistent hemolysis behavior in vivo and in vitro. Therefore, the study of hemolysis of OPD and OPD' in vivo is of great practical significance in response to the increase of adverse events of SMI.
Aiming at the hemolysis in vivo, this manuscript adopted untargeted metabolomics and lipidomics technology to preliminarily explore the changes of plasma metabolites and lipids of OPD- and OPD'-treated rats. Metabolomics and lipidomics analyses were performed on ultra-high performance liquid chromatography (UPLC) system tandem with different mass spectrometers (MS) and different columns respectively. Multivariate statistical approaches such as principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) were applied to screen the differential metabolites and lipids.
Both OPD and OPD' groups experienced hemolysis, Changes in endogenous differential metabolites and differential lipids, enrichment of differential metabolic pathways, and correlation analysis of differential metabolites and lipids all indicated that the causes of hemolysis by OPD and OPD' were closely related to the interference of phospholipid metabolism.
This study provided a comprehensive description of metabolomics and lipidomics changes between OPD- and OPD'-treated rats, it would add to the knowledge base of the field, which also provided scientific guidance for the subsequent mechanism research. However, the underlying mechanism require further research.
麦冬多糖（OPD）和麦冬多糖'（OPD'）是参麦注射液（SMI）中麦冬的两个主要活性成分。它们互为异构体，理应具有相似的药理活性，但实际情况较为复杂。本课题组首次发现并报道了OPD和OPD'在体内外溶血行为的差异。体外实验中，只有OPD'表现出溶血反应，而在体内实验中，OPD和OPD'均引起溶血。体外实验中，溶血的主要原因已证实与OPD和OPD'的物理化学性质差异有关。在体内实验中，尽管对此现象有一些可能的解释，一种是OPD在体内生物转化为OPD'或其类似物，另一种是OPD和OPD'均代谢为更具活性的形式导致溶血。然而，体内溶血机制仍不清楚，尤其是现有文献仍难以解释为何OPD在体内和体外表现出不一致的溶血行为。因此，研究OPD和OPD'在体内的溶血情况对于应对SMI不良事件的增加具有重要的实际意义。
针对体内溶血情况，本研究采用非靶向代谢组学和脂质组学技术初步探究OPD和OPD'处理大鼠血浆代谢物和脂质的变化。代谢组学和脂质组学分析分别在配备不同质谱仪（MS）和不同色谱柱的超高效液相色谱（UPLC）系统上进行。应用主成分分析（PCA）和正交偏最小二乘法判别分析（OPLS-DA）等多元统计方法筛选差异代谢物和脂质。
OPD组和OPD'组均出现溶血现象，内源性差异代谢物和差异脂质的变化、差异代谢途径的富集以及差异代谢物和脂质的相关性分析均表明，OPD和OPD'引起溶血的原因与磷脂代谢的干扰密切相关。
本研究全面描述了OPD和OPD'处理大鼠之间的代谢组学和脂质组学变化，为该领域增加了知识库内容，也为后续机制研究提供了科学指导。然而，其潜在机制仍需进一步研究。
