Ex vivo and in vivo chemoprotective activity and potential mechanism of Martynoside against 5-fluorouracil-induced bone marrow cytotoxicity
Martynoside (MAR) is a bioactive glycoside of Rehmannia glutinosa, a traditional Chinese herb frequently prescribed for treating chemotherapy-induced pancytopenia. Despite its clinical usage in China for thousands of years, the mechanism of MAR’s hematopoietic activity and its impact on chemotherapy...
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Elsevier
2021-06-01
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Series: | Biomedicine & Pharmacotherapy |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332221002869 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mengying Hong Dongdong Chen Zhuping Hong Kejun Tang Yuanyuan Yao Liubo Chen Tingting Ye Jing Qian Yushen Du Ren Sun |
spellingShingle |
Mengying Hong Dongdong Chen Zhuping Hong Kejun Tang Yuanyuan Yao Liubo Chen Tingting Ye Jing Qian Yushen Du Ren Sun Ex vivo and in vivo chemoprotective activity and potential mechanism of Martynoside against 5-fluorouracil-induced bone marrow cytotoxicity Biomedicine & Pharmacotherapy Martynoside 5-fluorouracil Bone marrow cytotoxicity Chemoprotective activity mRNA-Seq |
author_facet |
Mengying Hong Dongdong Chen Zhuping Hong Kejun Tang Yuanyuan Yao Liubo Chen Tingting Ye Jing Qian Yushen Du Ren Sun |
author_sort |
Mengying Hong |
title |
Ex vivo and in vivo chemoprotective activity and potential mechanism of Martynoside against 5-fluorouracil-induced bone marrow cytotoxicity |
title_short |
Ex vivo and in vivo chemoprotective activity and potential mechanism of Martynoside against 5-fluorouracil-induced bone marrow cytotoxicity |
title_full |
Ex vivo and in vivo chemoprotective activity and potential mechanism of Martynoside against 5-fluorouracil-induced bone marrow cytotoxicity |
title_fullStr |
Ex vivo and in vivo chemoprotective activity and potential mechanism of Martynoside against 5-fluorouracil-induced bone marrow cytotoxicity |
title_full_unstemmed |
Ex vivo and in vivo chemoprotective activity and potential mechanism of Martynoside against 5-fluorouracil-induced bone marrow cytotoxicity |
title_sort |
ex vivo and in vivo chemoprotective activity and potential mechanism of martynoside against 5-fluorouracil-induced bone marrow cytotoxicity |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2021-06-01 |
description |
Martynoside (MAR) is a bioactive glycoside of Rehmannia glutinosa, a traditional Chinese herb frequently prescribed for treating chemotherapy-induced pancytopenia. Despite its clinical usage in China for thousands of years, the mechanism of MAR’s hematopoietic activity and its impact on chemotherapy-induced antitumor activity are still unclear. Here, we showed that MAR protected ex vivo bone marrow cells from 5-fluorouracil (5-FU)-induced cell death and inflammation response by down-regulating the TNF signaling pathway, in which II1b was the most regulatory gene. Besides, using mouse models with melanoma and colon cancer, we further demonstrated that MAR had protective effects against 5-FU-induced myelosuppression in mice without compromising its antitumor activity. Our results showed that MAR increased the number of bone marrow nucleated cells (BMNCs) and the percentage of leukocyte and granulocytic populations in 5-FU-induced myelosuppressive mice, accompanied by an increase in numbers of circulating white blood cells and platelets. The transcriptome profile of BMNCs further showed that the mode of action of MAR might be associated with the increased survival of BMNCs and the improvement of the bone marrow microenvironment. In summary, we revealed the potential molecular mechanism of MAR to counteract 5-FU-induced bone marrow cytotoxicity both ex vivo and in vivo, and highlighted its potential clinical usage in cancer patients experiencing chemotherapy-induced multi-lineage myelosuppression. |
topic |
Martynoside 5-fluorouracil Bone marrow cytotoxicity Chemoprotective activity mRNA-Seq |
url |
http://www.sciencedirect.com/science/article/pii/S0753332221002869 |
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doaj-5cc5b60917ba41138faabec688b1a80f2021-05-20T07:45:14ZengElsevierBiomedicine & Pharmacotherapy0753-33222021-06-01138111501Ex vivo and in vivo chemoprotective activity and potential mechanism of Martynoside against 5-fluorouracil-induced bone marrow cytotoxicityMengying Hong0Dongdong Chen1Zhuping Hong2Kejun Tang3Yuanyuan Yao4Liubo Chen5Tingting Ye6Jing Qian7Yushen Du8Ren Sun9Cancer Institute, The Second Affiliated Hospital, ZJU-UCLA Joint Center for Medical Education and Research, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, ChinaCancer Institute, The Second Affiliated Hospital, ZJU-UCLA Joint Center for Medical Education and Research, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, ChinaPharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang Province, ChinaCancer Institute, The Second Affiliated Hospital, ZJU-UCLA Joint Center for Medical Education and Research, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, ChinaDepartment of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, ChinaCancer Institute, The Second Affiliated Hospital, ZJU-UCLA Joint Center for Medical Education and Research, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, ChinaPharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang Province, ChinaPharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang Province, ChinaCancer Institute, The Second Affiliated Hospital, ZJU-UCLA Joint Center for Medical Education and Research, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA; Corresponding authors at: Cancer Institute, The Second Affiliated Hospital, ZJU-UCLA Joint Center for Medical Education and Research, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.Cancer Institute, The Second Affiliated Hospital, ZJU-UCLA Joint Center for Medical Education and Research, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Corresponding authors at: Cancer Institute, The Second Affiliated Hospital, ZJU-UCLA Joint Center for Medical Education and Research, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.Martynoside (MAR) is a bioactive glycoside of Rehmannia glutinosa, a traditional Chinese herb frequently prescribed for treating chemotherapy-induced pancytopenia. Despite its clinical usage in China for thousands of years, the mechanism of MAR’s hematopoietic activity and its impact on chemotherapy-induced antitumor activity are still unclear. Here, we showed that MAR protected ex vivo bone marrow cells from 5-fluorouracil (5-FU)-induced cell death and inflammation response by down-regulating the TNF signaling pathway, in which II1b was the most regulatory gene. Besides, using mouse models with melanoma and colon cancer, we further demonstrated that MAR had protective effects against 5-FU-induced myelosuppression in mice without compromising its antitumor activity. Our results showed that MAR increased the number of bone marrow nucleated cells (BMNCs) and the percentage of leukocyte and granulocytic populations in 5-FU-induced myelosuppressive mice, accompanied by an increase in numbers of circulating white blood cells and platelets. The transcriptome profile of BMNCs further showed that the mode of action of MAR might be associated with the increased survival of BMNCs and the improvement of the bone marrow microenvironment. In summary, we revealed the potential molecular mechanism of MAR to counteract 5-FU-induced bone marrow cytotoxicity both ex vivo and in vivo, and highlighted its potential clinical usage in cancer patients experiencing chemotherapy-induced multi-lineage myelosuppression.http://www.sciencedirect.com/science/article/pii/S0753332221002869Martynoside5-fluorouracilBone marrow cytotoxicityChemoprotective activitymRNA-Seq |