Global Metabolomic and Lipidomic Analysis Reveals the Potential Mechanisms of Hemolysis Effect of Ophiopogonin D and Ophiopogonin D' in vivo
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Xu Huan-Hua, Zhen-Hong Jiang, Cong-Shu Huang, Yu-Ting Sun, Long-Long Xu, Xiang-Ling Tang, Hong-Ling Tan, Zeng-Chun Ma, Yue Gao
2020
unpublished
Background: 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. The primary cause
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... of hemolysis in vitro has been confirmed to be related to the difference between physical and chemical properties of OPD and OPD', but the mechanism of hemolysis in vivo is still unclear, especially the existing research 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.Methods: 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.Results: 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.Conclusions: This study confirmed that interference of phospholipid metabolism was the main cause of hemolysis of OPD and OPD'. This study provided a comprehensive description of metabolome and lipidomic changes under the condition of hemolysis which caused by OPD and OPD'. It can also provide clues for research on the hemolysis mechanism of traditional Chinese medicine.
doi:10.21203/rs.3.rs-56883/v2
fatcat:uz26fromc5brjbjiz46glfdyhu