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The anti-inflammatory effects of formononetin and ononin on lipopolysaccharide-induced zebrafish models based on lipidomics and targeted transcriptomics

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Abstract

Introduction

Formononetin (MBHS) and its glycosylated derivative ononin (MBHG), as the major isoflavones, have exhibited the anti-inflammatory impacts on the lipopolysaccharide (LPS)-induced inflammation. Although various researches have focused on interpreting the pharmaceutical activities of MBHG and MBHS, the molecular mechanisms in zebrafish models are still unclear.

Objective

The purpose of the present work is to investigate the molecular mechanisms of the anti-inflammatory effects of MGHG and MBHS based on lipidomics and targeted transcriptomics.

Methods

UHPLC-MS was applied for the lipid analyses and RT-PCR was adopted for the mRNA analyses, and the results of different groups were compared for exploring the significantly changed lipids and mRNAs.

Results

The results of lipidomics revealed that phosphatidylcholines (PCs) were drastically down-regulated in the MBHG or MBHS treated LPS-induced inflammatory zebrafish models. Besides, MBHS can also decrease the levels of triacylglycerols (TAGs). For the targeted transcriptomics analyses, 4 cytokines (TNF-α, IL-1β, IL-6 and IFN-γ) and 3 mRNA (JNK1, ERK1 and p38a) involved in the MAPK pathway were down-regulated and IL-10 was up-regulated under the treatment of MBHG or MBHS.

Conclusion

Combining the results of lipidomics and targeted transcriptomics, we indicated that MBHG and MBHS exerted potent anti-inflammatory effects on the LPS-induced zebrafish models through the MyD88 or TRIF MAPK/ERK and MAPK/JNK pathways and the glycerophospholipid, glycosylphosphatidylinositol (GPI)-anchor biosynthesis and glycerolipid metabolisms. Our results provided new insights into the anti-inflammatory mechanisms of MBHG or MBHS and supplied an effective method to interpret the pharmacological mechanisms of drugs.

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Acknowledgements

This work was supported by Major International S&T Cooperation Project from Ministry of Science and Technology of the People’s Republic of China (2016YFE0129000) and Fundamental Research Funds for the Central Public Welfare Research Institutes (No. ZZ10-007).

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Authors and Affiliations

  1. School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China

    Liyu Luo & Wenyuan Gao

  2. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China

    Junyi Zhou & Haiyu Zhao

  3. Beijing Key Laboratory of Analysis and Evaluation on Chinese Medicine, Beijing Institute of Drug Control, Beijing, 102206, China

    Miaoxuan Fan

Authors
  1. Liyu Luo
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  2. Junyi Zhou
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  3. Haiyu Zhao
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  4. Miaoxuan Fan
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  5. Wenyuan Gao
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Contributions

LL, HZ, MF and WG designed the study. LL and JZ were responsible for doing the experiments and analyzing the data. LL wrote the article. HZ, MF and WG revised the manuscript.

Corresponding authors

Correspondence to Miaoxuan Fan or Wenyuan Gao.

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The authors declare that they have no conflict of interest.

Ethical approval

The experiments based on zebrafish samples were performed in accordance with the guidelines from the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) approved by Hunter Biotechnology Co. Ltd. (Hangzhou, China) with the Approval Number as SYXK 2012-0171.

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Luo, L., Zhou, J., Zhao, H. et al. The anti-inflammatory effects of formononetin and ononin on lipopolysaccharide-induced zebrafish models based on lipidomics and targeted transcriptomics. Metabolomics 15, 153 (2019). https://doi.org/10.1007/s11306-019-1614-2

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