Biotransformation of artemisinin by human intestinal fungi and cytotoxicity against breast cancer cells of its metabolites

Xin He; Xuemei Wei; Zhong He; Changliang Yao; Min Nie; Xiaochi Ma; Qinhua Chen; De-An Guo

doi:10.1016/j.phytochem.2025.114551

Biotransformation of artemisinin by human intestinal fungi and cytotoxicity against breast cancer cells of its metabolites

Phytochemistry. 2025 Oct:238:114551. doi: 10.1016/j.phytochem.2025.114551. Epub 2025 May 19.

Authors

Xin He¹, Xuemei Wei², Zhong He³, Changliang Yao⁴, Min Nie⁴, Xiaochi Ma⁵, Qinhua Chen⁶, De-An Guo⁷

Affiliations

¹ School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China; National Engineering Research Center of TCM Standardization Technology, Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
² Shenzhen Baoan Authentic TCM Therapy Hospital, Shenzhen, 518101, China.
³ State Key Laboratory of Chemical Biology, Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
⁴ National Engineering Research Center of TCM Standardization Technology, Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
⁵ Pharmaceutical Research Center, Second Affiliated Hospital, Dalian Medical University, Dalian, 116023, China.
⁶ Shenzhen Baoan Authentic TCM Therapy Hospital, Shenzhen, 518101, China. Electronic address: cqh77@163.com.
⁷ School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China; National Engineering Research Center of TCM Standardization Technology, Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. Electronic address: daguo@simm.ac.cn.

PMID: 40398524
DOI: 10.1016/j.phytochem.2025.114551

Abstract

Artemisinin widely exists in the Artemisia annua L. and is the front-line of antimalarial drugs. In this study, microbial transformation of artemisinin was performed based on seventeen human intestinal fungal species. Our findings revealed that isomerization and deoxygenation were the most prevalent metabolic pathways in fungi. Incubation of artemisinin with Rhizopus microspores (PT2906) and Candida boidinii (M7017B) afforded three new compounds (P3, P5 and P6) along with seven known metabolites which were elucidated by extensive spectroscopic data analysis. All metabolites were evaluated for their cytotoxicity against MCF-7 cells, and the results showed that 3β-hydroxydeoxyartemisinin (P5) suppressed the growth of MCF-7 cells better than artemisinin. In addition, ten artemisinin isomers were found in the feces of antibiotic-treated mice after M7017B transplantation, demonstrating that human intestinal fungi have the potential to participate in the in vivo intestinal transformation of artemisinin.

Keywords: Artemisinin; Biotransformation; Cytotoxicity; Intestinal fungi.

MeSH terms

Animals
Antineoplastic Agents* / chemistry
Antineoplastic Agents* / metabolism
Antineoplastic Agents* / pharmacology
Artemisinins* / chemistry
Artemisinins* / metabolism
Artemisinins* / pharmacology
Biotransformation
Breast Neoplasms* / drug therapy
Breast Neoplasms* / pathology
Candida* / metabolism
Cell Proliferation / drug effects
Drug Screening Assays, Antitumor
Female
Fungi* / metabolism
Humans
Intestines* / microbiology
MCF-7 Cells
Mice
Molecular Structure
Rhizopus* / metabolism

Substances

Artemisinins
artemisinin
Antineoplastic Agents