Nepetin, a natural compound from Inulae flos, suppresses degranulation and eicosanoid generation through PLCγ1 and Akt signaling pathways in mast cells

Ji, Ning; Kim, Sun-Gun; Park, Hyo-Hyun; Lee, Eujin; Lee, Youn Ju; Jin, Meihua; Lee, Eunkyung

doi:10.1007/s12272-020-01212-7

Research Article
Published: 03 February 2020

Nepetin, a natural compound from Inulae flos, suppresses degranulation and eicosanoid generation through PLCγ1 and Akt signaling pathways in mast cells

Ning Ji¹,
Sun-Gun Kim²,
Hyo-Hyun Park²,
Eujin Lee²,
Youn Ju Lee³,
Meihua Jin¹ &
Eunkyung Lee²

Archives of Pharmacal Research volume 43, pages 224–232 (2020)Cite this article

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Abstract

Nepetin derived from the flowers of Inula japonica, Inulae flos, has been reported to exert several biological activities, including anti-inflammatory responses. In this study, we evaluated the anti-allergic property of nepetin with its molecular mechanisms in bone marrow-derived mast cells (BMMC) and mice. In this in vitro study, we investigated the inhibitory effects of nepetin on degranulation and generation of leukotriene C₄ (LTC₄) and prostaglandin D₂ (PGD₂) in IgE/antigen (Ag)-stimulated BMMC. The effect of nepetin on passive cutaneous anaphylaxis (PCA) reaction was also studied in mice. Nepetin reduced degranulation and LTC₄ generation in BMMC. The IgE/Ag-mediated signaling pathway demonstrated that nepetin suppressed intracellular Ca²⁺ level and activation of PLCγ1 and cPLA₂. However, MAPKs were not affected by nepetin in BMMC. In addition, nepetin treatment reduced PGD₂ production and suppressed cyclooxygenase-2 protein expression via the inhibition of the Akt and nuclear factor-κB signaling pathways. With respect to the local allergic response in vivo, oral administration of nepetin suppressed mast cell-dependent PCA reaction in a dose-dependent manner. The results of this study suggest that nepetin might have an anti-allergic potential related to mast cell-mediated inflammatory diseases.

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Acknowledgements

This work was supported by Grants from Traditional Korean Medicine R&D Project (HI13C0538), Ministry of Health & Welfare, Republic of Korea and the National Natural Science Foundation of China (81672809).

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Affiliations

Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, People’s Republic of China
Ning Ji & Meihua Jin
Department of Korean Medicine Development, National Institute for Korean Medicine Development, Gyeongsan, 38540, Republic of Korea
Sun-Gun Kim, Hyo-Hyun Park, Eujin Lee & Eunkyung Lee
School of Medicine, Catholic University of Daegu, Daegu, 42472, Republic of Korea
Youn Ju Lee

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Ning Ji
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Sun-Gun Kim
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Hyo-Hyun Park
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Eujin Lee
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Youn Ju Lee
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Meihua Jin
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Eunkyung Lee
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Correspondence to Meihua Jin or Eunkyung Lee.

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Ji, N., Kim, SG., Park, HH. et al. Nepetin, a natural compound from Inulae flos, suppresses degranulation and eicosanoid generation through PLCγ1 and Akt signaling pathways in mast cells. Arch. Pharm. Res. 43, 224–232 (2020). https://doi.org/10.1007/s12272-020-01212-7

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Received: 30 August 2019
Accepted: 20 January 2020
Published: 03 February 2020
Issue Date: February 2020
DOI: https://doi.org/10.1007/s12272-020-01212-7

Keywords

Nepetin
BMMC
Anti-inflammatory
Passive cutaneous anaphylaxis (PCA)