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Inhibitory Effects of JEUD-38, a New Sesquiterpene Lactone from Inula japonica Thunb, on LPS-Induced iNOS Expression in RAW264.7 Cells

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ABSTRACT

We isolated JEUD-38, a new sesquiterpene lactone from Inula japonica Thunb. JEUD-38 dramatically attenuated lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Consistent with this finding, the protein expression of inducible nitric oxide synthase (iNOS) was blocked by JEUD-38 in a concentration-dependent manner. To elucidate the mechanism, we examined the effect of JEUD-38 on LPS-stimulated nuclear factor-κB (NF-κB) nuclear translocation, inhibitory factor-κB (IκB) phosphorylation, and degradation. JEUD-38 reduced the translocation of p65, via abrogating IκB-α phosphorylation and degradation. In addition, JEUD-38 inhibited LPS-stimulated phosphorylation of mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38. Since iNOS as well as the upstream NF-κB and MAPKs are known to be closely involved in inflammation, these results suggest that JEUD-38 is a promising candidate for prevention and therapy of inflammatory diseases.

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ACKNOWLEDGMENTS

This study was supported by a grant from the National Natural Science Foundation of China (81373441, 81202542, 81402802), the Natural Science Foundation of Tian** (12JCZDJC25800, 13JCYBJC24800), the New Teachers’ Fund for Doctor Stations from Ministry of Education, China (20121202120009), the Project Sponsored by the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry, a grant from “211” project of Tian** Medical University, and a grant from Japan Society for the Promotion of Science (FY2013, BR131302).

Conflict of Interest

There is no conflict of interest for all authors of this manuscript.

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Authors and Affiliations

  1. Tian** Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tian** Medical University, Tian**, 300070, China

    **aoqing Wang, Sheng-An Tang, Ran Wang, Yuling Qiu, Meihua ** & Dexin Kong

  2. Department of Pharmacy, Second Hospital of Tian** Medical University, Tian**, 300211, China

    **aoqing Wang

  3. Research Center of Basic Medical Sciences, Tian** Medical University, Tian**, 300070, China

    Dexin Kong

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  1. **aoqing Wang
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  2. Sheng-An Tang
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  3. Ran Wang
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  5. Meihua **
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  6. Dexin Kong
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Correspondence to Meihua ** or Dexin Kong.

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Wang, X., Tang, SA., Wang, R. et al. Inhibitory Effects of JEUD-38, a New Sesquiterpene Lactone from Inula japonica Thunb, on LPS-Induced iNOS Expression in RAW264.7 Cells. Inflammation 38, 941–948 (2015). https://doi.org/10.1007/s10753-014-0056-2

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