Cardiac Glycosides as Immune System Modulators

. 2021 Apr 29 ; 11 (5) : . [epub] 20210429

Jazyk angličtina Země Švýcarsko Médium electronic

Typ dokumentu časopisecké články, práce podpořená grantem, přehledy

Perzistentní odkaz   https://www.medvik.cz/link/pmid33947098

Cardiac glycosides (CGs) are natural steroid compounds occurring both in plants and animals. They are known for long as cardiotonic agents commonly used for various cardiac diseases due to inhibition of Na+/K+-ATPase (NKA) pumping activity and modulating heart muscle contractility. However, recent studies show that the portfolio of diseases potentially treatable with CGs is much broader. Currently, CGs are mostly studied as anticancer agents. Their antiproliferative properties are based on the induction of multiple signaling pathways in an NKA signalosome complex. In addition, they are strongly connected to immunogenic cell death, a complex mechanism of induction of anticancer immune response. Moreover, CGs exert various immunomodulatory effects, the foremost of which are connected with suppressing the activity of T-helper cells or modulating transcription of many immune response genes by inhibiting nuclear factor kappa B. The resulting modulations of cytokine and chemokine levels and changes in immune cell ratios could be potentially useful in treating sundry autoimmune and inflammatory diseases. This review aims to summarize current knowledge in the field of immunomodulatory properties of CGs and emphasize the large area of potential clinical use of these compounds.

Zobrazit více v PubMed

Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021 doi: 10.3322/caac.21660. PubMed DOI

Bejcek J., Spiwok V., Kmonickova E., Ruml T., Rimpelova S. Cardiac glycosides: On their therapeutic potential for cancer treatment. Chem. Listy. 2021;115:4–12.

Garcia I.J.P., de Oliveira G.C., Valadares J.M.D., Banfi F.F., Andrade S.N., Freitas T.R., Filho E.D.S.M., Santos H.D.L., Vieira G.M., Chaves M.H., et al. New bufadienolides extracted from Rhinella Marina inhibit Na,K-ATPase and induce apoptosis by activating caspases 3 and 9 in human breast and ovarian cancer cells. Steroids. 2019;152:108490. doi: 10.1016/j.steroids.2019.108490. PubMed DOI

Geng X., Wang F., Tian D., Huang L., Streator E., Zhu J., Kurihara H., He R., Yao X., Zhang Y., et al. Cardiac glycosides inhibit cancer through Na/K-ATPase-dependent cell death induction. Biochem. Pharmacol. 2020;182:114226. doi: 10.1016/j.bcp.2020.114226. PubMed DOI PMC

Kanwal N., Rasul A., Hussain G., Anwar H., Shah M.A., Sarfraz I., Riaz A., Batool R., Shahbaz M., Hussain A., et al. Oleandrin: A bioactive phytochemical and potential cancer killer via multiple cellular signaling pathways. Food Chem. Toxicol. 2020;143:111570. doi: 10.1016/j.fct.2020.111570. PubMed DOI

Lan Y.L., Zou Y.J., Lou J.C., Xing J.S., Wang X., Zou S., Ma B.B., Ding Y., Zhang B. The sodium pump α1 subunit regulates bufalin sensitivity of human glioblastoma cells through the p53 signaling pathway. Cell Biol. Toxicol. 2019;35:521–539. doi: 10.1007/s10565-019-09462-y. PubMed DOI

Leu W.J., Wang C.T., Hsu J.L., Chen I.S., Chang H.S., Guh J.H. Ascleposide, a natural cardenolide, induces anticancer signaling in human castration-resistant prostatic cancer through Na+/K+-ATPase internalization and tubulin acetylation. Prostate. 2020;80:305–318. doi: 10.1002/pros.23944. PubMed DOI

Michalak K., Rárová L., Kubala M., Štenclová T., Strnad M., Wicha J. Synthesis and evaluation of Na+/K+-ATP-ase inhibiting and cytotoxic in vitro activities of oleandrigenin and its selected 17 beta-(butenolidyl)-and 17 beta-(3-furyl)- analogues. Eur. J. Med. Chem. 2020;202:112520. doi: 10.1016/j.ejmech.2020.112520. PubMed DOI

Reddy D., Ghosh P., Kumavath R. Strophanthidin attenuates MAPK, PI3K/AKT/mTOR, and Wnt/beta-catenin signaling pathways in human cancers. Front. Oncol. 2020;9:1469. doi: 10.3389/fonc.2019.01469. PubMed DOI PMC

Reddy D., Kumavath R., Barh D., Azevedo V., Ghosh P. Anticancer and antiviral properties of cardiac glycosides: A review to explore the mechanism of actions. Molecules. 2020;25:3596. doi: 10.3390/molecules25163596. PubMed DOI PMC

Reddy D., Kumavath R., Tan T.Z., Ampasala D.R., Kumar A.P. Peruvoside targets apoptosis and autophagy through MAPK Wnt/beta-catenin and PI3K/AKT/mTOR signaling pathways in human cancers. Life Sci. 2020;241:117147. doi: 10.1016/j.lfs.2019.117147. PubMed DOI

Ren Y., Ribas H.T., Heath K., Wu S., Ren J., Shriwas P., Chen X., Johnson M.E., Cheng X., Burdette J.E., et al. Na+/K+-ATPase-targeted cytotoxicity of (+)-digoxin and several semisynthetic derivatives. J. Nat. Prod. 2020;83:638–648. doi: 10.1021/acs.jnatprod.9b01060. PubMed DOI PMC

Rimpelová S., Zimmermann T., Drašar P.B., Dolenský B., Bejček J., Kmoníčková E., Cihlářová P., Gurská S., Kuklíková L., Hajdůch M., et al. Steroid glycosides hyrcanoside and deglucohyrcanoside: On isolation, structural identification, and anticancer activity. Foods. 2021;10:136. doi: 10.3390/foods10010136. PubMed DOI PMC

Schneider N.F.Z., Menegaz D., Dagostin A.L.A., Persich L., Rocha S.C., Ramos A.C.P., Cortes V.F., Fontes C.F.L., de Pádua R.M., Munkert J., et al. Cytotoxicity of glucoevatromonoside alone and in combination with chemotherapy drugs and their effects on Na+,K+-ATPase and ion channels on lung cancer cells. Mol. Cell. Biochem. 2021;476:1825–1848. doi: 10.1007/s11010-020-04040-x. PubMed DOI

Song Y., Lee S.Y., Kim S., Choi I., Kim S.H., Shum D., Heo J., Kim A.R., Kim K.M., Seo H.R. Inhibitors of Na+/K+ ATPase exhibit antitumor effects on multicellular tumor spheroids of hepatocellular carcinoma. Sci. Rep. 2020;10:5318. doi: 10.1038/s41598-020-62134-4. PubMed DOI PMC

Sun X., Ng T.T.H., Sham K.W.Y., Zhang L., Chan M.T.V., Wu W.K.K., Cheng C.H.K. Bufalin, a traditional chinese medicine compound, prevents tumor formation in two murine models of colorectal cancer. Cancer Prev. Res. 2019;12:653–666. doi: 10.1158/1940-6207.CAPR-19-0134. PubMed DOI

Wang F., Liu L., Tong Y., Li L., Liu Y., Gao W.Q. Proscillaridin A slows the prostate cancer progression through triggering the activation of endoplasmic reticulum stress. Cell Cycle. 2020;19:541–550. doi: 10.1080/15384101.2020.1716484. PubMed DOI PMC

Wang Y., Ma Q., Zhang S., Liu H., Zhao B., Du B., Wang W., Lin P., Zhang Z., Zhong Y., et al. Digoxin enhances the anticancer effect on non-small cell lung cancer while reducing the cardiotoxicity of adriamycin. Front. Pharmacol. 2020;11:186. doi: 10.3389/fphar.2020.00186. PubMed DOI PMC

Bhusare B.P., John C.K., Bhatt V.P., Nikam T.D. In vitro propagation of Digitalis lanata Ehrh. through direct shoot regeneration—A source of cardiotonic glycosides. Ind. Crop Prod. 2018;121:313–319. doi: 10.1016/j.indcrop.2018.05.019. DOI

Curfman G. Digitalis glycosides for heart rate control in atrial fibrillation. JAMA. 2020;324:2508. doi: 10.1001/jama.2020.24578. PubMed DOI

Fujino T., Kuroda M., Matsuo Y., Kubo S., Tamura C., Sakamoto N., Mimaki Y., Hayakawa M. Cardenolide glycosides from the seeds of Digitalis purpurea exhibit carcinoma-specific cytotoxicity toward renal adenocarcinoma and hepatocellular carcinoma cells. Biosci. Biotechnol. Biochem. 2015;79:177–184. doi: 10.1080/09168451.2014.975183. PubMed DOI

Kirmizibekmez H., Masullo M., Festa M., Capasso A., Piacente S. Steroidal glycosides with antiproliferative activities from Digitalis trojana. Phytother. Res. 2014;28:534–538. doi: 10.1002/ptr.5012. PubMed DOI

Dunn D.E., He D.N., Yang P., Johansen M., Newman R.A., Lo D.C. In vitro and in vivo neuroprotective activity of the cardiac glycoside oleandrin from Nerium oleander in brain slice-based stroke models. J. Neurochem. 2011;119:805–814. doi: 10.1111/j.1471-4159.2011.07439.x. PubMed DOI

Balderas-López J.L., Barbonetti S., Pineda-Rosas E.L., Tavares-Carvalho J.C., Navarrete A. Cardiac glycosides from Cascabela thevetioides by HPLC-MS analysis. Rev. Bras. Farmacogn. 2019;29:441–444. doi: 10.1016/j.bjp.2019.04.008. DOI

Kohls S., Scholz-Böttcher B.M., Teske J., Zark P., Rullkötter J. Cardiac glycosides from yellow oleander (Thevetia peruviana) seeds. Phytochemistry. 2012;75:114–127. doi: 10.1016/j.phytochem.2011.11.019. PubMed DOI

Siddiqui B.S., Khatoon N., Begum S., Farooq A.D., Qamar K., Bhatti H.A., Ali S.K. Flavonoid and cardenolide glycosides and a pentacyclic triterpene from the leaves of Nerium oleander and evaluation of cytotoxicity. Phytochemistry. 2012;77:238–244. doi: 10.1016/j.phytochem.2012.01.001. PubMed DOI

Mohammadi S., French S.S., Neuman-Lee L.A., Durham S.L., Kojima Y., Mori A., Brodie E.D., Savitzky A.H. Corticosteroid responses of snakes to toxins from toads (bufadienolides) and plants (cardenolides) reflect differences in dietary specializations. Gen. Comp. Endocrinol. 2017;247:16–25. doi: 10.1016/j.ygcen.2017.03.015. PubMed DOI

Qi J., Zulfiker A.H.M., Li C., Good D., Wei M.Q. The Development of toad toxins as potential therapeutic agents. Toxins. 2018;10:336. doi: 10.3390/toxins10080336. PubMed DOI PMC

Buckalew V.M. Endogenous digitalis-like factors: An overview of the history. Front. Endocrinol. 2015;6:49. doi: 10.3389/fendo.2015.00049. PubMed DOI PMC

Buckalew V.M. Role of endogenous digitalis-like factors in the clinical manifestations of severe preeclampsia: A systematic review. Clin. Sci. 2018;132:1215–1242. doi: 10.1042/CS20171499. PubMed DOI

Melero C.P., Medarde M., San Feliciano A. A short review on cardiotonic steroids and their aminoguanidine analogues. Molecules. 2000;5:51–81. doi: 10.3390/50100051. DOI

Bejček J., Spiwok V., Kmoníčková E., Rimpelová S. Na+/K+-ATPase revisited: On its mechanism of action, role in cancer, and activity modulation. Molecules. 2021;26:1905. doi: 10.3390/molecules26071905. PubMed DOI PMC

Smith T.W. Digitalis. Mechanisms of action and clinical use. N. Engl. J. Med. 1988;318:358–365. doi: 10.1056/NEJM198802113180606. PubMed DOI

Kepp O., Menger L., Vacchelli E., Adjemian S., Martins I., Ma Y., Sukkurwala A.Q., Michaud M., Galluzzi L., Zitvogel L., et al. Anticancer activity of cardiac glycosides. Oncoimmunology. 2012;1:1640–1642. doi: 10.4161/onci.21684. PubMed DOI PMC

Paula S., Tabet M.R., Ball W.J. 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. 2005;44:498–510. doi: 10.1021/bi048680w. PubMed DOI

Lopina O.D., Tverskoi A.M., Klimanova E.A., Sidorenko S.V., Orlov S.N. Ouabain-induced cell death and survival. Role of α1-Na,K-ATPase-mediated signaling and [Na+]i/[K+]i-dependent gene expression. Front. Phys. 2020;11:1060. doi: 10.3389/fphys.2020.01060. PubMed DOI PMC

Pratt R.D., Brickman C.R., Cottrill C.L., Shapiro J.I., Liu J. The Na/K-ATPase Signaling: From specific ligands to general reactive oxygen species. Int. J. Mol. Sci. 2018;19:2600. doi: 10.3390/ijms19092600. PubMed DOI PMC

Cui X., Xie Z. Protein interaction and Na/K-ATPase-mediated signal transduction. Molecules. 2017;22:990. doi: 10.3390/molecules22060990. PubMed DOI PMC

Campia I., Gazzano E., Pescarmona G., Ghigo D., Bosia A., Riganti C. Digoxin and ouabain increase the synthesis of cholesterol in human liver cells. Cell. Mol. Life Sci. 2009;66:1580–1594. doi: 10.1007/s00018-009-9018-5. PubMed DOI PMC

Manna S.K., Sreenivasan Y., Sarkar A. Cardiac glycoside inhibits IL-8-induced biological responses by downregulating IL-8 receptors through altering membrane fluidity. J. Cell. Physiol. 2006;207:195–207. doi: 10.1002/jcp.20555. PubMed DOI

Katz A., Lifshitz Y., Bab-Dinitz E., Kapri-Pardes E., Goldshleger R., Tal D.M., Karlish S.J. Selectivity of digitalis glycosides for isoforms of human Na,K-ATPase. J. Biol. Chem. 2010;285:19582–19592. doi: 10.1074/jbc.M110.119248. PubMed DOI PMC

Wansapura A.N., Lasko V., Xie Z., Fedorova O.V., Bagrov A.Y., Lingrel J.B., Lorenz J.N. Marinobufagenin enhances cardiac contractility in mice with ouabain-sensitive alpha1 Na+-K+-ATPase. Am. J. Physiol. Heart Circ. Physiol. 2009;296:H1833–H1839. doi: 10.1152/ajpheart.00285.2009. PubMed DOI PMC

Liu L., Wu J., Kennedy D.J. Regulation of cardiac remodeling by cardiac Na+/K+-ATPase isoforms. Front. Physiol. 2016;7:382. doi: 10.3389/fphys.2016.00382. PubMed DOI PMC

Singh S.V., Fedorova O.V., Wei W., Rosen H., Horesh N., Ilani A., Lichtstein D. Na+, K+-ATPase α isoforms and endogenous cardiac steroids in prefrontal cortex of bipolar patients and controls. Int. J. Mol. Sci. 2020;21:5912. doi: 10.3390/ijms21165912. PubMed DOI PMC

Xie Z., Cai T. Na+-K+--ATPase-mediated signal transduction: From protein interaction to cellular function. Mol. Interv. 2003;3:157–168. doi: 10.1124/mi.3.3.157. PubMed DOI

Kutscher L.M., Shaham S. Non-apoptotic cell death in animal development. Cell Death Differ. 2017;24:1326–1336. doi: 10.1038/cdd.2017.20. PubMed DOI PMC

Gunawardena A.H.L.A.N. Programmed cell death and tissue remodelling in plants. J. Exp. Bot. 2008;59:445–451. doi: 10.1093/jxb/erm189. PubMed DOI

Allocati N., Masulli M., Di Ilio C., De Laurenzi V. Die for the community: An overview of programmed cell death in bacteria. Cell Death Dis. 2015;6:e1609. doi: 10.1038/cddis.2014.570. PubMed DOI PMC

Galluzzi L., Vitale I., Aaronson S.A., Abrams J.M., Adam D., Agostinis P., Alnemri E.S., Altucci L., Amelio I., Andrews D.W., et al. Molecular mechanisms of cell death: Recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ. 2018;25:486–541. doi: 10.1038/s41418-017-0012-4. PubMed DOI PMC

Galluzzi L., Vitale I., Warren S., Adjemian S., Agostinis P., Buque Martinez A., Chan T.A., Coukos G., Demaria S., Deutsch E., et al. Consensus guidelines for the definition, detection and interpretation of immunogenic cell death. J. Immunother. Cancer. 2020;8:e000337. doi: 10.1136/jitc-2019-000337. PubMed DOI PMC

Sun F., Cui L., Li T., Chen S., Song J., Li D. Oxaliplatin induces immunogenic cells death and enhances therapeutic efficacy of checkpoint inhibitor in a model of murine lung carcinoma. J. Recept. Signal. Transduct. Res. 2019;39:208–214. doi: 10.1080/10799893.2019.1655050. PubMed DOI

Kepp O., Zitvogel L., Kroemer G. Lurbinectedin: An FDA-approved inducer of immunogenic cell death for the treatment of small-cell lung cancer. Oncoimmunology. 2020;9:1795995. doi: 10.1080/2162402X.2020.1795995. PubMed DOI PMC

Du B., Waxman D.J. Medium dose intermittent cyclophosphamide induces immunogenic cell death and cancer cell autonomous type I interferon production in glioma models. Cancer Lett. 2020;470:170–180. doi: 10.1016/j.canlet.2019.11.025. PubMed DOI PMC

Panaretakis T., Kepp O., Brockmeier U., Tesniere A., Bjorklund A.C., Chapman D.C., Durchschlag M., Joza N., Pierron G., van Endert P., et al. Mechanisms of pre-apoptotic calreticulin exposure in immunogenic cell death. EMBO J. 2009;28:578–590. doi: 10.1038/emboj.2009.1. PubMed DOI PMC

Garg A.D., Dudek A.M., Ferreira G.B., Verfaillie T., Vandenabeele P., Krysko D.V., Mathieu C., Agostinis P. ROS-induced autophagy in cancer cells assists in evasion from determinants of immunogenic cell death. Autophagy. 2013;9:1292–1307. doi: 10.4161/auto.25399. PubMed DOI

Deng H., Yang W., Zhou Z., Tian R., Lin L., Ma Y., Song J., Chen X. Targeted scavenging of extracellular ROS relieves suppressive immunogenic cell death. Nat. Commun. 2020;11:4951. doi: 10.1038/s41467-020-18745-6. PubMed DOI PMC

Menger L., Vacchelli E., Adjemian S., Martins I., Ma Y., Shen S., Yamazaki T., Sukkurwala A.Q., Michaud M., Mignot G., et al. Cardiac glycosides exert anticancer effects by inducing immunogenic cell death. Sci. Transl. Med. 2012;4:143ra99. doi: 10.1126/scitranslmed.3003807. PubMed DOI

Xiang Y., Chen L., Li L., Huang Y. Restoration and enhancement of immunogenic cell death of cisplatin by coadministration with digoxin and conjugation to HPMA copolymer. ACS Appl. Mater. Interfaces. 2020;12:1606–1616. doi: 10.1021/acsami.9b19323. PubMed DOI

da Silva J.M.C., Campos M.L.A., Teixeira M.P., Faustino R.D.S., Aleixo R.C., Cavalcante F.J.P., Gomes L.R.O., de Albuquerque L.Z., Azevedo A.D.N., Cabral V.R., et al. Ouabain pre-treatment modulates B and T lymphocytes and improves survival of melanoma-bearing animals. Int. Immunopharmacol. 2020;86:106772. doi: 10.1016/j.intimp.2020.106772. PubMed DOI

Shih Y.L., Shang H.S., Chen Y.L., Hsueh S.C., Chou H.M., Lu H.F., Lee M.Z., Hou H.T., Chuang Y.Y., Lee M.H., et al. Ouabain promotes immune responses in WEHI-3 cells to generate leukemia mice through enhancing phagocytosis and natural killer cell activities in vivo. Environ. Toxicol. 2019;34:659–665. doi: 10.1002/tox.22732. PubMed DOI

Cavalcante-Silva L.H.A., Lima E.D., Carvalho D.C.M., de Sales-Neto J.M., Alves A.K.D.A., Galvao J.G.F.M., da Silva J.S.D.F., Rodrigues-Mascarenhas S. Much more than a cardiotonic steroid: Modulation of inflammation by ouabain. Front. Physiol. 2017;8:895. doi: 10.3389/fphys.2017.00895. PubMed DOI PMC

Shih Y.L., Chou J.S., Chen Y.L., Hsueh S.C., Chung H.Y., Lee M.H., Chen C.P., Lee M.Z., Hou H.T., Lu H.F., et al. Bufalin enhances immune responses in leukemic mice through enhancing phagocytosis of macrophage in vivo. In Vivo. 2018;32:1129–1136. doi: 10.21873/invivo.11355. PubMed DOI PMC

Yang Z., Tao Y., Xu X., Cai F., Yu Y., Ma L. Bufalin inhibits cell proliferation and migration of hepatocellular carcinoma cells via APOBEC3F induced intestinal immune network for IgA production signaling pathway. Biochem. Biophys. Res. Commun. 2018;503:2124–2131. doi: 10.1016/j.bbrc.2018.07.169. PubMed DOI

Xie S., Spelmink L., Codemo M., Subramanian K., Pütsep K., Henriques-Normark B., Olliver M. Cinobufagin modulates human innate immune responses and triggers antibacterial activity. PLoS ONE. 2016;11:e0160734. doi: 10.1371/journal.pone.0160734. PubMed DOI PMC

Cao Y., Song Y., An N., Zeng S., Wang D., Yu L., Zhu T., Zhang T., Cui J., Zhou C., et al. The effects of telocinobufagin isolated from Chan Su on the activation and cytokine secretion of immunocytes in vitro. Fundam. Clin. Pharmacol. 2009;23:457–464. doi: 10.1111/j.1472-8206.2009.00696.x. PubMed DOI

Yuan B., He J., Kisoh K., Hayashi H., Tanaka S., Si N., Zhao H.Y., Hirano T., Bian B., Takagi N. Effects of active bufadienolide compounds on human cancer cells and CD4+CD25+Foxp3+ regulatory T cells in mitogen-activated human peripheral blood mononuclear cells. Oncol. Rep. 2016;36:1377–1384. doi: 10.3892/or.2016.4946. PubMed DOI

Huh J.R., Leung M.W.L., Huang P., Ryan D.A., Krout M.R., Malapaka R.R.V., Chow J., Manel N., Ciofani M., Kim S.V., et al. Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity. Nature. 2011;472:486–490. doi: 10.1038/nature09978. PubMed DOI PMC

Karaś K., Sałkowska A., Walczak-Drzewiecka A., Ryba K., Dastych J., Bachorz R.A., Ratajewski M. The cardenolides strophanthidin, digoxigenin and dihydroouabain act as activators of the human ROR gamma/ROR gamma T receptors. Toxicol. Lett. 2018;295:314–324. doi: 10.1016/j.toxlet.2018.07.002. PubMed DOI

Karaś K., Sałkowska A., Sobalska-Kwapis M., Walczak-Drzewiecka A., Strapagiel D., Dastych J., Bachorz R.A., Ratajewski M. Digoxin, an overlooked agonist of RORγ/RORγT. Front. Pharmacol. 2018;9:1460. doi: 10.3389/fphar.2018.01460. PubMed DOI PMC

Wei Z., Wang Y., Zhang K., Liao Y., Ye P., Wu J., Wang Y., Li F., Yao Y., Zhou Y., et al. Inhibiting the Th17/IL-17A-related inflammatory responses with digoxin confers protection against experimental abdominal aortic aneurysm. Arterioscler. Thromb. Vasc. Biol. 2014;34:2429–2438. doi: 10.1161/ATVBAHA.114.304435. PubMed DOI

Calderón-Montaño J.M., Burgos-Morón E., López-Lázaro M. The in vivo antitumor activity of cardiac glycosides in mice xenografted with human cancer cells is probably an experimental artifact. Oncogene. 2014;33:2947–2948. doi: 10.1038/onc.2013.229. PubMed DOI

Tani S., Takano R., Tamura S., Oishi S., Iwaizumi M., Hamaya Y., Takagaki K., Nagata T., Seto S., Horii T., et al. Digoxin attenuates murine experimental colitis by downregulating Th17-related cytokines. Inflamm. Bowel. Dis. 2017;23:728–738. doi: 10.1097/MIB.0000000000001096. PubMed DOI

Saeed H., Mateen S., Moin S., Khan A.Q., Owais M. Cardiac glycoside digoxin ameliorates pro-inflammatory cytokines in PBMCs of rheumatoid arthritis patients in vitro. Int. Immunopharmacol. 2020;82:106331. doi: 10.1016/j.intimp.2020.106331. PubMed DOI

Shi H., Mao X., Zhong Y., Liu Y., Zhao X., Yu K., Zhu R., Wei Y., Zhu J., Sun H., et al. Digoxin reduces atherosclerosis in apolipoprotein E-deficient mice. Br. J. Pharmacol. 2016;173:1517–1528. doi: 10.1111/bph.13453. PubMed DOI PMC

Ouyang X., Han S.N., Zhang J.Y., Evangelos D., Nemeth B.T., Pacher P., Feng D., Bataller R., Cabezas J., Stärkel P., et al. Digoxin suppresses pyruvate kinase M2-promoted HIF-1α transactivation in steatohepatitis. Cell Metab. 2018;27:339–350.e3. doi: 10.1016/j.cmet.2018.01.007. PubMed DOI PMC

ClinicalTrials.gov. [(accessed on 14 March 2021)]; Available online: https://www.clinicaltrials.gov/ct2/show/NCT03559868?term=digoxin&recrs=abdf&draw=2&rank=7.

ClinicalTrials.gov. [(accessed on 14 March 2021)]; Available online: https://www.clinicaltrials.gov/ct2/show/NCT04216693?term=digoxin&recrs=abdf&draw=2&rank=6.

Zeitlin P.L., Diener-West M., Callahan K.A., Lee S., Talbot C.C., Pollard B., Boyle M.P., Lechtzin N. Digitoxin for airway inflammation in cystic fibrosis: Preliminary assessment of safety, pharmacokinetics, and dose Finding. Ann. Am. Thorac. Soc. 2017;14:220–229. doi: 10.1513/AnnalsATS.201608-649OC. PubMed DOI PMC

Zhakeer Z., Hadeer M., Tuerxun Z., Tuerxun K. Bufalin inhibits the inflammatory effects in asthmatic mice through the suppression of nuclear factor-kappa B activity. Pharmacology. 2017;99:179–187. doi: 10.1159/000450754. PubMed DOI

Galvão J.G.F.M., Cavalcante-Silva L.H.A., Carvalho D.C.M., Ferreira L.K.D.P., Monteiro T.M., Alves A.F., Ferreira L.A.M.P., Gadelha F.A.A.F., Piuvezam M.R., Rodrigues-Mascarenhas S. Ouabain attenuates ovalbumin-induced airway inflammation. Inflamm. Res. 2017;66:1117–1130. doi: 10.1007/s00011-017-1092-9. PubMed DOI

Jansson D., Dieriks V.B., Rustenhoven J., Smyth L.C.D., Scotter E., Aalderink M., Feng S., Johnson R., Schweder P., Mee E., et al. Cardiac glycosides target barrier inflammation of the vasculature, meninges and choroid plexus. Commun. Biol. 2021;4:260. doi: 10.1038/s42003-021-01787-x. PubMed DOI PMC

Škubník J., Jurášek M., Ruml T., Rimpelová S. Mitotic poisons in research and medicine. Molecules. 2020;25:4632. doi: 10.3390/molecules25204632. PubMed DOI PMC

Škubník J., Pavlíčková V., Ruml T., Rimpelová S. Current perspectives on taxanes: Focus on their bioactivity, delivery and combination therapy. Plants (Basel) 2021;10:569. doi: 10.3390/plants10030569. PubMed DOI PMC

Nejnovějších 20 citací...

Zobrazit více v
Medvik | PubMed

Cardiac Glycosides as Autophagy Modulators

. 2021 Nov 28 ; 10 (12) : . [epub] 20211128

Repurposing Cardiac Glycosides: Drugs for Heart Failure Surmounting Viruses

. 2021 Sep 16 ; 26 (18) : . [epub] 20210916

Quo vadis Cardiac Glycoside Research?

. 2021 May 11 ; 13 (5) : . [epub] 20210511

Najít záznam

Citační ukazatele

Nahrávání dat ...

    Možnosti archivace