Qijiao Shengbai Capsule alleviated leukopenia by interfering leukotriene pathway: Integrated network study of multi-omics.

BACKGROUND: Leukopenia could be induced by chemotherapy, which leads to bone marrow suppression and even affects the therapeutic progression of cancer. Qijiao Shengbai Capsule (QSC) has been used for the treatment of leukopenia in clinic, but its bioactive components and mechanisms have not yet been elucidated clearly. PURPOSE: This study aimed to elucidate the molecular mechanisms of QSC in treating leukopenia. STUDY DESIGN: Serum pharmacochemistry, multi-omics, network pharmacology, and validation experiment were combined to study the effect of QSC in murine leukopenia model. METHODS: First, UPLC-QTOF-MS was used to clarify the absorbed components of QSC. Then, cyclophosphamide (CTX) was used to induce mice model with leukopenia, and the therapeutic efficacy of QSC was assessed by an integrative approach of multi-omics and network pharmacology strategy. Finally, molecular mechanisms and potential therapeutic targets were identified by validated experiments. RESULTS: 121 compounds absorbed in vivo were identified. QSC significantly increase the count of white blood cells (WBCs) in peripheral blood of leukopenia mice with 15 days treatment. Multi-omics and network pharmacology revealed that leukotriene pathway and MAPK signaling pathway played crucial roles during the treatment of leukopenia with QSC. Six targets (ALOX5, LTB4R, CYSLTR1, FOS, JUN, IL-1ß) and 13 prototype compounds were supposed to be the key targets and potential active components, respectively. The validation experiment further confirmed that QSC could effectively inhibit the inflammatory response induced by leukopenia. The inhibitors of ALOX5 activity can significantly increase the number of WBCs in leukopenia mice. Molecular docking of ALOX5 suggested that calycosin, daidzein, and medicarpin were the potentially active compounds of QSC. CONCLUSION: Leukotriene pathway was found for the first time to be a key role in the development of leukopenia, and ALOX5 was conformed as the potential target. QSC may inhibit the inflammatory response and interfere the leukotriene pathway, it is able to improve hematopoiesis and achieve therapeutic effects in the mice with leukopenia.

[Reversal effect of hyperthemia on multidrug resistant phenomena].

OBJECTIVE: The purpose of this study was investigate the effect of hyperthemia on multidrug resistance in K562/ADM cell. METHODS: The MDR1 (mulitdrug resistance gene) and MRP (multidrug resistant associated gene) gene expressions in Tca8113 and K562/ADM cell lines were analyzed by RT-PCR after treated with different cytotoxic drugs and different temperature (37 degrees C and 41 degrees C). The function and expression of Pgp and MRP were detected by fluorescence photometeric assays. RESULTS: Inhibition rate of both cells was significantly enhanced by exposure to chemotherapeutic drugs and 41 degrees C temperature; Exposing to 41 degrees C hyperthemia reduced MDR1 and MRP expression and enhanced intracellular drug concentration as well in K562/ADM. CONCLUSION: 41 degrees C hyperthemia could effectively enhance the inhibition rate of chemotherapeutic drugs and partially reverse the multidrug resistance. It is suggested that hyperthemia could be used as a method to overcome multidrug resistance.