Efficacy and Mechanism of Buxue Yimu Pillson Gynecological Anemia:A Combination of Clinical and Network Pharmacology Study

Objective:Tocompare the clinical efficacyand safety of oral administration of BuxueYimuPills(BYP),ferrous sulfate(FS),and the combination of BYP and FS on gynecological anemia,and investigate the mechanisms using network pharmacology.Methods:A randomized,controlled,multi-center clinical trial was conducted.Totally 150 patients with hemoglobin of 70-110 g/L due to gynecological conditions were recruited and randomized(using the block randomization method)into Buxue Yimu Pills group(24 g/d),oral iron group(FS Tablets,0.9 g/d),and combined treatment group(BYP,24g/d plus FS Tablets,0.9 g/d),50 patients in each group.At the enrollment and 4-week treatment,complete blood count,serum iron indexes were evaluated.Adverse events,liver and renal functions,as well as blood coagulation were observed.Network pharmacology was conducted to identify the active ingredients and explore the potential mechanisms of BYP.Results:Ten(20%)and 7(14%)participants discontinued the therapy due to gastrointestinal symptoms in oral iron and combination treatment groups.All 3 groups showed elevated hemoglobin.The patients in the iron group exhibited typically elevated in serum iron and ferritin and decreased in total iron-binding capacity.No change in iron indexes was observed in BYP group.The patients in the combination treatment group neither showed significant changes in serum ferritin nortotal iron-binding capacity.No significant adverse reactions were observed in the BYP group.The network pharmacology identified 27 bioactive compounds and 145 targets of BYP on gynecological anemia.Biological processes and pathways including regulation of inflammation,hormone,angiogenesis and hemostasis,responsetodecreased oxygen levels,effects on myeloma cell,and responseto metal ions were identified.Conclusion:BYP contributes to the practical improvement on gynecological anemia potentially through multi-target mechanisms and optimized iron re-distribution.

Exploring the mechanism of Buxue Yimu Pill on hemorrhagic anemia through molecular docking, network pharmacology and experimental validation

Buxue Yimu Pill(BYP) is a classic gynecological medicine in China, which is composed of Angelica sinensis(Oliv.)Diels, Leonurus japonicus Houtt, Astragalus membranaceus(Fisch.) Bunge, Colla corii asini and Citrus reticulata Blanco. It has been widely used in clinical therapy with the function of enriching Blood, nourishing Qi, and removing blood stasis. The current study was designed to determine the bioactive molecules and therapeutic mechanism of BYP against hemorrhagic anemia. Herein, GC-MS and UPLC/Q-TOF-MS/MS were employed to identify the chemical compounds from BYP. The genecards database(https://www.genecards.org/) was used to obtain the potential target proteins related to hemorrhagic anemia. Autodock/Vina was adopted to evaluate the binding ability of protein receptors and chemical ligands. Gene ontology and KEGG pathway enrichment analysis were conducted using the Cluster Profiler. As a result, a total of 62 candidate molecules were identified and 152 targets related to hemorrhagic anemia were obtained. Furthermore, 34 active molecules and 140 targets were obtained through the virtual screening experiment. The data of molecular-target(M-T), target-pathway(T-P), and molecular-target-pathway(M-T-P) network suggested that 32 active molecules enhanced hematopoiesis and activated the immune system by regulating 57 important targets. Pharmacological experiments showed that BYP significantly increased the counts of RBC, HGB, and HCT, and significantly down-regulated the expression of EPO, IL-6, CSF3,NOS2, VEGFA, PDGFRB, and TGFB1. The results also showed that leonurine, leonuriside B, leosibiricin, ononin, rutin, astragaloside I, riligustilide and levistolide A, were the active molecules closely related to enriching Blood. In conclusion, based on molecular docking, network pharmacology and validation experiment results, the enriching blood effect of BYP on hemorrhagic anemia may be associated with hematopoiesis, anti-inflammation, and immunity enhancement.