Allen DG, Eisner DA, Wray SC (1985) Birthday present for digitalis. Nature 316:674–675. https://doi.org/10.1038/316674a0

Article  CAS  PubMed  Google Scholar 

Askari A (2019) The sodium pump and digitalis drugs: dogmas and fallacies. Pharmacol Res Perspect 7:e00505. https://doi.org/10.1002/prp2.505

Article  PubMed  PubMed Central  Google Scholar 

Bai L, Wang L, Zhao M, Toki A, Hasegawa T, Ogura H, Kataoka T, Hirose K, Sakai J, Bai J, Ando M (2007) Bioactive pregnanes from Nerium oleander. J Nat Prod 70:14–18. https://doi.org/10.1021/np068030o

Article  CAS  PubMed  Google Scholar 

Begum S, Siddiqui BS, Sultana R, Zia A, Suria A (1999) Bio-active cardenolides from the leaves of Nerium oleander. Phytochemistry 50:435–438. https://doi.org/10.1016/s0031-9422(98)00523-8

Article  CAS  PubMed  Google Scholar 

Chen YY, Wen SY, Deng CM, Yin XF, Sun ZH, Jiang MM, He QY (2019) Proteomic analysis reveals that odoroside A triggers G2/M arrest and apoptosis in colorectal carcinoma through ROS-p53 pathway. Proteomics 19:e1900092. https://doi.org/10.1002/pmic.201900092

Article  CAS  PubMed  Google Scholar 

Corbeil CR, Williams CI, Labute P (2012) Variability in docking success rates due to dataset preparation. J Comput Aid Mol Des 26:775–786. https://doi.org/10.1007/s10822-012-9570-1

Article  CAS  Google Scholar 

Cornelius F, Mahmmoud YA (2003) Themes in ion pump regulation. Ann NYAcad Sci 986:579–586. https://doi.org/10.1111/j.1749-6632.2003.tb07256.x

Article  CAS  Google Scholar 

Eichhorn EJ, Gheorghiade M (2022) Digoxin. Prog Cardiovasc Dis 44:251–266. https://doi.org/10.1053/pcad.2002.31591

Article  CAS  Google Scholar 

Fu L, Zhang S, Li N, Wang J, Zhao M, Sakai J, Hasegawa T, Mitsui T, Kataoka T, Oka S, Kiuchi M, Hirose K, Ando M (2005) Three new triterpenes from Nerium oleander and biological activity of the isolated compounds. J Nat Prod 68:198–206. https://doi.org/10.1021/np040072u

Article  CAS  PubMed  Google Scholar 

Gheorghiade M, van Veldhuisen DJ, Colucci WS (2006) Contemporary use of digoxin in the management of cardiovascular disorders. Circulation 113:2556–2564. https://doi.org/10.1161/circulationaha.105.560110

Article  PubMed  Google Scholar 

Hamlyn JM, Blaustein MP (2016) Endogenous ouabain: recent advances and controversies. Hypertension 68:526–532. https://doi.org/10.1161/HYPERTENSIONAHA.116.06599

Article  CAS  PubMed  Google Scholar 

Hamlyn JM, Blaustein MP, Bova S, DuCharme DW, Harris DW, Mandel F, Mathews WR, Ludens JH (1991) Identification and characterization of a ouabain-like compound from human plasma. Proc Natl Acad Sci USA 88:6259–6263. https://doi.org/10.1073/pnas.88.14.6259

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hu X, Chen T, Zhang S, Zhang Q, Li C, Wang X (2022) Antitumour effect of odoroside A and its derivative on human leukaemia cells through the ROS/JNK pathway. Basic Clin Pharmacol Toxicol 130:56–69. https://doi.org/10.1111/bcpt.13673

Article  CAS  PubMed  Google Scholar 

Kiran C, Prasad DN (2014) A review on: nerium oleander Linn. (Kaner). Int J Pharmacogn Phytochem Res 6:593–597

Google Scholar 

Ko YS, Rugira T, Jin H, Park SW, Kim HJ (2018) Oleandrin and its derivative Odoroside A, both cardiac glycosides, exhibit anticancer effects by inhibiting invasion via suppressing the STAT-3 signaling pathway. Int J Mol Sci 19:3350–3366. https://doi.org/10.3390/ijms19113350

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kometiani P, Liu L, Askari A (2005) Digitalis-induced signaling by Na+/K+-ATPase in human breast cancer cells. Mol Pharmacol 67:929–936. https://doi.org/10.1124/mol.104.007302

Article  CAS  PubMed  Google Scholar 

Laursen M, Yatime L, Nissen P, Fedosova NU (2013) Crystal structure of the high-affinity Na+K+-ATPase-ouabain complex with Mg2+ bound in the cation binding site. Proc Natl Acad Sci USA 110:10958–10963. https://doi.org/10.1073/pnas.1222308110

Article  PubMed  PubMed Central  Google Scholar 

Laursen M, Gregersen JL, Yatime L, Nissen P, Fedosova NU (2015) Structures and characterization of digoxin- and bufalin-bound Na+, K+-ATPase compared with the ouabain-bound complex. Proc Natl Acad Sci USA 112:1755–1760. https://doi.org/10.1073/pnas.1422997112

Article  CAS  PubMed  PubMed Central  Google Scholar 

Manna SK, Sah NK, Newman RA, Cisneros A, Aggarwal BB (2000) Oleandrin suppresses activation of nuclear transcription factor-kappaB, activator protein-1, and c-Jun NH2-terminal kinase. Cancer Res 60:3838–3847

CAS  PubMed  Google Scholar 

Manunta P, Ferrandi M, Bianchi G, Hamlyn JM (2009) Endogenous ouabain in cardiovascular function and disease. J Hypertens 27:9–18. https://doi.org/10.1097/HJH.0b013e32831cf2c6

Article  CAS  PubMed  Google Scholar 

Menger L, Vacchelli E, Adjemian S, Martins I, Ma Y, Shen S, Yamazaki T, Sukkurwala AQ, Michaud M, Mignot G, Schlemmer F, Sulpice E, Locher C, Gidrol X, Ghiringhelli F, Modjtahedi N, Galluzzi L, André F, Zitvogel L, Kepp O, Kroemer G (2012) Cardiac glycosides exert anticancer effects by inducing immunogenic cell death. Sci Transl Med 4:143ra99. https://doi.org/10.1126/scitranslmed.3003807

Article  CAS  PubMed  Google Scholar 

Nishioka T, Endo-Umeda K, Ito Y, Shimoda A, Takeuchi A, Tode C, Hirota Y, Osakabe N, Makishima M, Suhara Y (2019) Synthesis and in vitro evaluation of novel liver X receptor agonists based on naphthoquinone derivatives. Molecules 24:4316–4326. https://doi.org/10.3390/molecules24234316

Article  CAS  PubMed  PubMed Central  Google Scholar 

Okina Y, Takeuchi F, Yokomichi T, Takada Y, Kataoka T (2015) Cardenolide aglycones inhibit tumor necrosis factor α-induced expression of intercellular adhesion molecule-1 at the translation step by blocking Na+/K+-ATPase. Biological and Pharmaceutical Bulletin. 38(1):39–47

Article  CAS  PubMed  Google Scholar 

Paula S, Tabet MR, Ball WJ (2005) Interactions between cardiac glycosides and sodium/potassium-ATPase: three-dimensional structure-activity relationship models for ligand binding to the E2-Pi form of the enzyme versus activity inhibition. Biochemistry 44:498–510. https://doi.org/10.1021/bi048680w

Article  CAS  PubMed  Google Scholar 

Prassas I, Diamandis EP (2008) Novel therapeutic applications of cardiac glycosides. Nat Rev Drug Discov 7:926–935. https://doi.org/10.1038/nrd2682

Article  CAS  PubMed  Google Scholar 

Qiu LY, Koenderink JB, Swarts HG, Willems PH, De Pont JJ (2003) Phe783, Thr797, and Asp804 in transmembrane hairpin M5–M6 of Na+, K+-ATPase play a key role in ouabain binding. J Biol Chem 278:47240–47244. https://doi.org/10.1074/jbc.M308833200

Article  CAS  PubMed  Google Scholar 

Ren YP, Zhang MJ, Zhang T, Huang RW (2014) Dual effects of ouabain on the regulation of proliferation and apoptosis in human umbilical vein endothelial cells: involvement of Na(+)-K(+)-ATPase α-subunits and NF-κB. Int J Clin Exp Med 7:1214–1222

PubMed  PubMed Central  Google Scholar 

Rose AM, Valdes R (1994) Understanding the sodium pump and its relevance to disease. Clin Chem 40:1674–1685. https://doi.org/10.1093/clinchem/40.9.1674

Article  CAS  PubMed  Google Scholar 

Schoner W (2002) Endogenous cardiac glycosides, a new class of steroid hormones. Eur J Biochem 269:2440–2448. https://doi.org/10.1046/j.1432-1033.2002.02911.x

Article  CAS  PubMed  Google Scholar 

Schoner W, Scheiner-Bobis G (2007) Endogenous and exogenous cardiac glycosides: their roles in hypertension, salt metabolism, and cell growth. Am J Physiol Cell Physiol 293:C509–C536. https://doi.org/10.1152/ajpcell.00098.2007

Article  CAS  PubMed  Google Scholar 

Škubník J, Bejček J, Pavlíčková VS, Rimpelová S (2021) Repurposing cardiac glycosides: drugs for heart failure surmounting viruses. Molecules 26:5627–5646. https://doi.org/10.3390/molecules26185627

Article  CAS  PubMed  PubMed Central  Google Scholar 

Takada Y, Matsuo K, Ogura H, Bai L, Toki A, Wang L, Ando M, Kataoka T (2009) Odoroside A and ouabain inhibit Na+/K+-ATPase and prevent NF-kappaB-inducible protein expression by blocking Na+-dependent amino acid transport. Biochem Pharmacol 78:1157–1166. https://doi.org/10.1016/j.bcp.2009.06.027

Article  CAS  PubMed  Google Scholar 

Therien AG, Blostein R (2000) Mechanisms of sodium pump regulation. Am J Physiol Cell Physiol 279:C541–C566. https://doi.org/10.1152/ajpcell.2000.279.3.C541

Article  CAS  PubMed  Google Scholar 

Trott O, Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31:455–461. https://doi.org/10.1002/jcc.21334

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tu W, Qian S (2019) Anti-epileptic effect of 16-O-acetyldigitoxigenin via suppressing mTOR signaling pathway. Cell Mol Biol 65:59–63. https://doi.org/10.14715/cmb/2019.65.5.10

Article  PubMed  Google Scholar 

Van Quaquebeke E, Simon G, André A, Dewelle J, El Yazidi M, Bruyneel F, Tuti J, Nacoulma O, Guissou P, Decaestecker C, Braekman JC, Kiss R, Darro F (2005) Identification of a novel cardenolide (2′′-oxovoruscharin) from Calotropis procera and the hemisynthesis of novel derivatives displaying potent in vitro antitumor activities and high in vivo tolerance: structure-activity relationship analyses. J Med Chem 48:849–856. https://doi.org/10.1021/jm049405a