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New podolactones from the seeds of Podocarpus nagi and their anti-inflammatory effect

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Abstract

Podolactones are a class of structural diverse diterpenoid lactones, mainly isolated from the Podocarpus species. Several bioactivities have been disclosed for podolactones, including cytotoxicity and anti-atherosclerosis. In this study, the seeds of P. nagi were isolated by comprehensive chromatographic methods to obtain three new podolatones, named nagilactone B 1-O-β-d-glucoside (1), nagilactone N3 3-O-β-d-glucoside (2), and 2-epinagilactone B (3), as well as a known compound, nagilactone B (4). Their structures were determined by analyses of NMR and HRESIMS data. Compounds 1 and 2 significantly inhibited nitric oxide (NO) production on LPS-stimulated RAW264.7 macrophages, with IC50 values of 0.18 ± 0.04 and 0.53 ± 0.03 μM, respectively. Indomethacin (IC50 4.21 ± 0.32 μM) was used as a positive control. Compound 1 suppressed the expression of inducible NO synthase (iNOS) in a concentration-dependent manner, mediating through inhibiting nuclear factor-κB (NF-κB) activity. This is the first report regarding the anti-inflammatory effect of podolactones, which could be potential anti-inflammatory agents.

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References

  1. Barrero AF, Quilez del Moral JF, Herrador MM (2003) Podolactones: a group of biologically active norditerpenoids. In: Atta-ur-Rahman (ed) Studies in natural products chemistry. Elsevier, Amsterdam, pp 453‒516

  2. Abdillahi HS, Finnie JF, Van Staden J (2011) Anti-inflammatory, antioxidant, anti-tyrosinase and phenolic contents of four Podocarpus species used in traditional medicine in South Africa. J Ethnopharmacol 136:496–503. https://doi.org/10.1016/j.jep.2010.07.019

    Article  PubMed  CAS  Google Scholar 

  3. Zheng YD, Guan XC, Li D, Wang AQ, Ke CQ, Tang CP, Lin LG, Ye Y, Wang ZL, Yao S (2016) Novel diterpenoids from the twigs of Podocarpus nagi. Molecules 21:1282. https://doi.org/10.3390/molecules21101282

    Article  CAS  Google Scholar 

  4. Feng ZL, Zhang LL, Zheng YD, Liu QY, Liu JX, Feng L, Huang L, Zhang QW, Lu JJ, Lin LG (2017) Norditerpenoids and dinorditerpenoids from the seeds of Podocarpus nagi as cytotoxic agents and autophagy inducers. J Nat Prod 80:2110–2117. https://doi.org/10.1021/acs.jnatprod.7b00347

    Article  PubMed  CAS  Google Scholar 

  5. Gui Y, Yao S, Yan H, Hu L, Yu C, Gao F, Xi C, Li H, Ye Y, Wang YP (2016) A novel small molecule liver X receptor transcriptional regulator, nagilactone B, suppresses atherosclerosis in apoE-deficient mice. Cardiovasc Res 112:502–514. https://doi.org/10.1093/cvr/cvw183

    Article  PubMed  CAS  Google Scholar 

  6. Zhang ML, Ying BP, Kubo I (1992) Nagilactones from Podocarpus nagi and their effects on the feeding and growth of tobacco budworm. J Nat Prod 55:1057–1062. https://doi.org/10.1021/Np50086a004

    Article  CAS  Google Scholar 

  7. Liu QY, Li D, Wang AQ, Dong Z, Yin S, Zhang QW, Ye Y, Li LC, Lin LG (2016) Nitric oxide inhibitory xanthones from the pericarps of Garcinia mangostana. Phytochemistry 131:115–123. https://doi.org/10.1016/j.phytochem.2016.08.007

    Article  PubMed  CAS  Google Scholar 

  8. Li D, Liu QY, Sun W, Chen XP, Wang Y, Sun YX, Lin LG (2018) 1,3,6,7-Tetrahydroxy-8-prenylxanthone ameliorates inflammatory responses resulted in by the paracrine interaction of adipocytes and macrophages. Br J Pharmacol 175:1590–1606. https://doi.org/10.1111/bph.14162

    Article  PubMed  CAS  Google Scholar 

  9. Feng ZL, Li D, Liu QY, Liu JX, Huang L, Zhang QW, Wang YT, Lin LG (2017) Anti-inflammatory abietane diterpenoids from the seeds of Podocarpus nagi. Phytochem Lett 21:260–263. https://doi.org/10.1016/j.phytol.2017.07.011

    Article  CAS  Google Scholar 

  10. Niu B, Ke CQ, Li BH, Li YY, Yi YJ, Luo YW, Shuai L, Yao S, Lin LG, Li J, Ye Y (2017) Cucurbitane glucosides from the crude extract of Siraitia grosvenorii with moderate effects on PGC-1α promoter activity. J Nat Prod 80:1428–1435. https://doi.org/10.1021/acs.jnatprod.6b01086

    Article  PubMed  CAS  Google Scholar 

  11. Hayashi Y, Matsumoto T, Uemura M, Koreeda M (1980) Carbon-13 NMR studies of the biologically active nor-diterpenoid dilactones from Podocarpus plants. Org Magn Reson 14:86–91

    Article  CAS  Google Scholar 

  12. Hayashi Y, Takahashi S, Ona H, Sakan T (1969) Structures of nagilactone a, b, c, and d, novel nor-and bisnorditerpenoids. Tetrahedron Lett 9:2071–2076

    Article  Google Scholar 

  13. Ye Y, Yang YP, Yao S, Ma YL, Tang CP, Zhao J, Ke CQ, Xu WW (2016) Nagilactone compounds having antilipemic activity, preparation method therefor and uses thereof. WIPO Patent Application WO/2016/131426

  14. Hayashi Y, Yo-ichi Y, Matsumoto T (1977) New congeners of cytotoxic nor-diterpenoid dilactones in Podocarpus nagi: two C19 lactones from seed extract. Tetrahedron Lett 18:3637–3640

    Article  Google Scholar 

  15. Yuan M, Konstantopoulos N, Lee J, Hansen L, Li ZW, Karin M, Shoelson SE (2001) Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science 293:1673–1677. https://doi.org/10.1126/science.1061620

    Article  PubMed  CAS  Google Scholar 

  16. Bao H, Zhang LL, Liu QY, Feng L, Ye Y, Lu JJ, Lin LG (2016) Cytotoxic and pro-apoptotic effects of cassane diterpenoids from the seeds of Caesalpinia sappan in cancer cells. Molecules 21:791. https://doi.org/10.3390/molecules21060791

    Article  CAS  Google Scholar 

  17. Xu XH, Liu QY, Li T, Liu JL, Chen X, Huang L, Qiang WA, Chen X, Wang Y, Lin LG, Lu JJ (2017) Garcinone E induces apoptosis and inhibits migration and invasion in ovarian cancer cells. Sci Rep 7:10718. https://doi.org/10.1038/s41598-017-11417-4

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Financial support by Science and Technology Development Fund, Macao S.A.R (FDCT 102/2017/A), the Research Fund of University of Macau (MYRG2017-00109-ICMS), and the State Key Laboratory of Drug Research (SIMM1803KF-16) are gratefully acknowledged.

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Correspondence to Li-Gen Lin.

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Feng, ZL., Zhang, T., Liu, JX. et al. New podolactones from the seeds of Podocarpus nagi and their anti-inflammatory effect. J Nat Med 72, 882–889 (2018). https://doi.org/10.1007/s11418-018-1219-5

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  • DOI: https://doi.org/10.1007/s11418-018-1219-5

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