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Regulatory effect of Yinchenhao decoction on bile acid metabolism to improve the inflammatory microenvironment of hepatocellular carcinoma in mice

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Abstract

Hepatocellular carcinoma (HCC) is a malignant tumor with extremely high mortality. The tumor microenvironment is the “soil” of its occurrence and development, and the inflammatory microenvironment is an important part of the “soil”. Bile acid is closely related to the occurrence of HCC. Bile acid metabolism disorder is not only directly involved in the occurrence and development of HCC but also affects the inflammatory microenvironment of HCC. Yinchenhao decoction, a traditional Chinese medicine formula, can regulate bile acid metabolism and may affect the inflammatory microenvironment of HCC. To determine the effect of Yinchenhao decoction on bile acid metabolism in mice with HCC and to explore the possible mechanism by which Yinchenhao decoction improves the inflammatory microenvironment of HCC by regulating bile acid metabolism, we established mice model of orthotopic transplantation of hepatocellular carcinoma. These mice were treated with three doses of Yinchenhao decoction, then liver samples were collected and tested. Yinchenhao decoction can regulate the disorder of bile acid metabolism in liver cancer mice. Besides, it can improve inflammatory reactions, reduce hepatocyte degeneration and necrosis, and even reduce liver weight and the liver index. Taurochenodeoxycholic acid, hyodeoxycholic acid, and taurohyodeoxycholic acid are important molecules in the regulation of the liver inflammatory microenvironment, laying a foundation for the regulation of the liver tumor inflammatory microenvironment based on bile acids. Yinchenhao decoction may improve the inflammatory microenvironment of mice with HCC by ameliorating hepatic bile acid metabolism.

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Abbreviations

ALT:

Alanine aminotransferase

AFP:

Alpha-fetoprotein

AST:

Aspartate transaminase

HCC:

Hepatocellular carcinoma

HDG:

Yinchenhao Decoction high-dose group

IL-6:

Interleukin-6

LDG:

Yinchenhao Decoction low-dose group

LPS:

Lipopolysaccharide

MDG:

Yinchenhao Decoction middle-dose group

MG:

The model group

SOG:

The sham operation group

TCM:

Traditional Chinese Medicine

TNF-α:

Tumor necrosis factor-α

TNF-β:

Tumor necrosis factor-β

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Acknowledgements

We would like to express our gratitude to Biotree for generously providing the complimentary online platform (https://www.biotree.cn/) for the analysis of UHPLC–MS-MS data.

Funding

The study was supported by the National Natural Science Foundation of China (No. 81904119) and the key Clinical Specialty Discipline Construction Program of Fujian, P.R.C. The study was also supported by the program of the sixth batch of reserve talents of traditional Chinese medicine in Xiamen, Fujian.

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Author notes

  1. Jian Shi and Lin Zhu have contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Department of Traditional Chinese Medicine, School of Medicine, Xiamen University, Xiamen, China

    Jian Shi, Wan-Qing Yang, Sheng-Yan Xi, Chen-Long Zhang, Peng-Fei Li, Yu-Jie Wang, Kai-Hang Guo, Chen-Rui Huang, Zhou-Xin Yu, Bao-Kang Yu, Chun-Fang Zhang & Yu-Mei Zhang

  2. Department of Traditional Chinese Medicine, Binhai County People’s Hospital, Yancheng, China

    Lin Zhu

  3. Department of Science and Education, Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, China

    Bang-Yi Tang

  4. Department of Traditional Chinese Medicine, Xiang’an Hospital of Xiamen University, Xiamen, China

    Chen-Long Zhang, Peng-Fei Li, Yu-Jie Wang, Kai-Hang Guo, Chun-Fang Zhang & Yu-Mei Zhang

  5. Central Laboratory, School of Medicine, Xiamen University, Xiamen, China

    Jing-Ru Huang

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Contributions

JS: performed research, provided, and analyzed the data, and wrote the draft paper. LZ: performed research, provided, and analyzed the data, and wrote the draft paper. JS and LZ have contributed equally to this work and share first authorship. BYT: performed experiments, Formal analysis, and edited the manuscript. WQY: performed experiments, Formal analysis, and edited the manuscript. SYX: performed experiments, Formal analysis, and edited the manuscript. CLZ: performed experiments, Formal analysis, and edited the manuscript. PFL: performed experiments, formal analysis, analyzed the data, and edited the manuscript. KHG: performed experiments, formal analysis, and edited the manuscript. JRH: performed experiments, formal analysis, and edited the manuscript. CRH: performed experiments, formal analysis, and edited the manuscript. ZXY: performed experiments, formal analysis, and edited the manuscript. BKY: performed experiments, Formal analysis, and edited the manuscript. CFZ: Methodology, designed, organized, supervised research, and identified traditional Chinese medicines. YMZ: Methodology, designed, organized, and supervised research and edited the paper. All authors contributed to the paper and approved the submitted version.

Corresponding authors

Correspondence to Chun-Fang Zhang or Yu-Mei Zhang.

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Shi, J., Zhu, L., Tang, BY. et al. Regulatory effect of Yinchenhao decoction on bile acid metabolism to improve the inflammatory microenvironment of hepatocellular carcinoma in mice. J Nat Med 78, 633–643 (2024). https://doi.org/10.1007/s11418-024-01812-3

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