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Integrated transcriptomic and metabolomic profiles reveal the protective mechanism of modified Danggui Buxue decoction on radiation-induced leukopenia in mice

Affiliation
School of Pharmacy ,Naval Medical University ,Shanghai ,China
Chen, Wei;
Affiliation
School of Pharmacy ,Shandong University of Traditional Chinese Medicine ,Jinan ,China
Xin, Jiayun;
Affiliation
School of Pharmacy ,Shandong University of Traditional Chinese Medicine ,Jinan ,China
Wei, Xintong;
Affiliation
School of Pharmacy ,Anhui University of Chinese Medicine ,Hefei ,China
Ding, Qianqian;
Affiliation
School of Pharmacy ,Naval Medical University ,Shanghai ,China
Shen, Yunheng;
Affiliation
School of Pharmacy ,Naval Medical University ,Shanghai ,China
Xu, Xike;
Affiliation
School of Pharmacy ,Shandong University of Traditional Chinese Medicine ,Jinan ,China
Wei, Yanping;
Affiliation
School of Pharmacy ,Shandong University of Traditional Chinese Medicine ,Jinan ,China
Lv, Yanhui;
Affiliation
School of Pharmacy ,Shandong University of Traditional Chinese Medicine ,Jinan ,China
Wang, Jie;
Affiliation
School of Pharmacy ,Guangdong Pharmaceutical University ,Guangzhou ,China
Li, Zhanhong;
Affiliation
School of Pharmacy ,Naval Medical University ,Shanghai ,China
Zhang, Weidong;
Affiliation
School of Pharmacy ,Naval Medical University ,Shanghai ,China
Zu, Xianpeng

Leukopenia caused by radiation hinders the continuous treatment of cancers. Danggui Buxue Decoction (DBD) has been widely used in clinical owing to low toxicity and definite therapeutic effects to increase leukocytes. Meanwhile, icaritin (ICT) has also been proved to have the effect of boosting peripheral blood cells proliferation. However, there is no study to prove the efficacy of MDBD (Modified Danggui Buxue Decoction), a derivative herbal formula composed of DBD and ICT, in the treatment of radiation-induced leukopenia. In this study, we performed a model of 3.5 Gy whole-body radiation to induce leukopenia in mice. The results of pharmacodynamic studies demonstrated that MDBD could significantly increase the white blood cells in peripheral blood by improving the activity of bone marrow nuclear cells, reducing bone marrow damage, modulating spleen index, and regulating hematopoietic factors to alleviate leukopenia. We also analyzed the integrated results of metabolomics and transcriptomics and found that MDBD could relieve leukopenia and alleviate bone marrow damage by targeting steroid biosynthesis and IL-17 signaling pathway, in which the key genes are Jun, Cxcl2 and Egr1. Therefore, our study provides a basis for the effectiveness and compatibility in the combination of traditional Chinese medicine formula and small molecule drugs.

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License Holder: Copyright © 2023 Chen, Xin, Wei, Ding, Shen, Xu, Wei, Lv, Wang, Li, Zhang and Zu.

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