Mechanism Study of Jiuwei Buxue Oral Liquid on Improving Hematopoietic Function in Blood Deficiency Mice Based on Anti-inflammation and Erythropoiesis Effects
This study aimed to investigate the effect and mechanism of Jiuwei Buxue Oral Liquid on improving hematopoietic function in blood deficiency mice.The chemical constituents in Jiuwei Buxue Oral Liquid were identified by Ultra-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry(UPLC-Q-TOF-MS/MS).The key network targets of Jiuwei Buxue Oral Liquid in the treatment of anemia were screened by protein interaction and network analysis,and the key network targets were analyzed by Gene Ontology(GO)analysis and KEGG pathway enrichment analysis.At the same time,molecular docking technology was used to dock potential active components with key network targets to evaluate the binding a-bility of active molecules to targets.In the animal experiment,the blood deficiency model of mice was estab-lished by cyclophosphamide,and the control group and model group,Fufang E Jiao Jiang Oral Liquid group(30 mL/kg)and Jiuwei Buxue Oral Liquid high,medium and low dose groups(10.0,5.0,2.5 mL/kg)were established.The mice were intra-gastrically administered once a day for 32 consecutive days.The levels of Red Blood Cell(RBC),Hemoglobin(HGB)and Hematocrit(HCT)in whole blood were detected,and the expression of key targets and pathways in the kidney of mice with blood deficiency syndrome was verified by qRT-PCR and Western blotting.The results showed that among the 91 identified chemical components of Ji-uwei Buxue Oral Liquid,a total of 15 potential active components that met the conditions of oral bioavailabili-ty(OB)≥30%and drug similarity(DL)≥0.18 and had corresponding targets were obtained.The compo-nent-blood deficiency disease target network of Jiuwei Buxue Oral Liquid was analyzed,and 15 key targets of Jiuwei Buxue Oral Liquid in the treatment of anemia were obtained,which were mainly enriched in Nuclear Factor-κB(NF-κB)signaling pathway,Metabolic pathway,Hypoxia-inducible factor-1(HIF-1)signaling pathway,Toll-like receptor signaling pathway and other pathways.Molecular docking results showed that Liquiritin and Hesperetin had strong binding ability with Toll-like receptor 4(TLR4).The results of animal experiments showed that compared with the control group,the levels of RBC,HGB and HCT in blood defi-ciency mice were significantly decreased,and the inflammatory signal mediated by TLR4/NF-κB p65 was en-hanced.And the signal of Hypoxia-inducible factor-1α(HIF-1α)/Erythropoietin(EPO)mediated erythropoi-esis was inhibited(P＜0.05 or P＜0.01).Compared with model group,the levels of RBC,HGB and HCT in mice with blood deficiency syndrome were significantly increased in each dose group of Jiuwei Buxue Oral Liquid.The changes of TLR4 and NF-κB p65 were reversed to varying degrees,and the expression levels of HIF-1α and EPO mRNA or protein were up-regulated(P＜0.05 or P＜0.01).Therefore,Jiuwei Buxue Oral Liquid can improve the anemia status of mice with blood deficiency syndrome,and its mechanism may be re-lated to the promotion of HIF-1α/EPO-mediated erythropoiesis in the kidney and the reduction of TLR4/NF-κB p65-mediated renal inflammatory response.
Jiuwei Buxue Oral Liquidsyndrome of blood deficiencynetwork pharmacologyinflammationerythropoiesisHypoxia-inducible factor-1(HIF-1)
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