Efficacy and Mechanism of Buxue Yimu Pills on Gynecological Anemia: A Combination of Clinical and Network Pharmacology Study.

Objective: To compare the clinical efficacy and safety of oral administration of Buxue Yimu Pills (BYP, 补血益母丸), 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, 24 g/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 nor total 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, response to decreased oxygen levels, effects on myeloma cell, and response to metal ions were identified. Conclusion: BYP contributes to the practical improvement on gynecological anemia potentially through multi-target mechanisms and optimized iron re-distribution. (Trial registration: No. NCT03232554) [ABSTRACT FROM AUTHOR]