| Objective:(1)To establish the traceability analysis method of Sanguisorba officinalis L.from different regions and find out the different components;(2)To reveal the changes of metabolic profile and the potential pathogenesis of diseases in mice with radiation-induced thrombocytopenia;(3)To study the therapeutic effect and potential mechanism of Sanguisorba officinalis L.on mice with radiation-induced thrombocytopenia.Methods:(1)Non-targeted metabolomics method based on mass spectrometry was used to conduct PCA and PLS-DA analysis of Sanguisorba officinalis L.from different regions to reveal the different components;(2)PCA and OPLS-DA were performed on serum of mice in normal and irradiated mice to reveal the changes of endogenous metabolites and related pathways after radiation,and to explore the pathological mechanism of radiationinduced thrombocytopenia.(3)The platelet counts of mice in normal group,model group,positive drug group,and Sanguisorba officinalis L.group were measured at different time points in mice.The organs were stripped to measure the organ index and serums were collected to detect the biochemical indexes,so as to evaluate the platelet recovery effect of Sanguisorba officinalis L.and its toxicity on irradiated mice.(4)Serum metabolomics was used to analyze the endogenous metabolic profiles of mice in normal group,model group and Sanguisorba officinalis L.group by PCA and PLS-DA.The regulatory effects of Sanguisorba officinalis L.on abnormal metabolites and the related pathways in irradiated mice were revealed,and the relevant mechanisms were discussed.Result:(1)An analytical method was successfully established to distinguish geographical origin of Sanguisorba officinalis L.,and 30 different components were identified among samples from Gansu,Shandong and Anhui,and 10 compounds were selected as characteristic markers to distinguish Sanguisorba officinalis L.from different regions;(2)Irradiation could significantly reduce the number of platelets in mice,and 56 metabolites up-regulated and 10 metabolites down-regulated by radiation.These metabolites are related to glycerophospholipid metabolism,nicotinate and nicotinamide metabolism,sphingolipid metabolism,nositol phosphate metabolism,and tryptophan metabolism.Further verification showed that Ltryptophan,Lyso PC(17:0)and D-sphinganine induced apoptosis of K562 cells,and L-tryptophan inhibited differentiation of K562 cells.Platelet counts returned to normal after 30 days of radiation exposure,as did levels of L-tryptophan,Lyso PC(17:0)and D-sphinganine.L-tryptophan,Lyso PC(17:0)and Dsphinganine may be potential biomarkers for radiation-induced thrombocytopenia.(3)Sanguisorba officinalis L.could promote the platelet recovery of irradiated mice,has no effect on the body weight of mice,has no toxicity to organs,and could reduce the serum ALT and LDH levels of irradiated mice.(4)Sanguisorba officinalis L.can increase platelet count in irradiated mice by inhibiting apoptosis of Bone marrow(BM)cells and promoting megakaryocyte differentiation.The mechanism of action of Sanguisorba officinalis L.against thrombocytopenia may be that the administration of Sanguisorba officinalis L.resulted in the modulation of 46 abnormal metabolites,leding to the regulation of associated pathways such as glycerophospholipid metabolism,nicotinate and nicotinamide metabolism,sphingolipid metabolism,and tryptophan metabolism,which was beneficial for the recovery of platelet levels.Niacinamide and Lyso PC(17:0)may be potential biomarkers for the treatment of radiation-induced thrombocytopenia by Sanguisorba officinalis L.Conclusion:(1)The established method of distinguish geographical origin can accurately characterize the chemical composition differences of Sanguisorba officinalis L.from different regions.The method can be used for origin quality control of Sanguisorba officinalis L.(2)After exposure to radiation,the platelet count in mice was significantly reduced,potentially due to alterations in levels of various endogenous metabolites such as L-tryptophan,Lyso PC(17:0),and D-sphinganine.These metabolites reduced the platelet counts by inhibiting megakaryocyte differentiation and inducing megakaryocyte apoptosis.(3)Sanguisorba officinalis L.could promote platelet production in irradiated mice by regulating Lyso PC(17:0),niacinamide and other endogenous metabolites and their related metabolic pathways. |
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