Advertisement

Medicinal Chemistry Research

, Volume 28, Issue 10, pp 1628–1632 | Cite as

FOXO signal activating alkaloids isolated from Ochrosia elliptica leaf cultivated in Egypt

  • Rola M. LabibEmail author
  • Fazila Zulfiqar
  • Mohamed A. Ibrahim
  • Premalatha Balachandran
  • Jin Zhang
  • Samir A. RossEmail author
Original Research
  • 44 Downloads

Abstract

A new yohimbine type alkaloid N-methylarcinine (1), and the known alkaloid, holeinine (2), have been isolated from the methanolic leaf extract of Ochrosia elliptica grown in Egypt. The structures of the isolated metabolites were elucidated via 1D and 2D NMR data, as well as HRESIMS spectra and the spectral data were compared with the existing data available from literature. These two alkaloids are very different in activity from previously reported class type alkaloids, where they showed weak cytotoxic activity against K-562 leukemia cells while other compounds from this class were highly toxic in nature. Interestingly, holeinine (2) showed unique induction of FOXO expression, a cancer signaling pathway. FOXO is involved in the expression of death receptor ligands, such as TNF apoptosis ligand, where its activation plays a critical role in tumor suppression. As several anticancer leads targeting FOXO signaling gain more attention, this compound could be a candidate for drug development after the determination of its therapeutic efficacy and more mechanistic studies need to be evaluated.

Keywords

Ochrosia elliptica Apocynaceae Yohimbine alkaloid Holeinine FOXO 

Notes

Acknowledgements

This work is partially supported by the USDA ARS Specific Cooperative Agreement No. 58-6408-2-00.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2019_2399_MOESM1_ESM.docx (7.4 mb)
Supplementary Information

References

  1. Carroll AR, Addepalli R, Fechner G, Smith J, Guymer GP, Forster PI, Quinn RJ (2008) Alkaloids from the Australian rainforest tree Ochrosia moorei. J Nat Prod 71(6):1063–1065CrossRefGoogle Scholar
  2. Chen AH, Liu QL, Ma YL, Jiang ZH, Tang JY, Liu YP, Chen GY, Fu YH, Xu W (2017) A new monoterpenoid indole alkaloid from Ochrosia elliptica. Nat Prod Res 31(13):1490–1494CrossRefGoogle Scholar
  3. El-shiekh RA, Al-Mahdy DA, Hifnawy MS, Tzanova T, Evian-Bana E, Philippot S, Bagrel D, Abdelsattar EA (2017) Chemical and biological investigation of Ochrosia elliptica in Egypt. Rec Nat Prod 11(6):552–557CrossRefGoogle Scholar
  4. Greer EL, Brunet A (2005) Foxo transcription factors at the interface between longevity and tumor suppression. Oncogene 24:7410–7425CrossRefGoogle Scholar
  5. Hendrian (2004) Revision of Ochrosia (Apocynaceae) in Malesia. Blume - Biodivers, Evol Biogeogr Plants 49(1):101–128CrossRefGoogle Scholar
  6. Kageyama M, Li K, Sun S, Xing G, Gao R, Lei Z, Zhang Z (2018) Anti-tumor and anti-metastasis activities of honey bee larvae powder by suppressing the expression of EZH2. Biomed Pharm 105:690–696CrossRefGoogle Scholar
  7. Kim JY, Lee SG, Chung JY, Kim YJ, Park JE, Koh H, Han MS, Park YC, Yoo YH, Kim JM (2011) Ellipticine induces apoptosis in human endometrial cancer cells: the potential involvement of reactive oxygen species and mitogen-activated protein kinases. Toxicology 289(2–3):91–102CrossRefGoogle Scholar
  8. Kuo PL, Hsu YL, Chang CH, Lin CC (2005) The mechanism of ellipticine-induced apoptosis and cell cycle arrest in human breast MCF-7 cancer cells. Cancer Lett 223(2):293–301CrossRefGoogle Scholar
  9. Kuroda M, Mimaki Y, Kawase N, Yokosuka A, Sashida Y, Kagiya A (1999) Cytotoxic alkaloids from the barks of Ochrosia elliptica. Nat Med (Tokyo) 53(5):272Google Scholar
  10. Labib RM, Ebada SS, Youssef FS, Ashour ML, Ross SA (2016) Ursolic acid, a natural pentacylcic triterpene from Ochrosia elliptica and its role in the management of certain neglectedtropical diseases. Pharm Mag 12(48):319–325Google Scholar
  11. Lichota A, Gwozdzinski K (2018) Anticancer activity of natural compounds from plant and marine environment. Int J Mol Sci 19:3533CrossRefGoogle Scholar
  12. Liu Y, Wang X, Li X, Li K, Huang L, Wen C, Fu Y (2015) Studies on non-alkaloid constituents from Ochrosia elliptica. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China. J Chin Mater Med 40(8):1508–1513Google Scholar
  13. Farhan M, Wang H, Gaur U, Little PJ, Jiangping X, Zheng W (2017) Foxo signaling pathways as therapeutic targets incancer. IntJ Bio Sci 13:815–827CrossRefGoogle Scholar
  14. Sainsbury M, Webb B (1972) Minor alkaloids of Bleekeria vitiensis. Phytochem 11(7):2337–2339CrossRefGoogle Scholar
  15. Salim AA, Garson MJ, Craik DJ (2004) New indole alkaloids from the roots of Ochrosia acuminata. J Nat Prod 67(10):1719–1721CrossRefGoogle Scholar
  16. Stiborova M, Rupertova M, Frei E (2011) Cytochrome p 450- and peroxidase-mediated oxidation of anticancer alkaloid ellipticine dictates its anti-tumor efficiency. Biochim Biophys Acta 1814(1):175–185CrossRefGoogle Scholar
  17. Zaki MA, Balachandran P, Khan S, Wang M, Mohammed R, Hetta MH, Pasco DS, Muhammad I (2013) Cytotoxicity and modulation of cancer-related signaling by (Z)-and (E)-3,4,3′,5′-tetramethoxystilbene isolated from Eugenia rigida. J Nat Prod 76(4):679–684CrossRefGoogle Scholar
  18. Zhang H, Fang J, Yao D, Wu Y, Ip C, Dong Y (2010) Activation of foxo1 is critical for the anticancer effect of methylseleninic acid in prostate cancer cells. Prostate 70(12):1265–1273Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmacognosy, Faculty of PharmacyAin Shams UniversityCairoEgypt
  2. 2.National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of PharmacyUniversity of MississippiOxfordUSA
  3. 3.Department of Chemistry of Natural CompoundsNational Research CenterCairoEgypt
  4. 4.Department of BioMolecular Sciences, School of PharmacyUniversity of MississippiOxfordUSA

Personalised recommendations