| Rationales:Astragalus(AR)is a perennial herbal and leguminous plant,mainly distributed in North and Northwest China,including Astraglalus mevyibranaceos(Fisch.)Bge.var.and mongholicus(Bge.)Hsiao.It is a famous multi-effect Traditional Chinese Medicine(TCM),which can play various effects in different compatibility environments of TCM compound prescription,such as invigorating Qi,strengthening the heart,reducing blood pressure and antibacterial.Wild-simulated Astragali Radix(WAR)demand exceeds supply which due to it has the long growth period.There is a transplanted Astragali Radix(TAR)with a growth period shortened,and its chemical composition is similar to that of WAR,but the clinical efficacy of TAR is worth studying.Danggui Buxue Decoction(DBD),which is composed of Astragalus and Angelica sinensis according to a ratio of 5:1,is widely used in clinical treatment of blood deficiency because of its classic compatibility and blood-enhancing effects.Moreover,DBD,as a formula for nourishing blood,whose mechanism and compatibility classics for treating blood deficiency still deserves in-depth study.Therefore,in this study,DBD was used as the carrier for evaluating the efficacy,and acetylphenazine(APH)and cyclophosphamide(CTX)compound blood deficiency mouse model was used as the disease environment.Using traditional medicinal efficacy indicators and metabolomics to explore the effect and mechanism of DBD with different AR compatibility on improving blood deficiency,and the compatibility mechanism of DBD was interpreted by the metabolomics.At the same time,with the help of network pharmacology,the mechanism of DBD was further explored.Objective:Comparing the blood-purifying efficacy of WAR and TAR,clarifying the blood-supplementing and compatibility mechanism of Danggui Buxue Decoction,providing scientific basis for quality control of Astragalus membranaceus for different effects,and providing scientific and effective basis for clinical application of Danggui Buxue Decoction.Methods:(1)Establishing a compound blood deficiency mouse model with acephenazine and cyclophosphamide,screening the optimal dose of Danggui Buxue Decoction with traditional medicinal efficacy indicators,determing the efficacy and mechanism of Danggui Buxue Decoction in the treatment of blood deficiency by the spleen metabonomics and lipidomics techniques.(2)Establishing a compound blood deficiency mouse model with acephenazine and cyclophosphamide,and the efficacy of Danggui Buxue Decoction compatibility of WAR and TAR was compared by using the serum metabolomics technology.(3)Establishing a compound blood deficiency mouse model with acephenazine and cyclophosphamide,the compatibility Danggui Buxue Decoction was studied by using the serum metabolomics technology.(4)By using the TCM inheritance support system,we cleared the core compatibility of Astragali Radix-Angelica Sinensis.Batman-TCM?GeneCards,OMIM were used to predict and screen the targets of "Astragali Radix-Angelica Sinensis".Cytoscape software was used to construct the medicinal material-component-target network,and the topological attribute analysis and cluster analysis of the target were performed by its Network Analyzer,ClusterViz and other tools.The GO and KEGG pathways involved in the targets were analyzed by DAVID,PharmGkb,CTD and MESH were used to classify diseases according to potential targets.Results:(1)Compared with the normal group,the mice in the model group showed abnormal mental status,mental atrophy,and slow action;significant weight loss;splenomegaly and thymus atrophy;all hematological indicators were significantly reduced;cystic expansion in the bone marrow cavity,fat There are more cells,lower bone marrow cell proliferation,and fewer hematopoietic cells.This shows that the mouse model of blood deficiency with compound acephenazine and cyclophosphamide was successfully established.After administering Fufang E,jiao Jiang and Danggui Buxue Decoction in low,medium and high-dose groups,the optimal dose of Danggui Buxue Decoction improving the APH and CTX composite blood deficiency model was the high-dose group(18 g/kg),which was selected by comprehensiving evaluation of the appearance of mental state,xveight,organ index,hematology routine,and femoral pathological sections.Spleen metabolomics and lipidomics found that 8 polar differential metabolites and 18 non-polar differential lipid metabolites were closely related to blood deficiency.Pathway analysis further showed that disorders of pyrimidine metabolism and glycerophospholipid metabolism were disrupted in APH and CTX model.After giving Danggui Buxue Decoction,cytosine,uracil,and phosphatidylcholine(o-16:1(9Z)/20:0,20:4/20:4,38:6),ete,7 and 10 differential metabolites were returned to normal levels,and improved the APH and CTX blood deficiency caused by regulating pyrimidine metabolism and glycerophospholipid metabolism.Compared with previous related studies,the differential metabolites identified in this experiment are more comprehensive,and it was found that Danggui Buxue Decoction can recall many lipid metabolites and improve blood deficiency by regulating lipid metabolism such as glycerophospholipid metabolism.(2)The mice of blood deficiency were given Danggui Buxue Decoction of compatibiling WAR and TAR with angelica respectively.It was found that Danggui Buxue Decoction with WAR was stronger than Danggui Buxue Decoction with TAR.The serum metabolomics found that 17 serum differential metabolites,and through pathway analysis,it was found that the combined modeling of APH and CTX would affect the biosynthesis of phenylalanine,tyrosine,and tryptophan,causing arachidene disorders of acid metabolism and tyrosine metabolism.After giving Danggui Buxue Decoction compatible with WAR and TAR respectively,it can be found that Danggui Buxue Decoction with WAR can significantly revert 13 serum differential metabolites with a callback rate of 76%;The other decoction of TAR can only call back 8 serum differential metabolites with a callback rate of 47%.Comparing the callback levels of the 8 different metabolites that were both corrected,it was found that the callback effect of Danggui Buxue Decoction with WAR was higher than TAR.(3)After blood deficiency mice were administered with Astragalus,Angelica group and Danggui Buxue Decoction,it was found that the Danggui Buxue Decoction group(WAR)of the improvement effect on blood deficiency is obviously better than the single-drug astragalus and angelica by comprehensive analysing of appearance and mental state,body weight,organ index,hematology routine,and various medicinal efficacy indicators of femoral pathological sections.Danggui Buxue Decoction compatible with WAR can significantly recall 13 serum differential metabolites with a callback rate of 76%;while the single-drug Angelica sinensis can only recall 6 differential metabolites with a callback rate of 35%.The single-drug Astragalus membranaceus could significantly revert 4 differential metabolites,xvith a reversion rate of 23%.(4)Totally 459 prescriptions were included in this study,involving 641 Chinese herbs.With a support degree of 25%in analysis,33 most eommonly used drug combinations were screened,which were mainly used to treat 9 types of diseases.Astragali Radix was often used to treat consumptive disease,and the core combination "Astragali Radix-Angelica Sinensis" was also often used to treat,consistent with ancient record and clinical medication.The results showed that 105 active components and 127 targets of "Astragali Radix-Angelica Sinensis" were involved.The network results showed that the process of Immune response,oxidative stress,signal transduction were mainly involved,which played a role in the treatment of consumptive disease,by adjusting the Pathways in cancer?Cytokine-cytokine receptor interaction?Proteoglycans in cancer?PI3K-Akt?MAPK signaling pathway and other signal pathways to play its treating consumptive disease effect.Conclusion:Combined the traditional pharmacodynamic indicators?metabonomics and network pharmacology methods,based on the compatibility of Danggui Buxue Decoction in treating blood deficiency mice,the topic compares the efficacy and mechanism of WAR and TAR.The blood-improving effect of WAR is stronger,more differential metabolites related to blood deficiency are identified,and the blood-improving mechanism research of Danggui Buxue Decoction is more eomprehensive.At the same time,the compatibility mechanism of Danggui Buxue Decoction was elucidated from the perspective of metabolomics and network pharmacology. |
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