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Inhibitory Effects of Rutin on the Endothelial Protein C Receptor Shedding In Vitro and In Vivo

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Abstract

Endothelial cell protein C receptor (EPCR) has important functions in regulation of coagulation and inflammation. EPCR shedding from the cell surface is mediated by tumor necrosis factor-α converting enzyme (TACE). Rutin is one of the major flavonoids from the buckwheat plant Fagopyrum tataricum. In this study, we investigated the effects of rutin on phorbol-12-myristate 13-acetate (PMA), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and on cecal ligation and puncture (CLP)-mediated EPCR shedding. We used a CLP model because this model more closely resembles human sepsis. Data showed rutin was a potent inhibitor of PMA, TNF-α, IL-1β, and CLP-induced EPCR shedding by suppression of TACE expression. Treatment with rutin resulted in a decrease of PMA-stimulated phosphorylation of p38, extracellular regulated kinases 1/2, and c-Jun N-terminal kinase. These results suggest the potential application of rutin for treatment of PMA and CLP-mediated EPCR shedding.

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Acknowledgments

This study was supported by the National Research Foundation of Korea (NRF) funded by the Korea government [MSIP] (Grant no. 2013–067053).

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Authors and Affiliations

  1. Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan, 712-715, Republic of Korea

    Sae-Kwang Ku

  2. Department of Cosmetic Science and Technology, Seowon University, Cheongju, 361-742, Republic of Korea

    In-Chul Lee

  3. Laboratory for Arthritis and Bone Biology, Fatima Research Institute, Daegu Fatima Hospital, Daegu, 701-724, Republic of Korea

    Min-Su Han

  4. College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu, 702-701, Republic of Korea

    Jong-Sup Bae

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  1. Sae-Kwang Ku
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Correspondence to Jong-Sup Bae.

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Ku, SK., Lee, IC., Han, MS. et al. Inhibitory Effects of Rutin on the Endothelial Protein C Receptor Shedding In Vitro and In Vivo . Inflammation 37, 1424–1431 (2014). https://doi.org/10.1007/s10753-014-9866-5

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