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Rutin ameliorates inflammatory pain by inhibiting P2X7 receptor in mast cells

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Abstract

Rutin is a natural anti-inflammatory ingredient widely found in medicinal plants. Studies have shown that rutin inhibits mast cell degranulation and the release of inflammatory mediators. Mast cell P2X7 receptor mediates mast cell degranulation and serves as a therapeutic target for inflammatory pain. Herein, the aim of this study was to investigate whether the anti-inflammatory mechanism of rutin is related to the mast cell P2X7 receptor. Our results showed that rutin could inhibit [Ca2+]i elevation induced by 5 mM ATP or 30 μM BZATP in a concentration-dependent manner in mouse peritoneal mast cells. Rutin also suppressed the inward current mediated by P2X7 receptor. In vivo, rutin could significantly inhibit the mechanical hypersensitivity induced by 100 mM ATP that is associated with P2X7 receptor in mast cells. Moreover, molecular docking revealed the high affinity between rutin and the P2X7 receptor crystal structure. Collectively, this study demonstrated that rutin attenuated inflammatory pain by inhibiting the activity of P2X7 receptor in mast cells.

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Acknowledgements

We thank all participants for their cheerful support.

Funding

The study was financially supported by the National Natural Science Foundation of China (No. 31771163), the Key Project of Jiangsu Administration of Traditional Chinese Medicine (No. ZD202001), and Innovative Project of postgraduate education in Jiangsu Province (No. KYCX21_1745).

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Authors and Affiliations

  1. School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China

    Fan Ye, Jiahua Lv, Xinyu Shen, Jian Zhang, Yingxin Zong, Chan Zhu, Yan Yang, Keke Jia, Yucui Jiang & Zongxiang Tang

  2. School of Chinese Medicine & School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China

    Yucui Jiang

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  1. Fan Ye
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  2. Jiahua Lv
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  3. Xinyu Shen
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Contributions

Fan Ye: methodology, performed the experiment, writing—original draft. Material preparation was performed by Jiahua Lv, Xinyu Shen, and Jian Zhang. Yingxin Zong, Chan Zhu, Yan Yang, and Keke Jia collected and analyzed the data. Yucui Jiang: methodology, validation, supervision. Zongxiang Tang: project administration, funding acquisition. The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding authors

Correspondence to Yucui Jiang or Zongxiang Tang.

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Ethics approval

The Experimental Animal Ethics Committee of Nanjing University of Chinese Medicine approved the development of this animal experiment. All animal experiments conformed to the Guidelines for the Care and Use of Laboratory Animals and were approved by the Animal Ethics Committee of Nanjing University of Chinese Medicine (Ethics license ACU190601, 20,190,605).

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Key points

• Rutin inhibited intracellular calcium mobilization mediated by the P2X7 receptor.

• Rutin inhibited currents mediated by the P2X7 receptor.

• Rutin ameliorated inflammation pain mediated by the P2X7 receptor in mast cells.

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Supplementary file1 (DOCX 1332 KB)

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Ye, F., Lv, J., Shen, X. et al. Rutin ameliorates inflammatory pain by inhibiting P2X7 receptor in mast cells. J Physiol Biochem 79, 287–295 (2023). https://doi.org/10.1007/s13105-022-00938-w

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