Cardiac Glycosides from African Medicinal Plants as Promising Therapeutics

Authors

  • Idayat A. Akinwumi Pharmacognosy Department, Faculty of Pharmacy, Lead City University, Ibadan, Nigeria
  • Owoola A. Ambali Biomedical Sciences Department, School of Medicine and Allied Health Sciences, University of The Gambia, Independence Drive, Banjul.

DOI:

https://doi.org/10.26538/tjpps/v3i2.1

Keywords:

Therapeutics, Pharmacology, Medicinal plants, Cardiac glycosides, Bioactive compounds

Abstract

Cardiac glycosides are a vast class of secondary chemicals found in nature from several sources and have a variety of applications. They also have a similar chemical structure. The present review aims to provide an updated review of cardiac glycosides isolated from African medicinal plants as promising therapeutics. The literature review used several internet resources, including Google, Google Scholar, PubMed, Medline, Research Gate, Web of Sciences, ScienceDirect, and SciFinder using the search terms "cardiac glycosides," "African medicinal plants," "natural products," "pharmacology," "isolated compounds," and "bioactivity". Cardiac glycosides are particularly prevalent in the families Apocynaceae and Asclepiadaceae. Several cardiac glycosides with known pharmacological properties, including cytotoxicity, antiviral, enzyme-inhibitory, anti-inflammatory, and neurotoxic properties, have been identified from African medicinal plants. Despite the numerous pharmacological activities of cardiac glycosides, the toxic side effects of several of these drugs may severely limit their therapeutic usage in humans. It was discovered that there was limited information on the isolation and characterisation of cardiac glycosides from plants in West Africa and the rest of the world while evaluating the literature on the pharmacological actions of cardiac glycosides. The lack of data on this molecule might result in knowledge extinction and prevent biological experiments on the secondary metabolite. Future studies should concentrate on the plants that have not yet been investigated to possibly isolate new cardiac glycosides and other kinds of chemicals. So, numerous biological functions may be tested on isolated molecules.

Metrics

Metrics Loading ...

References

Alsayegh AA, Abusudah WF, Almohmadi NH, Shaheen HM, Singh TG, De Waard M, Khan A. Assessment of Iris albicans lange as potential antimicrobial and analgesic agent. Molecules 2023; 18(1),e0280127. https://doi: 10.3390/molecules27217340 10.1371/journal.pone.0280127

Batiha GE, Akhtar N. Bioactive Compounds, Pharmacological Actions, and Pharmacokinetics of Genus Acacia 2022; 27(21). https://doi:10.3390/molecules27217340

Zhang X, Wang X, Zhang Y, Wang F, Zhang C, Li X. Development of isopentenyl phosphate kinases and their application in terpenoid biosynthesis. Biotechnol Adv 2023; 64. 108124. doi: a10.1016/j.biotechadv.2023.108124

Thirumurugan D, Cholarajan A, Raja S, Vijayakumar R. An Introductory Chapter: secondary metabolites. In book: Secondary metabolites, sources, and Applications. 2018; https://doi: 10.5772/intechopen. 79766

Botelho AFM, Pierezan F, Soto-Blanco B, Melo MM. A review of cardiac glycosides: structure, toxicokinetics, clinical signs, diagnosis, and antineoplastic potential, Toxicon. 2018; https://doi.org/10.1016/j.toxicon. 11.429.

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

Bhusare BP, John CK, Bhatt VP, Nikam TD. In vitro propagation of Digitalis lanata Ehrh. through direct shoot regeneration— A source of cardiotonic glycosides. Ind Crop Prod. 2018; 121:313–319. https://doi.org/10.1016/j.indcrop.2021114167.

Curfman G. Digitalis glycosides for heart rate control in atrial fibrillation. JAMA 2020; 324:2508.

Balderas-Lopez JL, Barbonetti S, Pineda-Rosas EL, Tavares-Carvalho JC, Navarrete A. Cardiac glycosides from Cascabela thevetioides by HPLC-MS analysis. Rev Bras Farmacogn 2019; 29:441–444. https://doi.org/10.1016/j.bjp.2019.04.008.

Qi J, Zulfiker AHM, Li C, Good D, Wei MQ. The Development of toad toxins as potential therapeutic agents. Toxins 2018; 10:336. https://doi: 10.3390/toxins10080336

Skubnik J, Pavlickova V, Rimpelova S. Cardiac Glycosides as Immune System Modulators. Biomolecules 2021; 11:659. https://doi.org/10.3390/biom11050659.

Ayogu JI, Odoh AS. Prospects and Therapeutic Applications of Cardiac Glycosides in Cancer Remediation. ACS Comb Sci, 2020; 22(11), 543-553. https://doi.org/ 10.1021/acscombsci.0c00082

El-Seedi, HR, Khalifa SAM, Taher EA, Farag MA, Saeed A, Gamal M, Efferth T. Cardenolides: Insights from chemical structure and pharmacological utility. Pharmacol Res, 2019; 141, 123-175. doi: 10.1016/j.phrs.2018.12.015

Riaz T, Akram M, Laila U, Zainab R, Khalil MT, Iftikhar M, Sfera A. Therapeutic applications of glycosides obtained from medicinal plants. Int Arch Int Med 2023; 10(8).

Boff L, Persich L, Brambila P, Ottoni FM, Munkert J, Ramos GS, Soares-Viana AR, Kreis W, Braga FC, Alves RJ. Investigation of the cytotoxic activity of two novel digitoxigenin analogues on H460 lung cancer cells. Anti-Cancer Drugs 2020; 31:452–462.

Ren Y, Wu S, Burdette JE, Cheng X, Kinghorn AD. Structural insights into the interactions of digoxin and Na+/K+-ATPase and other targets for the inhibition of cancer cell proliferation. Molecules, 2021; 26(12):3672.

Soto-Blanco B. Cardiac Glycosides Encyclopedia of Molecular Pharmacology 2022; (pp. 410-414): Springer.

Kreis W, Muller-Uri F. Biochemistry of sterols, cardiac glycosides, brassinosteroids, phytoecdysteroids, and steroid saponins, Annu Plant Rev. 2010; 40:304.

Kreis W. The foxgloves (Digitalis) revisited, Planta Med. 2017; 83:962. https://doi.org/10.1055/s-0043-111240.

Temilova SV, Kitashov AV, Nosov AM. Cardiac Glycosides: Distribution, Properties and Specificity of Formation in Plant Cell and Organ Cultures in vitro. Russian J Plant Physiol. 2022; 69:41. https://doi.org/10.1134/S1021443722030165.

Cuny E. Bioactive Ingredients of Helleborus niger L.(Christmas Rose): The Renaissance of an Old Medicinal Herb—A Review. Nat Prod Comm. 2023; 18(9):1934578X231201053.

Botelho AFM, Pierezan F, Soto-Blanco B, Melo MM. A review of cardiac glycosides: Structure, toxicokinetics, clinical signs, diagnosis and antineoplastic potential. Toxicon 2019; 158:63-68.

Tiamiyu AM, Okocha RC, Okunlade OA, Olatoye IO, Adedeji O. Phytochemical Constituents, Nutritional and Antibacterial Potentials of Selected Medicinal Plants 2023; 28(1):1-9. https://doi.org/10.22146/mot.78700.

Morsy N. Cardiac Glycosides in Medicinal Plants. Intech 2017 https://dx.doi.org/10.5772/65963.

Ekalu A, Ayo RGO, James HD, Hamisu I. A mini-review on the phytochemistry and biological activities of selected Apocynaceae plants. J Herbmed Pharmacol 2019; 8(4):269-273.

Sarkar AK. Emerging Trends of Bioscience Research 2019.

Saket K, Afshari JT, Saburi E, Yousefi M, Salari R. Therapeutic Aspects of Squill; An Evidence-Based Review. Curr Drug Discov Technol, 2020; 17(3):318-324. https://doi: 10.2174/1570163816666190125154745.

Steyn PS, van Heerden RF. Bufadienolides of plant and animal origin. Nat Prod Rep 1998; 15:397–413. https://doi:10.1039/A815397Y.

Khalaf H. Laboratory of Pharmacognosy College of Pharmacy, Al Bayan University Lab. 4 PART 1/ The chemical tests for cardioactive glycosides. Pharmacognosy Conference 2021.https://doi :10.13140/RG.2.2.12088.78084.

Mohammadhosseini M, Frezza C, Venditti A, Mahdavi B. An overview of the genus Aloysia palau (Verbenaceae): Essential oil composition, ethnobotany and biological activities. Nat Prod Res 2021 https://doi: org/10.108 0/14786419.2021.1907576.

Tyavambiza C, Dube P, Goboza M, Meyer S, Madiehe AM, Meyer M. Wound Healing Activities and Potential of Selected African Medicinal Plants and Their Synthesized Biogenic Nanoparticles. Plant (Basel), 2021; 10(12). https://doi: 10.1007/s11240-023-02485-8.

3390/plants10122635

Jeyasri R, Muthuramalingam P, Karthick K, Shin H, Choi SH, Ramesh M. Methyl jasmonate and salicylic acid as powerful elicitors for enhancing the production of secondary metabolites in medicinal plants: an updated review. Plant Cell Tissue Organ Cult 2023; 153(3):447-458. https://doi: 10.1007/s11240-023-02485-8.

Mohammadhosseini M, Venditti A, Sarker SD, Nahar L, Akbarzadeh A. The genus Ferula: Ethnobotany, phytochemistry, and bioactivities- a review. Ind Crop Prod. 2019; 129:350-394. https://doi.org/10.1016/j.indecrop.2018.12.012.

Akinwumi IA, Sonibare MA. Sphenocentrum jollyanum Pierre (Menispermaceae): From traditional medicine to pharmacological activity and chemical constituents. Trends Phytochem Res 2022; 6(4):301-313. https://doi: 10.30495/tpr.2022.1961991.1268.

Cock I, Mavuso N, Van Vuuren S. A Review of Plant-Based Therapies for the Treatment of Urinary Tract Infections in Traditional Southern African Medicine. Evidence- Based Compl Alter Med 2021; 7341124. https://doi:10.1155/2021/7341124.

Sitoe E, Van Wyk BE. An inventory and analysis of the medicinal plants of Mozambique. J Ethnopharmacol.2024;319

(2): 117137.https://doi:10.1155/2021/7341124.

Oguntibeju OO. Medicinal plants with anti-inflammatory activities from selected countries and regions of Africa. J Inflamm Res. 2018; 11:307-317. https://doi: 10.2147/jir.s167789

Okaiyeto K, Oguntibeju OO. African Herbal Medicines: Adverse Effects and Cytotoxic Potentials with Different Therapeutic Applications. Int J Environ Res Public Health. 2021; 18(11). https://doi: 10.3390/ijerph18115988.

Mahomoodally MF. Traditional medicines in Africa: an appraisal of ten potent African medicinal plants. Evid-Based Complementary Altern Med. 2013; 1-14. https://doi.10.1155/2013/617459.

Fajinmi OO, Olarewaju OO, Staden JV. Traditional use of medicinal and aromatic plants in Africa. In book: Medicinal and Aromatic Plants of the World. 2017 Volume 3. https://doi: 10:1007/978-94-024-1120-1-3.

Heinrich M, Mah J, Amirkia V. Alkaloids Used as Medicines: Structural Phytochemistry Meets Biodiversity—An Update and Forward Look. Molecules 2021; 26:1836. https://doi.org/10.3390/ molecules26071836.

Fouad YA, Aanei C. Revisiting the hallmarks of cancer. Am J Cancer Res. 2017; 7:1016–1036.

Kumavath R, Paul S, Pavithran H, Paul MK, Ghosh P, Barh D, Azevedo V. Emergence of Cardiac Glycosides as Potential Drugs: Current and Future Scope for Cancer Therapeutics. Biomolecules 2021; 11:1275. https://doi.org /10.3390/biom11091275.

Reddy D, Ghosh P, Kumavath R. Strophanthidin attenuates MAPK, PI3K/AKT/mTOR, and Wnt/β-catenin signaling pathways in human cancers. Front Oncol 2020; 9:1469.

Reddy D, Kumavath R. Anticancer and Antiviral Properties of Cardiac Glycosides: A Review to Explore the Mechanism of Actions. Molecules 2020; 25(16). https://doi: 10.3390/molecules25163596

Al-Snafi AE. Bioactive ingredients and pharmacological effects of Nerium oleander. IOSR J Pharm 2020; 10(9):19-32.

Mekhail T, Kaur H, Ganapathi R, Budd GT, Elson P, Bukowski RM. Phase 1 trial of Anvirzel™ in patients with refractory solid tumors. Investigational new drugs, 2006; 24: 423-427.

Geng X, Wang F, Tian D, Huang L, Streator E, Zhu J, Kurihara H, He R, Yao X, Zhang Y. Cardiac glycosides inhibit cancer through Na/K-ATPase-dependent cell death induction. Biochem Pharmacol. 2020; 182:114226. https://doi: 10.1016/j.bcp2020.114226.

Tian DM, Cheng HY, Jiang MM, Shen WZ, Tang JS, Yao XS. Cardiac glycosides from the seeds of Thevetia peruviana. J Nat Prod. 2016; 79(1):38-50. https://doi: 10.1046/j.1365-3156.1999.00397.x.

Li H, Zhou H, Wang D, Qiu J, Zhou Y, Li X, Rosenfeld MG, Ding S, Fu XD. Versatile pathway-centric approach based on high-throughput sequencing to anticancer drug discovery. Proc Natl Acad Sci. 2012; 109(12):4609-4614. https://doi: 10.1073/pnas. 1200305109.

Feng Q, Leong WS, Liu L, Chan WI. Peruvoside, a cardiac glycoside, induces primitive myeloid leukemia cell death. Molecules 2016; 21(4):534.

Banuls MY, Katz A, Miklos W, Cimmino A, Tal DM, Ainbinder E, Zehl M, Urban E, Evidente A, Kopp B. Hellebrin and its aglycone form hellebrigenin display similar in vitro growth inhibitory effects in cancer cells and binding profiles to the alpha subunits of the Na+/K+ ATPase. Molecular cancer 2013; 12(1):1-14. https://doi.org/10.1186/1476-4598-12-33.

Brady HJ. Apoptosis methods and protocols. 2004 Springer Volume 282.

Kelly R, Daniels EG, Spaulding LB. Cytotoxicity of cardiac principles. J Med Chem 1965; 8(4):547-548. https://doi: 10.1021/jm00328a037.

An N, Sun Y, Ma L, Shi S, Zheng X, Feng W, Shan Z, Han Y, Zhao L, Wu H. Helveticoside Exhibited p53-dependent anticancer activity against colorectal cancer. Arch Med Res. 2020; 51(3):224-232. https://doi.org/10.1016/j.arcmed.2020.02007.

Ambali OA. Bioassay-led isolation of cytotoxic compounds from extracts of Aframomum melegueta (Roscoe) K. Schum. seeds and Strophanthus hispidus Dc. whole plant. 2021; http://hdl.handle.net/123456789/1267.

Kim BY, Lee J, Kim NS. Helveticoside is a biologically active component of the seed extract of Descurainia sophia and induces reciprocal gene regulation in A549 human lung cancer cells. BMC genomics 2015; 16(1):1-14. https://doi: 10.1186/s12864-015-1918-1.

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. https://doi:10.3390/molecules25163596.

Guerrero A, Herranz N, Sun B, Wagner V, Gallage S, Guiho R, Wolter K, Withers DJ, Gil J. Cardiac glycosides are broad-spectrum senolytics. Nat Metabol. 2019; 1(11):1074–1088. https://doi: 10.1038/s42255-019-0122-z.

Hou Y, Shang C, Meng T, Lou W. Anticancer potential of cardiac glycosides and steroid-azole hybrids. Steroids 2021:171. https://doi: 10.1016/j.steroids.2021.108852.

Ayogu JI, Odoh AS. Prospects and Therapeutic Applications of Cardiac Glycosides in Cancer Remediation. ACS Comb Sci 2020; 22:543–553. https://doi.org/10.1021/acscombsci.0c0082.

Wu KX, Yogarajah T, Loe MWC, Kaur P, Lee RCH, Mok CK, Wong YH, Phuektes P, Yeo LS, Chow VTK, Tan YW, Chu JJH. The host-targeting compound peruvoside has a broad-spectrum antiviral activity against positive-sense RNA viruses. Acta Pharm Sin B 2023; 13(5):2039-2055. https://doi.org/10.1016/j.apsb.2023.03.015.

Wu KX, Yogarajah T, Loe MWC, Kaur P, Lee RCH, Mok CK, Wong YH, Phuektes P, Wu PL, Hsu YL, Wu TS, Bastow KF, Lee KH. Kalanchosides A− C, New Cytotoxic Bufadienolides from the Aerial Parts of Kalanchoe gracilis. Org Lett. 2006; 8(23):5207-5210. https://doi: 10.1021/ol061873m. PMID: 17078679.

Bhatia M, Manchanda S, Roy SB. Haemodynamic studies with peruvoside in human congestive heart failure. Br Med J. 1970; 3(5725):740-743.

Shandell MA, Capatina AL, Lawrence SM, Brackenbury WJ, Lagos D. Inhibition of the Na+/K+-ATPase by cardiac glycosides suppresses expression of the IDO1 immune checkpoint in cancer cells by reducing STAT1 activation. J Biol Chem 2022; 298(3).

David MNV, Shetty M. Digoxin In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK556025.

Manna SK, Sah NK, Newman RA, Cisneros A, Aggarwal BB. Oleandrin suppresses activation of nuclear transcription factor-kappaB, activator protein-1, and c-Jun NH2-terminal kinase. Cancer Res 2000; 60(14):3838-3847. PMID: 10919658.

Zhao M, Bai L, Wang L, Toki A, Hasegawa T, Kikuchi M, Abe M, Sakai J, Hasegawa R, Bai Y, Mitsui T, Ogura H, Kataoka T, Oka S, Tsushima H, Kiuchi M, Hirose K, Tomida A, Tsuruo T, Ando M. Bioactive cardenolides from the stems and twigs of Nerium oleander. J Nat Prod. 2007; 70(7):1098-103.https://doi: 10.1021/np068066g.

Kohls S, Scholz-Bottcher BM, Teske J, Zark P, Rullkotter J. Cardiac glycosides from Yellow Oleander (Thevetia peruviana) seeds. Phytochem. 2012; 75:114-127.

Henn D, Venter A, Botha C. In vitro cytotoxicity induced by the bufadienolides 1α, 2α-epoxyscillirosidine and lanceotoxin b on rat myocardial and mouse neuroblastoma cell lines. Toxins 2019; 11(1):14. https://doi: 10.3390/toxins11010014.

El-Seedi HR, Burman R, Mansour A, Turki Z, Boulos L, Gullbo J, Goransson U. The traditional medical uses and cytotoxic activities of sixty-one Egyptian plants: discovery of an active cardiac glycosides from Urginea maritima. J Ethnopharmacol. 2013; 145(3):746-757. https://doi: 10.1016/j.jep.2012.12.007.

Tofighi Z, Saeidi G, Hadjiakhoondi A, Yassa N. Determination of cardiac glycosides and total phenols in different generations of Securigera securidaca suspension culture. Res J Pharmacog. 2016; 3(2):25-31

Downloads

Published

2024-05-04

How to Cite

Akinwumi, I. A., & Ambali, O. A. (2024). Cardiac Glycosides from African Medicinal Plants as Promising Therapeutics. Tropical Journal of Phytochemistry and Pharmaceutical Sciences, 3(2), 158–167. https://doi.org/10.26538/tjpps/v3i2.1