4.6 Article

Systems biology analysis of the effect and mechanism of total flavonoids of Astragali Radix against cyclophosphamide-induced leucopenia in mice

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ELSEVIER
DOI: 10.1016/j.jpba.2021.114357

关键词

Total flavonoids of Astragali Radix; LC-MS metabolomics; Network pharmacology; Leucopenia

资金

  1. National Key Research and Development Program of China [2019YFC1710800]
  2. Shanxi Scholarship Council of China [2017-017]

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Total flavonoids extracted from Astragali Radix exhibit protective effects against leucopenia possibly by modulating immunologic functions, promoting cell proliferation, and regulating related metabolic pathways at the system level.
This study aimed to demonstrate the pharmacological mechanism of total flavonoids extracted from Astragali Radix (AR) on cyclophosphamide (Cy)-induced leucopenia in mice. First, flow cytometry, network pharmacology and plasma metabolomics were integrated to investigate the pharmacological mechanism of total flavonoids, the targets from network pharmacology and metabolites from metabolomics were analyzed by DAVID. Then, the key cytokines were validated to confirm the predicted metabolic pathway results. The results showed that total flavonoids significantly increased body weight, routine blood indices, bone marrow DNA cells, and also markedly caused lymphocyte proliferation by increasing the percentages of CD4(+) and CD8(+). Using network pharmacology and metabolomics methods, the study identified 13 signal-related pathways regulated by total flavonoids including PI3K-Akt signaling pathway, Jak-STAT signaling pathway, Sphingolipid signaling pathway, and so on. Total flavonoids also reversed changes in serum cytokines IL-2, IL-6, and GM-CSF. Total flavonoids exhibits protective effects against leucopenia probably by modulating immunologic functions, promoting cell proliferation, and regulating related metabolic pathways at the system level. (C) 2021 Published by Elsevier B.V.

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