FOXO signal activating alkaloids isolated from Ochrosia elliptica leaf cultivated in Egypt
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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.
KeywordsOchrosia elliptica Apocynaceae Yohimbine alkaloid Holeinine FOXO
This work is partially supported by the USDA ARS Specific Cooperative Agreement No. 58-6408-2-00.
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Conflict of interest
The authors declare that they have no conflict of interest.
- 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
- 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
- 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
- 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