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Deciphering the pharmacological mechanism of Guan-Jie-Kang in treating rat adjuvant-induced arthritis using omics analysis

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Abstract

Traditional Chinese medicine (TCM) formulas have attracted increasing attention worldwide in the past few years for treating complex disease including rheumatoid arthritis. However, their mechanisms are complex and remain unclear. Guan-Jie-Kang (GJK), a prescription modified from “Wu Tou Decoction,” was found to significantly relieve arthritis symptoms in rats with adjuvant-induced arthritis after 30-day treatment, especially in the 24 g/kg/day group. By analyzing 1749 targets related to 358 compounds in the five herbs of GJK, we identified the possible anti-arthritis pathways of GJK, including the calcium signaling and metabolic pathways. Bone damage levels were assessed by micro-computed tomography, and greater bone protective effect was observed with GJK treatment than with methotrexate. Receptor activator of nuclear factor κB ligand (RANKL)-RANK signaling, which is related to calcium signaling, was significantly regulated by GJK. Moreover, a target metabolomics assay of serum was conducted; 17 metabolic biomarkers showed significant correlations with treatment. An integrated pathway analysis revealed that pyruvate metabolism, purine metabolism, and glycolysis metabolism were significantly associated with the effects of GJK in arthritis treatment. Thus, this study establishes a new omics analytical method integrated with bioinformatics analysis for elucidating the multi-pathway mechanisms of TCM.

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Acknowledgements

This work was financially supported by grants from the Macau Science and Technology Development Fund (No. 102/2016/A3).

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Quality Research in Chinese Medicine/Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, China

    Hudan Pan, Yanfang Zheng, Zhongwen Yuan, Rutong Ren, Hua Zhou, Ying Xie & Liang Liu

  2. Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China

    Yanfang Zheng

  3. International Institute for Translational Research of Traditional Chinese Medicine of Guangzhou University of Chinese Medicine, Guangzhou, 510006, China

    Zhongqiu Liu

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  1. Hudan Pan
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  2. Yanfang Zheng
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Correspondence to Ying Xie or Liang Liu.

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Hudan Pan, Yanfang Zheng, Zhongqiu Liu, Zhongwen Yuan, Rutong Ren, Hua Zhou, Ying Xie, and Liang Liu declare that they have no conflicts of interest. All institutional and national guidelines for the care and use of laboratory animals were followed.

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Pan, H., Zheng, Y., Liu, Z. et al. Deciphering the pharmacological mechanism of Guan-Jie-Kang in treating rat adjuvant-induced arthritis using omics analysis. Front. Med. 13, 564–574 (2019). https://doi.org/10.1007/s11684-018-0676-2

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  • DOI: https://doi.org/10.1007/s11684-018-0676-2

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