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, Hongliang Xie Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University , No. 866 Yuhangtang Road, West Lake District, Hangzhou City, Zhejiang Province, 310058, China National Key Laboratory of Chinese Medicine Modernization, Innovation Center of Yangtze River Delta, Zhejiang University , No. 828 Zhongxing Road, Xitang Town, Jiaxing City, Zhejiang Province, 314100, China Search for other works by this author on: Oxford Academic Aolin Zhang Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University , No. 866 Yuhangtang Road, West Lake District, Hangzhou City, Zhejiang Province, 310058, China National Key Laboratory of Chinese Medicine Modernization, Innovation Center of Yangtze River Delta, Zhejiang University , No. 828 Zhongxing Road, Xitang Town, Jiaxing City, Zhejiang Province, 314100, China Search for other works by this author on: Oxford Academic Junwei Li Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University , No. 866 Yuhangtang Road, West Lake District, Hangzhou City, Zhejiang Province, 310058, China National Key Laboratory of Chinese Medicine Modernization, Innovation Center of Yangtze River Delta, Zhejiang University , No. 828 Zhongxing Road, Xitang Town, Jiaxing City, Zhejiang Province, 314100, China Search for other works by this author on: Oxford Academic Xuan Mou Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University , No. 866 Yuhangtang Road, West Lake District, Hangzhou City, Zhejiang Province, 310058, China National Key Laboratory of Chinese Medicine Modernization, Innovation Center of Yangtze River Delta, Zhejiang University , No. 828 Zhongxing Road, Xitang Town, Jiaxing City, Zhejiang Province, 314100, China Search for other works by this author on: Oxford Academic Tao He Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University , No. 866 Yuhangtang Road, West Lake District, Hangzhou City, Zhejiang Province, 310058, China National Key Laboratory of Chinese Medicine Modernization, Innovation Center of Yangtze River Delta, Zhejiang University , No. 828 Zhongxing Road, Xitang Town, Jiaxing City, Zhejiang Province, 314100, China Search for other works by this author on: Oxford Academic Tsz Ching Yeung Department of Obstetrics and Gynaecology; Li Ka Shing Institute of Health Sciences; School of Biomedical Sciences; Sichuan University-Chinese University of Hong Kong Joint Reproductive Medicine Laboratory, The Chinese University of Hong Kong , Shatin, New Territories, 999077, Hong Kong Search for other works by this author on: Oxford Academic Clara Bik San Lau Institute of Chinese Medicine, The Chinese University of Hong Kong , Shatin, New Territories, 999077, Hong Kong SAR, China Search for other works by this author on: Oxford Academic Zhong Zuo School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong , Shatin, New Territories, 999077, Hong Kong SAR, China Search for other works by this author on: Oxford Academic Ping Li Department of Biological Sciences, Lehman College, City University of New York , 250 Bedford Park Boulevard West, Bronx, New York, 10468, United States Search for other works by this author on: Oxford Academic Edward J Kennelly Department of Biological Sciences, Lehman College, City University of New York , 250 Bedford Park Boulevard West, Bronx, New York, 10468, United States Search for other works by this author on: Oxford Academic
https://orcid.org/0000-0002-8261-078X , Ping Chung Leung Institute of Chinese Medicine, The Chinese University of Hong Kong , Shatin, New Territories, 999077, Hong Kong SAR, China Search for other works by this author on: Oxford Academic Yu Tang Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University , No. 866 Yuhangtang Road, West Lake District, Hangzhou City, Zhejiang Province, 310058, China National Key Laboratory of Chinese Medicine Modernization, Innovation Center of Yangtze River Delta, Zhejiang University , No. 828 Zhongxing Road, Xitang Town, Jiaxing City, Zhejiang Province, 314100, China Search for other works by this author on: Oxford Academic Xiaohui Fan Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University , No. 866 Yuhangtang Road, West Lake District, Hangzhou City, Zhejiang Province, 310058, China National Key Laboratory of Chinese Medicine Modernization, Innovation Center of Yangtze River Delta, Zhejiang University , No. 828 Zhongxing Road, Xitang Town, Jiaxing City, Zhejiang Province, 314100, China Engineering Research Center of Innovative Anticancer Drugs, Ministry of Education , No. 866 Yuhangtang Road, West Lake District, Hangzhou City, Zhejiang Province, 310058, China Modern Chinese Medicine and Reproductive Health Joint Innovation Center , Innovation Center of Yangtze River Delta, No. 828 Zhongxing Road, Xitang Town, Jiaxing City, Zhejiang Province, 314100, China Search for other works by this author on: Oxford Academic Chi Chiu Wang Department of Obstetrics and Gynaecology; Li Ka Shing Institute of Health Sciences ; School of Biomedical Sciences; Sichuan University-Chinese University of Hong Kong Joint Reproductive Medicine Laboratory, The Chinese University of Hong Kong , Shatin, New Territories, 999077, Hong Kong Modern Chinese Medicine and Reproductive Health Joint Innovation Center , Innovation Center of Yangtze River Delta, No. 828 Zhongxing Road, Xitang Town, Jiaxing City, Zhejiang Province, 314100, China College of Basic Medical Sciences, Zhejiang Chinese Medical University , No. 548 Binwen Road, Binjiang District, Hangzhou City, Zhejiang Province, 310053, China Search for other works by this author on: Oxford Academic Lu Li Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University , No. 866 Yuhangtang Road, West Lake District, Hangzhou City, Zhejiang Province, 310058, China National Key Laboratory of Chinese Medicine Modernization, Innovation Center of Yangtze River Delta, Zhejiang University , No. 828 Zhongxing Road, Xitang Town, Jiaxing City, Zhejiang Province, 314100, China Department of Obstetrics and Gynaecology; Li Ka Shing Institute of Health Sciences ; School of Biomedical Sciences; Sichuan University-Chinese University of Hong Kong Joint Reproductive Medicine Laboratory, The Chinese University of Hong Kong , Shatin, New Territories, 999077, Hong Kong Institute of Chinese Medicine, The Chinese University of Hong Kong , Shatin, New Territories, 999077, Hong Kong SAR, China Modern Chinese Medicine and Reproductive Health Joint Innovation Center , Innovation Center of Yangtze River Delta, No. 828 Zhongxing Road, Xitang Town, Jiaxing City, Zhejiang Province, 314100, China Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital , Zhejiang University School of Medicine; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, No. 3 Qingchun East Road, Shangcheng District, Hangzhou City, Zhejiang Province, 310016, China Corresponding author: Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, No. 866 Yuhangtang Road, West Lake District, Hangzhou City, Zhejiang Province, 310058, China. Email: luciali@zju.edu.cn Search for other works by this author on: Oxford Academic
Toxicology Research, Volume 13, Issue 2, April 2024, tfae057, https://doi.org/10.1093/toxres/tfae057
Published:
13 April 2024
Article history
Received:
12 January 2024
Revision received:
19 March 2024
Accepted:
02 April 2024
Published:
13 April 2024
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Hongliang Xie, Aolin Zhang, Junwei Li, Xuan Mou, Tao He, Tsz Ching Yeung, Clara Bik San Lau, Zhong Zuo, Ping Li, Edward J Kennelly, Ping Chung Leung, Yu Tang, Xiaohui Fan, Chi Chiu Wang, Lu Li, Cycasin derivative: a potential embryotoxic component of Atractylodes macrocephala rhizome for limb malformation, Toxicology Research, Volume 13, Issue 2, April 2024, tfae057, https://doi.org/10.1093/toxres/tfae057
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Abstract
Objective
The rhizome of Atractylodes macrocephala Koidz. (Asteraceae), called Atractylodes macrocephala rhizome (AMR) and known by its traditional name Bai Zhu, is a prominent Chinese herbal medicine employed for preventing miscarriage. However, our previous study revealed that high dosages of AMR administered during pregnancy could cause embryotoxicity but the specific embryotoxic components and their underlying mechanisms remain unclear. This study aimed to screen and identify the potential embryotoxic components of AMR.
Methods
The AMR extracts and sub-fractions were analyzed by thin layer chromatography and subsequently screened by in vitro mouse limb bud micromass and mouse whole embryo culture bioassays. The embryotoxic fractions from AMR were further evaluated in vivo using a pregnant mouse model. The structures of the potential embryotoxic components were analyzed using matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS).
Results
In vitro and in vivo bioassays revealed that AMR glycoside-enriched sub-fractions (AMR-A-IIa and AMR-A-IIb) exhibited potential embryotoxicity. These sub-fractions, when administered to pregnant animals, increased the incidence of stillbirth and congenital limb malformations. MS spectrometry analysis identified cycasin derivatives in both sub-fractions, suggesting their possible role in the observed limb malformations. However, further experiments are necessary to validate this hypothesis and to elucidate the underlying mechanisms.
Conclusions
Our study provides significant scientific evidence on the pharmacotoxicity of AMR, which is important for the safe clinical application of commonly used Chinese herbal medicines during pregnancy.
Graphical Abstract
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Chinese herbal medicine, Atractylodes macrocephala rhizome, embryotoxic components, cycasin derivative, safety evaluation
© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com
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