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Inhibitory Effects of Emodin, Thymol, and Astragalin on Leptospira interrogans-Induced Inflammatory Response in the Uterine and Endometrium Epithelial Cells of Mice

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Abstract

Leptospirosis is a systemic infection that causes, among others, acute kidney injury, acute liver disease, muscle pain, vasculitis, bleeding disorders, and reproductive loss. In an effort to reduce uterine inflammatory responses induced by Leptospira, we evaluated the anti-inflammation effects of emodin, thymol, and astragalin in a mouse model. Our results showed that treatment with emodin, thymol, and astragalin alleviated uterine inflammation induced by leptospira infection via suppression of pro-inflammatory cytokine expression and prevented tissue damage. Furthermore, we used primary endometrium epithelial cells to show that treatment with these chemicals inhibited the expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 using enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. Western blot results showed that these chemicals suppressed the phosphorylation of p38, p65, extracellular signal-regulated kinase, and c-Jun N-terminal kinase. These results indicate that treatment with emodin, thymol, and astragalin suppressed inflammatory response by regulating NF-κB and mitogen-activated protein kinase signaling pathways in leptospira-infected uterine and endometrium epithelial cells of mice.

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Acknowledgements

We thank Dr. Xiaokui Guo for providing Leptospira interrogans serovar Autumnalis. This work was supported by the National Natural Science Foundation of China (No. 31572582) to YC, the Key Project of Chinese National Programs for Research and Development (No. 2016YFD0501005) to YC YF, and the Special Fund for Agro-Scientific Research in the Public Interest of the People’s Republic of China (No. 201303042) to ZD YC.

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    Authors and Affiliations

    1. Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, 130062, People’s Republic of China

      Wenlong Zhang, Xiaojie Lu, Wei Wang, Yunhe Fu, Xiaofei Zhou, Naisheng Zhang & Yongguo Cao

    2. Department of Infectious Disease, College of Veterinary Medicine, Jilin University, Changchun, 130062, People’s Republic of China

      Zhuang Ding

    3. Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, 130062, People’s Republic of China

      Yongguo Cao

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    1. Wenlong Zhang
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    Correspondence to Yongguo Cao.

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    All animal experiments followed the regulations for the Administration of Affairs Concerning Experimental Animals in China. The protocol was approved by the Committee on the Ethics of Animal Experiments of the First Norman Bethune Hospital of Jilin University, China ((2013) clinical trial (2013–121)).

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    The authors declare that they have no conflict of interest.

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    Wenlong Zhang and Xiaojie Lu contributed equally to this work.

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    Zhang, W., Lu, X., Wang, W. et al. Inhibitory Effects of Emodin, Thymol, and Astragalin on Leptospira interrogans-Induced Inflammatory Response in the Uterine and Endometrium Epithelial Cells of Mice. Inflammation 40, 666–675 (2017). https://doi.org/10.1007/s10753-017-0513-9

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