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Neougonin A Inhibits Lipopolysaccharide-Induced Inflammatory Responses via Downregulation of the NF-kB Signaling Pathway in RAW 264.7 Macrophages

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Abstract

Neougonin A is a prenylated flavonoid isolated from the whole plants of Helminthostachys zeylanica (Ophioglossaceae), which was usually used as traditional Chinese herbal medicine for the treatment of fever and inflammation. In this study, the pharmacological effects and underlying molecular mechanisms of neougonin A on lipopolysaccharide (LPS)-induced inflammatory responses were investigated. We observed that neougonin A reduced the production of inflammatory mediators (TNFα, PGE2, NO, IL-1β, and IL-6; P < 0.001) and inflammation-related proteins (iNOS and COX-2) induced by LPS in murine macrophage RAW 264.7 cells. Furthermore, Western blot and immunofluorescence analysis indicated that neougonin A could inhibit the phosphorylation of IkBα and block the translocation of NF-kB/p65 into the nucleus even at 1.25 μM (P < 0.05), but have no effect on JNK, ERK1/2, and p38MAPK phosphorylation. It was suggested that the anti-inflammatory actions of neougonin A might be due to the downregulation of TNFα, IL-1β, IL-6, NO, and PGE2 via the suppression of NF-kB signal transduction pathway.

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REFERENCES

  1. Zelova, H., Z. Hanakova, Z. Cermakova, K. Smejkal, A.S. Dall, P. Babula, J. Cvacka, and J. Hosek. 2014. Evaluation of anti-inflammatory activity of prenylated substances isolated from Morus alba and Morus nigra. Journal of Natural Products 77: 1297–1303.

    Article  CAS  PubMed  Google Scholar 

  2. Hosek, J., M. Bartos, S. Chudik, S. Dall’Acqua, G. Innocenti, et al. 2011. Natural compound cudraflavone B shows promising anti-inflammatory properties in vitro. Journal of Natural Products 74: 614–619.

    Article  CAS  PubMed  Google Scholar 

  3. Jin, J.H., J.S. Kim, S.S. Kang, K.H. Son, H.W. Chang, and H.P. Kim. 2010. Anti-inflammatory and anti-arthritic activity of total flavonoids of the roots of Sophora flavescens. Journal of Ethnopharmacology 127: 589–595.

    Article  CAS  PubMed  Google Scholar 

  4. Huang, Y.C., T.L. Hwang, C.S. Chang, Y.L. Yang, C.N. Shen, W.Y. Liao, S.C. Chen, and C.C. Liaw. 2009. Anti-inflammatory flavonoids from the rhizomes of Helminthostachys zeylanica. Journal of Natural Products 72: 1273–1278.

    Article  CAS  PubMed  Google Scholar 

  5. Wun, Z.Y., C.F. Lin, W.C. Huang, Y.L. Huang, P.Y. Xu, W.T. Chang, S.J. Wu, and C.J. Liou. 2013. Anti-inflammatory effect of sophoraflavanone G isolated from Sophora flavescens in lipopolysaccharide-stimulated mouse macrophages. Food and Chemical Toxicology 62: 255–261.

    Article  CAS  PubMed  Google Scholar 

  6. Krajnovic, T., G.N. Kaludjerovic, L.A. Wessjohann, S. Mijatovic, and D. Maksimovic-Ivanic. 2016. Versatile antitumor potential of isoxanthohumol: enhancement of paclitaxel activity in vivo. Pharmacological Research 105: 62–73.

    Article  CAS  PubMed  Google Scholar 

  7. Peng, J., R.M. Hartley, G.A. Fest, and S.L. Mooberry. 2012. Amyrisins A-C, O-prenylated flavonoids from Amyris madrensis. Journal of Natural Products 75: 494–496.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sutthivaiyakit, S., O. Thongnak, T. Lhinhatrakool, O. Yodchun, R. Srimark, P. Dowtaisong, and M. Chuankamnerdkarn. 2009. Cytotoxic and antimycobacterial prenylated flavonoids from the roots of Eriosema chinense. Journal of Natural Products 72: 1092–1096.

    Article  CAS  PubMed  Google Scholar 

  9. Jung, H.A., D.M. Jeong, H.Y. Chung, H.A. Lim, J.Y. Kim, N.Y. Yoon, and J.S. Choi. 2008. Re-evaluation of the antioxidant prenylated flavonoids from the roots of Sophora flavescens. Biological & Pharmaceutical Bulletin 31: 908–915.

    Article  CAS  Google Scholar 

  10. Quan, W., H.J. Lee, C.Y. Kim, C.W. Noh, B.H. Um, M.H. Oak, and K.M. Kim. 2008. Anti-allergic prenylated flavonoids from the roots of Sophora flavescens. Planta Medica 74: 168–170.

    Article  CAS  PubMed  Google Scholar 

  11. Lou, S., Y.M. Zheng, S.L. Liu, J. Qiu, Q. Han, N. Li, Q. Zhu, P. Zhang, C. Yang, and Z. Liu. 2014. Inhibition of hepatitis C virus replication in vitro by xanthohumol, a natural product present in hops. Planta Medica 80: 171–176.

    CAS  PubMed  Google Scholar 

  12. Cho, J.K., Y.B. Ryu, M.J. Curtis-Long, J.Y. Kim, D. Kim, S. Lee, W.S. Lee, and K.H. Park. 2011. Inhibition and structural reliability of prenylated flavones from the stem bark of Morus lhou on β-secretase (BACE-1). Bioorganic & Medicinal Chemistry Letters 21: 2945–2948.

    Article  CAS  Google Scholar 

  13. Choi, E.J., H.C. Kwon, Y.C. Sohn, C.W. Nam, H.B. Park, C.Y. Kim, and H.O. Yang. 2009. Four flavonoids from Echinosophora koreensis and their effects on alcohol metabolizing enzymes. Archives of Pharmacal Research 32: 851–855.

    Article  CAS  PubMed  Google Scholar 

  14. Milligan, S., J. Kalita, V. Pocock, A. Heyerick, C.L. De, H. Rong, and K.D. De. 2002. Oestrogenic activity of the hop phyto-oestrogen, 8-prenylnaringenin. Reproduction 123: 235–242.

    Article  CAS  PubMed  Google Scholar 

  15. Omisore, N.O.A., C.O. Adewunmi, E.O. Iwalewa, B.T. Ngadjui, T.K. Adenowo, B.M. Abegaz, J.A. Ojewole, and J. Watchueng. 2005. Antitrichomonal and antioxidant activities of Dorstenia barteri and Dorstenia convexa. Brazilian Journal of Medical and Biological Research 38: 1087–1094.

    Article  CAS  PubMed  Google Scholar 

  16. Ma, H.P., L.G. Ming, B.F. Ge, Y.K. Zhai, P. Song, C.J. Xian, and K.M. Chen. 2011. Icariin is more potent than genistein in promoting osteoblast differentiation and mineralization in vitro. Journal of Cellular Biochemistry 112: 916–923.

    Article  CAS  PubMed  Google Scholar 

  17. Su, L.H., Y.P. Li, H.M. Li, W.F. Dai, D. Liu, L. Cao, and R.T. Li. 2016. Anti-inflammatory prenylated flavonoids from Helminthostachys zeylanica. Chemical & Pharmaceutical Bulletin 64: 497–501.

    Article  CAS  Google Scholar 

  18. Huang, Y.C., T.L. Hwang, Y.L. Yang, S.H. Wu, M.H. Hsu, J.P. Wang, S.C. Chen, L.J. Huang, and C.C. Liaw. 2010. Acetogenin and prenylated flavonoids from Helminthostachys zeylanica with inhibitory activity on superoxide generation and elastase release by neutrophils. Planta Medica 76: 447–453.

    Article  CAS  PubMed  Google Scholar 

  19. Ferrari, A.U., A. Radaelli, I. Mori, L. Mircoli, S. Perlini, P. Meregalli, L. Fedele, and G. Mancia. 2001. Nitric oxide-dependent vasodilation and the regulation of arterial blood pressure. Journal of Cardiovascular Pharmacology 38: S19–S22.

    Article  CAS  PubMed  Google Scholar 

  20. Tuteja, N., M. Chandra, R. Tuteja, and M.K. Misra. 2004. Nitric oxide as a unique bioactive signaling messenger in physiology and pathophysiology. Journal of Biomedicine & Biotechnology 4: 227–237.

    Article  Google Scholar 

  21. Sosroseno, W., E. Herminajeng, P.S. Bird, and G.J. Seymour. 2004. L-arginine-dependent nitric oxide production of a murine macrophage-like RAW 264.7 cell line stimulated with Porphyromonas gingivalis lipopolysaccharide. Oral Microbiology and Immunology 19: 65–70.

    Article  CAS  PubMed  Google Scholar 

  22. Bonizzi, G., and M. Karin. 2004. The two NF-kB activation pathways and their role in innate and adaptive immunity. Trends in Immunology 25: 280–288.

    Article  CAS  PubMed  Google Scholar 

  23. Iwai, K. 2012. Diverse ubiquitin signaling in NF-kB activation. Trends in Cell Biology 22: 355–364.

    Article  CAS  PubMed  Google Scholar 

  24. Chen, J.Q., and Z.J. Chen. 2013. Regulation of NF-kB by ubiquitination. Current Opinion in Immunology 25: 4–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Qi, M.S., and A.E. Elaine. 2005. MAP kinase pathways. Journal of Cell Science 118: 3569–3573.

    Article  CAS  PubMed  Google Scholar 

  26. Palanki, M.S.S. 2002. Inhibitors of AP-1 and NF-kappa B mediated transcriptional activation: therapeutic potential in autoimmune diseases and structural diversity. Current Medicinal Chemistry 9: 219–227.

    Article  CAS  PubMed  Google Scholar 

  27. Olajide, O.A., E.H. Heiss, D. Schachner, C.W. Wright, A.M. Vollmar, and V.M. Dirsch. 2007. Synthetic cryptolepine inhibits DNA binding of NF-kappaB. Bioorganic & Medicinal Chemistry 15: 43–49.

    Article  CAS  Google Scholar 

  28. Ci, X.X., R. Ren, K. Xu, H. Li, Q. Yu, Y. Song, D. Wang, R.T. Li, and X.M. Deng. 2010. Schisantherin A exhibits anti-inflammatory properties by down-regulating NF-kB and MAPK signaling pathways in lipopolysaccharide-treated RAW 264.7 Cells. Inflammation 33: 126–136.

    Article  CAS  PubMed  Google Scholar 

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ACKNOWLEDGMENTS

This research work was financially supported by the grant from the National Natural Science Foundation of China (Nos. 21572082 and 21262021), the Personnel Training Project of Yunnan, China (No. 14118650), and the Science and Technology Plan Projects of Yunnan Province (No. 1405178320)

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  1. Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, 650500, People’s Republic of China

    Lang Cao, Rongtao Li, Xuanqin Chen, Yong Xue & Dan Liu

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  1. Lang Cao
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  2. Rongtao Li
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Correspondence to Dan Liu.

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Cao, L., Li, R., Chen, X. et al. Neougonin A Inhibits Lipopolysaccharide-Induced Inflammatory Responses via Downregulation of the NF-kB Signaling Pathway in RAW 264.7 Macrophages. Inflammation 39, 1939–1948 (2016). https://doi.org/10.1007/s10753-016-0429-9

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  • DOI: https://doi.org/10.1007/s10753-016-0429-9

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