cardenolides

Summary

Summary: C(23)-steroids with methyl groups at C-10 and C-13 and a five-membered lactone at C-17. They are aglycone constituents of CARDIAC GLYCOSIDES and must have at least one double bond in the molecule. The class includes cardadienolides and cardatrienolides. Members include DIGITOXIN and DIGOXIN and their derivatives and the STROPHANTHINS.

Top Publications

  1. Piacente S, Masullo M, De Neve N, Dewelle J, Hamed A, Kiss R, et al. Cardenolides from Pergularia tomentosa display cytotoxic activity resulting from their potent inhibition of Na+/K+-ATPase. J Nat Prod. 2009;72:1087-91 pubmed publisher
    ..The data revealed that these cardenolides displayed marked cytotoxic activity...
  2. Qazzaz H, Cao Z, Bolanowski D, Clark B, Valdes R. De novo biosynthesis and radiolabeling of mammalian digitalis-like factors. Clin Chem. 2004;50:612-20 pubmed
    Digoxin-like immunoreactive factors (DLIFs) are endogenous mammalian cardenolides with structural features similar to those of the plant-derived digitalis compounds...
  3. Jiang M, Dai Y, Gao H, Zhang X, Wang G, He J, et al. Cardenolides from Antiaris toxicaria as potent selective Nur77 modulators. Chem Pharm Bull (Tokyo). 2008;56:1005-8 pubmed
    ..Inhibition of cancer cell growth was accompanied with induction of the expression of Nur77, a potent apoptotic member of the steroid/thyroid hormone receptor superfamily. ..
  4. Li J, Qing C, Chen C, Hao X, Liu H. Cytotoxicity of cardenolides and cardenolide glycosides from Asclepias curassavica. Bioorg Med Chem Lett. 2009;19:1956-9 pubmed publisher
    ..02 microM against the two cancer cell lines and the new compound 13 had significant cytotoxic activity with IC(50) values of 0.69 and 1.46 microM, respectively. ..
  5. Zhao M, Bai L, Wang L, Toki A, Hasegawa T, Kikuchi M, et al. Bioactive cardenolides from the stems and twigs of Nerium oleander. J Nat Prod. 2007;70:1098-103 pubmed
    Four new cardenolide monoglycosides, cardenolides N-1 (1), N-2 (2), N-3 (3), and N-4 (4), were isolated from Nerium oleander, together with two known cardenolides, 5 and 12, and seven cardenolide monoglycosides, 6-11 and 13...
  6. Berendes E, Cullen P, Van Aken H, Zidek W, Erren M, Hübschen M, et al. Endogenous glycosides in critically ill patients. Crit Care Med. 2003;31:1331-7 pubmed
    ..DLIS but not endogenous ouabain concentrations were found to be related to left ventricular function. ..
  7. Florkiewicz R, Anchin J, Baird A. The inhibition of fibroblast growth factor-2 export by cardenolides implies a novel function for the catalytic subunit of Na+,K+-ATPase. J Biol Chem. 1998;273:544-51 pubmed
    ..In an attempt to better understand this process, we have identified a family of related compounds, "cardenolides," that inhibit FGF-2 export...
  8. Dobler S, Petschenka G, Pankoke H. Coping with toxic plant compounds--the insect's perspective on iridoid glycosides and cardenolides. Phytochemistry. 2011;72:1593-604 pubmed publisher
    ..In this review, we focus on two compound classes, iridoid glycosides and cardenolides, which can be found in the food plants of a large number of insect species that display various degrees of ..
  9. Al Ghoul M, Valdes R. Mammalian cardenolides in cancer prevention and therapeutics. Ther Drug Monit. 2008;30:234-8 pubmed publisher

More Information

Publications62

  1. Bai L, Zhao M, Toki A, Sakai J, Yang X, Bai Y, et al. Three new cardenolides from methanol extract of stems and twigs of Nerium oleander. Chem Pharm Bull (Tokyo). 2010;58:1088-92 pubmed
    Two new cardenolide monoglycosides, cardenolides B-1 (1) and B-2 (2) were isolated from Nerium oleander, together with oleagenin (3) which is the first isolated compound from natural sources...
  2. Rasmann S, Agrawal A. Latitudinal patterns in plant defense: evolution of cardenolides, their toxicity and induction following herbivory. Ecol Lett. 2011;14:476-83 pubmed publisher
    ..we show that variation among plant species in the induction of toxic cardenolides is explained by latitude, with higher inducibility evolving more frequently at lower latitudes...
  3. Dasgupta A. Endogenous and exogenous digoxin-like immunoreactive substances: impact on therapeutic drug monitoring of digoxin. Am J Clin Pathol. 2002;118:132-40 pubmed
    ..Therefore, interference of both endogenous and exogenous DLISs in serum digoxin measurement can be eliminated by monitoring digoxin concentrations in the protein-free ultrafiltrates. ..
  4. Rasmann S, Agrawal A, Cook S, Erwin A. Cardenolides, induced responses, and interactions between above- and belowground herbivores of milkweed (Asclepias spp.). Ecology. 2009;90:2393-404 pubmed
    ..Milkweeds in the genus Asclepias are a classic chemically defended clade of plants with toxic cardenolides (cardiac glycosides) and pressurized latex employed as anti-herbivore weapons...
  5. Mildenberger E, Oels K, Bauer K, Paul M, Versmold H. Digoxin-like immunoreactive substance in nonoliguric hyperkalemia of the premature infant. Biol Neonate. 2003;83:182-7 pubmed
    ..24, p < 0.002). 24 h after birth there was no correlation between [DLIS] and [K+]. Thus, a major role of DLIS in nonoliguric hyperkalemia could not be established. ..
  6. Dobler S, Dalla S, Wagschal V, Agrawal A. Community-wide convergent evolution in insect adaptation to toxic cardenolides by substitutions in the Na,K-ATPase. Proc Natl Acad Sci U S A. 2012;109:13040-5 pubmed publisher
    ..Target site insensitivity to cardenolides is a prime candidate for studying molecular convergence because herbivores in six orders of insects have ..
  7. Lhinhatrakool T, Sutthivaiyakit S. 19-Nor- and 18,20-epoxy-cardenolides from the leaves of Calotropis gigantea. J Nat Prod. 2006;69:1249-51 pubmed
    Two new cardenolides (1 and 2) along with 12 known compounds were isolated from the dichloromethane extract of the leaves of Calotropis gigantea. The structural elucidation was accomplished by spectroscopic methods...
  8. Cao S, Brodie P, Miller J, Ratovoson F, Callmander M, Randrianasolo S, et al. Antiproliferative cardenolides of an Elaeodendron sp. from the Madagascar rain forest(1). J Nat Prod. 2007;70:1064-7 pubmed
    ..led to the isolation of two new cardenolides, elaeodendrosides T and U (1 and 2)...
  9. Schoner W, Scheiner Bobis G. Endogenous and exogenous cardiac glycosides and their mechanisms of action. Am J Cardiovasc Drugs. 2007;7:173-89 pubmed
    ..It lowers BP in ouabain- and adducin-dependent hypertension in rats and is a promising new class of antihypertensive medication in humans. ..
  10. Wang T, Hojo T, Ran F, Wang R, Wang R, Chen H, et al. Cardenolides from Saussurea stella with cytotoxicity toward cancer cells. J Nat Prod. 2007;70:1429-33 pubmed
    Three new cardenolides, 3-O-beta-D-fucopyranosylstrophanthidin (1), 3-O-beta-D-quinovopyranosylperiplogenin (2), and 3-O-beta-D-glucopyranosyl-(1 --> 4)-alpha- l-rhamnopyranosylcannogenin (3), together with seven known cardenolides (4- ..
  11. Seeka C, Sutthivaiyakit S. Cytotoxic cardenolides from the leaves of Calotropis gigantea. Chem Pharm Bull (Tokyo). 2010;58:725-8 pubmed
    ..The isolated compounds were evaluated for their inhibitory activities against a panel of cell lines. ..
  12. Antczak C, Kloepping C, Radu C, Genski T, Müller Kuhrt L, Siems K, et al. Revisiting old drugs as novel agents for retinoblastoma: in vitro and in vivo antitumor activity of cardenolides. Invest Ophthalmol Vis Sci. 2009;50:3065-73 pubmed publisher
    ..It allows local delivery of relatively high doses of chemotherapy agents while bypassing general blood circulation. For this reason, this study was undertaken to revisit some of the FDA-approved drugs for the treatment of retinoblastoma...
  13. Rashan L, Franke K, Khine M, Kelter G, Fiebig H, Neumann J, et al. Characterization of the anticancer properties of monoglycosidic cardenolides isolated from Nerium oleander and Streptocaulon tomentosum. J Ethnopharmacol. 2011;134:781-8 pubmed publisher
    For identification of the active constituents we investigated the anticancer activity of cardenolides from Streptocaulon tomentosum Wight & Arn. (Asclepiadaceae) and from Nerium oleander L...
  14. Pádua R, Waibel R, Kuate S, Schebitz P, Hahn S, Gmeiner P, et al. A simple chemical method for synthesizing malonyl hemiesters of 21-hydroxypregnanes, potential intermediates in cardenolide biosynthesis. Steroids. 2008;73:458-65 pubmed publisher
    ..The malonylation protocol was optimized using deoxycorticosterone (DOC) as the pregnane educt. ..
  15. Petschenka G, Fandrich S, Sander N, Wagschal V, Boppre M, Dobler S. Stepwise evolution of resistance to toxic cardenolides via genetic substitutions in the Na+/K+ -ATPase of milkweed butterflies (lepidoptera: Danaini). Evolution. 2013;67:2753-61 pubmed publisher
    ..Unlike most other animal species, monarchs are largely insensitive to cardenolides, because their target site, the sodium pump (Na(+)/K(+) -ATPase), has evolved amino acid substitutions that ..
  16. Balzan S, Nicolini G, Iervasi A, Di Cecco P, Fommei E. Endogenous ouabain and acute salt loading in low-renin hypertension. Am J Hypertens. 2005;18:906-9 pubmed
    ..Our results do not support the hypothesis that EO is stimulated in low-renin hypertension by acute salt-volume expansion. ACTH could be a factor modulating EO secretion in this condition. ..
  17. Herl V, Fischer G, Müller Uri F, Kreis W. Molecular cloning and heterologous expression of progesterone 5beta-reductase from Digitalis lanata Ehrh. Phytochemistry. 2006;67:225-31 pubmed
    ..lanata was determined by Southern blot analysis. The 5beta-POR is highly conserved within the genus Digitalis and the respective genes and proteins share considerable homology to putative progesterone reductases from other plant species...
  18. Wen Y, Li X. [Recent advances in the function of Na+/K(+)-ATPase in signal transduction]. Sheng Li Ke Xue Jin Zhan. 2005;36:159-62 pubmed
  19. Datta P, Dasgupta A. Interference of endogenous digoxin-like immunoreactive factors in serum digoxin measurement is minimized in a new turbidimetric digoxin immunoassay on ADVIA 1650 analyzer. Ther Drug Monit. 2004;26:85-9 pubmed
    ..In contrast, we observed a good agreement between the target and observed concentrations when the new turbidimetric assay was used. We conclude that DLIF has minimal effect on serum digoxin measurements by the new turbidimetric assay. ..
  20. Pérez Bermúdez P, García A, Tuñón I, Gavidia I. Digitalis purpurea P5 beta R2, encoding steroid 5 beta-reductase, is a novel defense-related gene involved in cardenolide biosynthesis. New Phytol. 2010;185:687-700 pubmed publisher
    ..The correlation between P5 beta R2 expression and cardenolide formation demonstrates the key role of this gene in cardenolide biosynthesis, and therefore in the chemical defense of foxglove plants...
  21. Matsukawa M, Mukai T, Akizawa T, Miyatake S, Yoshioka M, Morris J, et al. Isolation and characterization of novel endogenous digitalis-like factors in the ovary of the giant toad, Bufo marinus. J Nat Prod. 1998;61:1476-81 pubmed
    ..The function of these three conjugates is not known but they are, like bufotoxins, potent inhibitors of Na+, K+-ATPase and may play a developmental role in the differentiation of toad oocytes...
  22. Gasper R, Mijatovic T, Bénard A, Derenne A, Kiss R, Goormaghtigh E. FTIR spectral signature of the effect of cardiotonic steroids with antitumoral properties on a prostate cancer cell line. Biochim Biophys Acta. 2010;1802:1087-94 pubmed publisher
  23. Cusi D. The strange behaviour of digitalis-like substances. J Hypertens. 2002;20:1075-7 pubmed
  24. Yadava R, Rathore K. A new cardenolide from the seeds of Terminalia bellerica. Fitoterapia. 2001;72:310-2 pubmed
    ..A new cardenolide, cannogenol 3-O-beta-D-galactopyranosyl-(1-->4)-O-alpha-L-rhamnopyranoside (1), was isolated form the seeds of Teminalia bellerica. ..
  25. Takada Y, Matsuo K, Ogura H, Bai L, Toki A, Wang L, et al. Odoroside A and ouabain inhibit Na+/K+-ATPase and prevent NF-kappaB-inducible protein expression by blocking Na+-dependent amino acid transport. Biochem Pharmacol. 2009;78:1157-66 pubmed publisher
    ..These results clearly demonstrate that odoroside A and ouabain prevent NF-kappaB-inducible protein expression by blocking the Na(+)-dependent amino acid transport. ..
  26. Miyagawa T, Ohtsuki T, Koyano T, Kowithayakorn T, Ishibashi M. Cardenolide glycosides of Thevetia peruviana and triterpenoid saponins of Sapindus emarginatus as TRAIL resistance-overcoming compounds. J Nat Prod. 2009;72:1507-11 pubmed publisher
    ..In addition, 1H and 13C NMR characterizations are shown for thevefolin (2) for the first time...
  27. Pan L, Zhang Y, Zhao W, Zhou X, Wang C, Deng F. The cardiac glycoside oleandrin induces apoptosis in human colon cancer cells via the mitochondrial pathway. Cancer Chemother Pharmacol. 2017;80:91-100 pubmed publisher
    ..The present results suggest that oleandrin induces apoptosis in human colorectal cancer cells via the mitochondrial pathway. Our findings provide new insight into the mechanism of anti-cancer property of oleandrin. ..
  28. Rogers J, Mikkilineni S, Cantuti Castelvetri I, Smith D, Huang X, Bandyopadhyay S, et al. The alpha-synuclein 5'untranslated region targeted translation blockers: anti-alpha synuclein efficacy of cardiac glycosides and Posiphen. J Neural Transm (Vienna). 2011;118:493-507 pubmed publisher
    ..These are candidate drugs with the potential to limit toxic SNCA expression in the brains of PD patients and animal models in vivo. ..
  29. Dinan L, Bourne P, Meng Y, Sarker S, Tolentino R, Whiting P. Assessment of natural products in the Drosophila melanogaster B(II) cell bioassay for ecdysteroid agonist and antagonist activities. Cell Mol Life Sci. 2001;58:321-42 pubmed
    ..Possible reasons for the prevalence of antagonists and for the low potency of the majority of them are discussed. ..
  30. Barrueto F, Kirrane B, Cotter B, Hoffman R, Nelson L. Cardioactive steroid poisoning: a comparison of plant- and animal-derived compounds. J Med Toxicol. 2006;2:152-5 pubmed
    ..by the type of lactone at carbon 17 (C17) of the steroid backbone: those with 5-membered lactone rings, or cardenolides, are derived mostly from plants with 6-membered rings or from animals with bufadienolides...
  31. Chapdelaine D, Belzile J, Deslongchamps P. A convergent synthesis of the cardenolide skeleton: intramolecular aldol condensation via reduction of alpha-bromoketones. J Org Chem. 2002;67:5669-72 pubmed
    ..The highly functionalized tetracyclic compound 52 is an important synthetic intermediate that is potentially amenable to natural cardenolide total synthesis. ..
  32. Shi H, Lindemann P. Expression of recombinant Digitalis lanata EHRH. cardenolide 16'-O-glucohydrolase in Cucumis sativus L. hairy roots. Plant Cell Rep. 2006;25:1193-8 pubmed
    ..Therefore, the cgh I transformed cucumber hairy roots may provide a valuable model for biotransformation of natural compounds by recombinant enzymes. ..
  33. Heise H, Vorwerk P, Fritsche K, Richter R. [Digoxin-like immunoreactivity in newborn infants--a pitfall of digoxin therapy?]. Kinderarztl Prax. 1993;61:108-11 pubmed
    ..9 ng/ml. We found a significant indirect correlation (rs = -0.34; p = 0.05) between age and serum DLIS concentration. A case report demonstrates the possibility of DLIS interference on digoxin drug monitoring. ..
  34. Chantrapromma S, Usman A, Fun H, Laphookhieo S, Karalai C, Rat a pa Y, et al. Bis[14beta-hydroxy-3beta-O-(L-thevetosyl)-5beta-card-20(22)-enolide] methanol solvate monohydrate and 3beta-O-(L-2'-o-acetylthevetosyl)-14beta-hydroxy-5beta-card-20(22)-enolide. Acta Crystallogr C. 2003;59:o68-70 pubmed
    ..O hydrogen bonds. In the packing of (II), the molecules are packed into columns by one O-H...O hydrogen bond, and are further interconnected into a three-dimensional network by one O-H...O and three C-H...O interactions. ..
  35. Afaq F, Saleem M, Aziz M, Mukhtar H. Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion markers in CD-1 mouse skin by oleandrin. Toxicol Appl Pharmacol. 2004;195:361-9 pubmed
    ..One might envision the use of chemopreventive agents such as oleandrin in an emollient or patch for chemoprevention or treatment of skin cancer. ..
  36. Puschett J. Marinobufagenin predicts and resibufogenin prevents preeclampsia: a review of the evidence. Am J Perinatol. 2012;29:777-85 pubmed publisher
    ..Expanded human trials of MBG as a predictor of the later development of PE are warranted as are studies of the efficacy and safety of RBG as a preventative/therapy. ..
  37. Couture J, Serbin S, Townsend P. Spectroscopic sensitivity of real-time, rapidly induced phytochemical change in response to damage. New Phytol. 2013;198:311-9 pubmed publisher
    ..Here, we used reflectance spectroscopy to characterize the foliar induction profile of cardenolides in Asclepias syriaca in response to damage, tracked in vivo changes and examined the influence of multiple ..
  38. Kumar A, Kurup P. Familial hypodigoxinemic membrane Na(+)-K(+) ATPase upregulatory syndrome - relation between digoxin status and cerebral dominance. Neurol India. 2002;50:340-7 pubmed
    ..The same biochemical patterns were observed in left hemispheric dominance as opposed to right hemispheric dominance. The significance of these findings in the pathogenesis of these disorders is discussed. ..
  39. Mijatovic T, Kiss R. Cardiotonic steroids-mediated Na+/K+-ATPase targeting could circumvent various chemoresistance pathways. Planta Med. 2013;79:189-98 pubmed publisher
    ..The aims of this review are to examine the various molecular pathways by which the NaK targeting can be more deleterious to biologically aggressive cancer cells than to normal cells. ..
  40. Tiwari S, Singh A. Toxic and sub-lethal effects of oleandrin on biochemical parameters of fresh water air breathing murrel, Channa punctatus (Bloch.). Indian J Exp Biol. 2004;42:413-8 pubmed
    ..It supports the view that the oleandrin is safer and may be useful substitute of other piscicides for removing the unwanted freshwater fishes from aquaculture ponds. ..
  41. Zhang L, Xu L, Yang S. Two new cardenolides from the roots of Streptocaulon griffithii. J Asian Nat Prod Res. 2006;8:613-7 pubmed
    Two new cardenolides, 3beta,5beta,14beta-trihydroxyl-card-16,20(22)-dienolide (1) and 3-O-beta-D-glucopyranosyl-5beta,14beta-dihydroxyl-card-16,20(22)-dienolide (2), together with seven known compounds identified as digitogenin (3), 16-O-..
  42. Mijatovic T, De Neve N, Gailly P, Mathieu V, Haibe Kains B, Bontempi G, et al. Nucleolus and c-Myc: potential targets of cardenolide-mediated antitumor activity. Mol Cancer Ther. 2008;7:1285-96 pubmed publisher
    The use of cardenolides like ouabain, digitoxin, or oleandrin has been reported previously many times as a means of potentially combating human refractory prostate cancer by inducing apoptosis through an increase in intracellular calcium ..
  43. Nicholls M, Lewis L, Yandle T, Lord G, McKinnon W, Hilton P. Ouabain, a circulating hormone secreted by the adrenals, is pivotal in cardiovascular disease. Fact or fantasy?. J Hypertens. 2009;27:3-8 pubmed publisher
    ..We submit that the position of ouabain as an endogenous, adrenally produced regulator of the sodium pump is of such importance that the current evidence needs either to put on a more secure footing or to lose its current status. ..
  44. Fedorova O, French A, Anderson D. Inhibition of erythrocyte Na,K-ATPase activity during anticipatory hypoventilation in micropigs. Am J Hypertens. 1996;9:1126-31 pubmed
  45. Graves S, Lincoln K, Cook S, Seely E. Digitalis-like factor and digoxin-like immunoreactive factor in diabetic women with preeclampsia, transient hypertension of pregnancy, and normotensive pregnancy. Am J Hypertens. 1995;8:5-11 pubmed
    ..non-IDDM NL BP: 3.3 +/- 0.6 v IDDM NL BP: 8.8 +/- 1.2% inhibition [Na,K]-ATPase, P = .0008; DLIF. non-IDDM NL BP: 0.22 +/- 0.02 v IDDM NL BP: 0.31 +/- 0.02 ng digoxin equivalents/mL, P = .005).(ABSTRACT TRUNCATED AT 250 WORDS) ..
  46. Goto A, Yamada K. Ouabain-like factor. Curr Opin Nephrol Hypertens. 1998;7:189-96 pubmed
    ..Several important questions remain, however, before it can be concluded that ouabain-like factor is indeed involved in the regulation of sodium homeostasis and blood pressure. ..
  47. Maillaud C, Lefebvre S, Sebat C, Barguil Y, Cabalion P, Cheze M, et al. Double lethal coconut crab (Birgus latro L.) poisoning. Toxicon. 2010;55:81-6 pubmed publisher
    ..human poisoning with the kernel of fruits of trees belonging to the genus Cerbera, known to contain cardiotoxic cardenolides, appear to be very similar to our cases...
  48. Warashina T, Shikata K, Miyase T, Fujii S, Noro T. New cardenolide and acylated lignan glycosides from the aerial parts of Asclepias curassavica. Chem Pharm Bull (Tokyo). 2008;56:1159-63 pubmed
    ..Asclepiadaceae). The structure of each compound was determined based on interpretations of NMR and MS measurements and chemical evidence. ..
  49. Agrawal A, Petschenka G, Bingham R, Weber M, Rasmann S. Toxic cardenolides: chemical ecology and coevolution of specialized plant-herbivore interactions. New Phytol. 2012;194:28-45 pubmed publisher
    b>Cardenolides are remarkable steroidal toxins that have become model systems, critical in the development of theories for chemical ecology and coevolution...
  50. Datté J, Ziegler A. Pharmacological investigation on nigrescigenin-a cardenolide from Parquetina nigrescens (Afzel.) Bullock: comparative studies on cardiotonic effects of Parquetina nigrescens, g-strophanthin and noradrenaline in guinea-pig isolated atria. J Pharm Pharmacol. 2001;53:859-66 pubmed
    ..nigrescens extract but also by the cardenolides known to be present in P. nigrescens.
  51. Nasu S, Milas L, Kawabe S, Raju U, Newman R. Enhancement of radiotherapy by oleandrin is a caspase-3 dependent process. Cancer Lett. 2002;185:145-51 pubmed
    ..Inhibition of caspase-3 activation with Z-DEVD-FMK abrogated the oleandrin-induced enhancement of radiation response suggesting that both oleandrin and radiation share a caspase-3 dependent mechanism of apoptosis in the PC-3 cell line. ..
  52. Wang J, Staessen J, Messaggio E, Nawrot T, Fagard R, Hamlyn J, et al. Salt, endogenous ouabain and blood pressure interactions in the general population. J Hypertens. 2003;21:1475-81 pubmed
    ..Plasma ouabain behaves as a blood pressure modulating factor, possibly released in response to potassium, either inhibiting the pressor effect of an excessive salt intake or counteracting the depressor action of sodium depletion. ..