PMID- 30978457 OWN - NLM STAT- MEDLINE DCOM- 20191220 LR - 20191220 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 238 DP - 2019 Jun 28 TI - Pharmacological and transcriptome profiling analyses of Fufang E'jiao Jiang during chemotherapy-induced myelosuppression in mice. PG - 111869 LID - S0378-8741(19)30616-6 [pii] LID - 10.1016/j.jep.2019.111869 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Fufang E'jiao Jiang (FEJ), a famous traditional Chinese medicine formula from "Liangyi Ointment", consists of five crude drugs, Colla corii asini, Radix Ginseng Rubra, Radix Rehmanniae Preparata, Codonopsis pilosula, and Crataegus pinnatifida Bge. It has pronounced functions of qi-nourishing and blood-activating. Recently, it has been widely used in China as a medication against myelosuppression in cancer treatment. AIM OF THE STUDY: We aimed to investigate the complex mode of action and underlying mechanisms of Fufang E'jiao Jiang (FEJ) regarding its hematopoietic effect. MAIN METHODS: Mice were divided into 5 groups of control, model, high dose FEJ (HFEJ), medium dose FEJ (MFEJ) and low dose FEJ (LFEJ). After 10 days from the administration, bone marrow cells (BMCs) were extracted for nucleated cells counts, flow cytometry analysis of hematopoietic stem cells (HSCs) population, as well as hematopoietic progenitor cells (HPCs) colony-forming unit (CFU) assay. A portion of bone marrow nucleated cells (BMNCs) of MFEJ group were prepared for RNA sequencing (RNA-Seq). The transcriptome data were analyzed based on the differentially expressed genes (DEGs). The molecular mechanisms of FEJ were deducted based on the biological processes and protein-protein interaction (PPI) network. RESULTS: FEJ could significantly increase the percentage of HSCs and the quantities of BFU-E and CFU-GM in BMSCs. FEJ could stimulate the proliferation of HSC and the differentiation of HPC to all lineages, which may thereby accelerate the recovery of hematopoietic function in myelosuppressive mice. By providing transcriptome profile we highlighted several genes and biological processes that might be applicable for FEJ to treat chemotherapy-induced myelosuppression. GO analysis showed that the co-expressed DEGs in FEJ vs model and model vs control group were involved in biological processes including ossification, osteoblast differentiation, bone mineralization and bone development. The KEGG pathway analysis pointed out ECM-receptor interaction and PI3K-AKT signaling pathway as the most relevant pathways to the function of FEJ on myelosuppression. PPI network showed MMP2 and COL1A1 were the relatively large nodes. CONCLUSION: FEJ has the hematopoietic effect in chemotherapy-induced myelosuppression mice. It might be achieved by improving the proliferative capacity of HSCs and the differentiation ability of HPCs. The molecular mode of action of FEJ might be the improvement of the bone marrow microenvironment via ECM-receptor interaction, the promoted proliferation of HSC through regulation of PI3K-AKT signaling pathway, and the involvement of osteoblasts and osteoclasts. MMP2 and COL1A1 appear to be the key relevant regulatory molecules. These results provide significant insight into the hematopoietic effects of FEJ in myelosuppression and point out novel targets for future validating analyses. CI - Copyright (c) 2019. Published by Elsevier B.V. FAU - Zhang, Yan AU - Zhang Y AD - Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China; National Engineering Research Center for Gelatin-based Traditional Chinese Medicine, Dong-E-E-Jiao Co., Ltd, Liaocheng, China. FAU - Ye, Tingting AU - Ye T AD - Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China. FAU - Hong, Zhuping AU - Hong Z AD - Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China. FAU - Gong, Shuqing AU - Gong S AD - Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China. FAU - Zhou, Xiangshan AU - Zhou X AD - National Engineering Research Center for Gelatin-based Traditional Chinese Medicine, Dong-E-E-Jiao Co., Ltd, Liaocheng, China. FAU - Liu, Haibin AU - Liu H AD - National Engineering Research Center for Gelatin-based Traditional Chinese Medicine, Dong-E-E-Jiao Co., Ltd, Liaocheng, China. FAU - Qian, Jing AU - Qian J AD - Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China. Electronic address: jingqian@zju.edu.cn. FAU - Qu, Haibin AU - Qu H AD - Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China. Electronic address: quhb@zju.edu.cn. LA - eng PT - Journal Article DEP - 20190409 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Antineoplastic Agents) RN - 0 (Drugs, Chinese Herbal) RN - U3P01618RT (Fluorouracil) SB - IM MH - Animals MH - Antineoplastic Agents/toxicity MH - Bone Marrow Cells/drug effects/metabolism MH - Drugs, Chinese Herbal/*pharmacology MH - Fluorouracil/toxicity MH - *Gene Expression Profiling MH - Gene Expression Regulation/drug effects MH - Hematopoiesis/drug effects MH - Immunocompromised Host MH - Mice MH - Mice, Inbred BALB C MH - Phosphatidylinositol 3-Kinases/metabolism MH - Random Allocation MH - Sequence Analysis, RNA MH - Specific Pathogen-Free Organisms OTO - NOTNLM OT - 5-FU OT - Fufang E'jiao Jiang OT - Myelosuppression OT - RNA-Seq OT - Signaling pathway EDAT- 2019/04/13 06:00 MHDA- 2019/12/21 06:00 CRDT- 2019/04/13 06:00 PHST- 2019/02/14 00:00 [received] PHST- 2019/03/09 00:00 [revised] PHST- 2019/04/06 00:00 [accepted] PHST- 2019/04/13 06:00 [pubmed] PHST- 2019/12/21 06:00 [medline] PHST- 2019/04/13 06:00 [entrez] AID - S0378-8741(19)30616-6 [pii] AID - 10.1016/j.jep.2019.111869 [doi] PST - ppublish SO - J Ethnopharmacol. 2019 Jun 28;238:111869. doi: 10.1016/j.jep.2019.111869. Epub 2019 Apr 9.