Phytochemical Contents, Biological Activities and Therapeutic Applications
of Hedera Helix (Ivy Leaf) Extracts: A Review

Aya      Shokry; Riham      El-Shiekh; Gehan      Kamel; Amer      Ramadan
doi:10.2174/2210315511666210917111801
Abstract

Background: Herbs have long been used as natural therapeutics, and recent controlled clinical studies have confirmed some of the presumed benefits. Hedera helix(ivy leaves) is a valuable common form related to the family Araliaceae. Many herbal preparations include extracts from their leaves as the principle active ingredient.
Objective: The objective of this article is to summarize the pharmacological activities and phytochemical screening of H. helix.
Methods: To prepare this article, the data was collected from different sources, including books, thesis, research and etc.
Results: The all-published studies depend on isolation, identification, and characterization of different active constituents of H. helix leaves, followed by the determination of biological activities in vivo and in vivo. Chemical screening has shown that H. helix leaves are a rich source of phytochemicals demonstrating therapeutic activities, such as sterols, tannins, terpenoids, glycosides, phenols, emetine alkaloids, flavonoids, saponins, volatile and fixed oils, vitamins, carbohydrates, reducing sugars, and minerals. Further, studies of disease models and clinical trials have demonstrated anti- inflammatory, analgesic, cough suppressant, expectorant, anticancer, antimicrobial, anticoagulant, and smooth muscle relaxant activities.
Conclusion: This review summarizes the bioactive constituents of H. helix leaves and their underlying pharmacological mechanisms, clinical efficacies, and safety profiles. We also suggest potential therapeutic uses for COVID-19.
Keywords: Hedera helix, Ivy leaves, LD₅₀, therapeutic, biological activities, chemical constituents.
Graphical Abstract

[1] 
Al-Snafi, A.E. Chemical constituents and pharmacological effects of Dalbergia sissoo - A review. IOSR J. Pharm.,  2017, 7(2), 59-71.
[http://dx.doi.org/10.9790/3013-0702015971] 
[2] 
Moni, J.N.R.; Adnan, M.; Tareq, A.M.; Kabir, M.I.; Reza, A.S.M.A.; Nasrin, M.S.; Chowdhury, K.H.; Sayem, S.A.J.; Rahman, M.A.; Alam, A.K.; Alam, S.B.; Sakib, M.A.; Oh, K.K.; Cho, D.H.; Capasso, R. Therapeutic potentials of Syzygium fruticosum fruit (seed) reflected into an array of pharmacological assays and prospective receptors-mediated pathways. Life (Basel),  2021, 11(2), 155-176.
[http://dx.doi.org/10.3390/life11020155] [PMID: 33671381] 
[3] 
Fahad, F.I.; Barua, N.; Islam, M.S.; Sayem, S.A.J.; Barua, K.; Uddin, M.J.; Chy, M.N.U.; Adnan, M.; Islam, M.N.; Sayeed, M.A.; Emran, T.B.; Simal-Gandara, J.; Pagano, E.; Capasso, R. Investigation of the pharmacological properties of Lepidagathis hyalina nees through experimental approaches. Life (Basel),  2021, 11(3), 180-196.
[http://dx.doi.org/10.3390/life11030180] [PMID: 33668978] 
[4] 
Goni, O.; Khan, M.F.; Rahman, M.M.; Hasan, M.Z.; Kader, F.B.; Sazzad, N.; Sakib, M.A.; Romano, B.; Haque, M.A.; Capasso, R. Pharmacological insights on the antidepressant, anxiolytic and aphrodisiac potentials of Aglaonema hookerianum Schott. J. Ethnopharmacol.,  2021, 268, 113664.
[http://dx.doi.org/10.1016/j.jep.2020.113664] [PMID: 33278545] 
[5] 
Islam, N.; Khan, M.F.; Khatun, M.R.; Arshad, L.; Lyzu, C.; Cacciola, N.A.; Capasso, R.; Haque, M.A. Neuropharmacological insights of African oil palm leaf through experimental assessment in rodent behavioral model and computer-aided mechanism. Food Biosci.,  2021, 40, 100881.
[http://dx.doi.org/10.1016/j.fbio.2021.100881] 
[6] 
Khan, M.F.; Kader, F.B.; Arman, M.; Ahmed, S.; Lyzu, C.; Sakib, S.A.; Tanzil, S.M.; Zim, A.F.M.I.U.; Imran, M.A.S.; Venneri, T.; Romano, B.; Haque, M.A.; Capasso, R. Pharmacological insights and prediction of lead bioactive isolates of Dita bark through experimental and computer-aided mechanism. Biomed. Pharmacother.,  2020, 131, 110774.
[http://dx.doi.org/10.1016/j.biopha.2020.110774] [PMID: 33152933] 
[7] 
Macêdo, N.S.; Silveira, Z.S.; Bezerra, A.H.; Costa, J.G.M.D.; Coutinho, H.D.M.; Romano, B.; Capasso, R.; Cunha, F.A.B.D.; da Silva, M.V. Caesalpinia ferrea C. Mart. (Fabaceae) Phytochemistry, Ethnobotany, and Bioactivities: A Review. Molecules,  2020, 25(17), 3831.
[http://dx.doi.org/10.3390/molecules25173831] [PMID: 32842529] 
[8] 
Bari, M.S.; Khandokar, L.; Haque, E.; Romano, B.; Capasso, R.; Seidel, V.; Haque, M.A.; Rashid, M.A. Ethnomedicinal uses, phytochemistry, and biological activities of plants of the genus Gynura. J. Ethnopharmacol.,  2021, 271, 113834.
[http://dx.doi.org/10.1016/j.jep.2021.113834] [PMID: 33465439] 
[9] 
Salehi, B.; Quispe, C.; Sharifi-Rad, J.; Cruz-Martins, N.; Nigam, M.; Mishra, A.P.; Konovalov, D.A.; Orobinskaya, V.; Abu-Reidah, I.M.; Zam, W.; Sharopov, F.; Venneri, T.; Capasso, R.; Kukula-Koch, W.; Wawruszak, A.; Koch, W. Phytosterols: From preclinical evidence to potential clinical applications. Front. Pharmacol.,  2021, 11, 599959.
[http://dx.doi.org/10.3389/fphar.2020.599959] [PMID: 33519459] 
[10] 
Ahmed, S.; Khan, H.; Aschner, M.; Mirzae, H.; Küpeli Akkol, E.; Capasso, R. Anticancer potential of furanocoumarins: Mechanistic and therapeutic aspects. Int. J. Mol. Sci.,  2020, 21(16), 5622.
[http://dx.doi.org/10.3390/ijms21165622] [PMID: 32781533] 
[11] 
Lucariello, G.; Cicia, D.; Capasso, R. Pharmacological studies on traditional plant-based remedies. Biomedicines,  2021, 9(3), 315.
[http://dx.doi.org/10.3390/biomedicines9030315] [PMID: 33808651] 
[12] 
Silveira, D.; Prieto-Garcia, J.M.; Boylan, F.; Estrada, O.; Fonseca-Bazzo, Y.M.; Jamal, C.M.; Magalhães, P.O.; Pereira, E.O.; Tomczyk, M.; Heinrich, M. COVID-19: Is there evidence for the use of herbal medicines as adjuvant symptomatic therapy? Front. Pharmacol.,  2020, 11, 581840.
[http://dx.doi.org/10.3389/fphar.2020.581840] [PMID: 33071794] 
[13] 
Lutsenko, Y.; Bylka, W.; Matławska, I.; Gavrylyuk, O.; Dworacka, M.; Krawczyk, A.; Brytska, V. Anti-inflammatory, antimicrobial activity and influence on the lungs and bronchus of Hedera helix leaves extracts. Acta Pol. Pharm.,  2017, 74(4), 1159-1166.
[14] 
Sierocinski, E.; Holzinger, F.; Chenot, J.F. Ivy leaf (Hedera helix) for acute upper respiratory tract infections: An updated systematic review. Eur. J. Clin. Pharmacol.,  2021, 77(8), 1113-1122.
[http://dx.doi.org/10.1007/s00228-021-03090-4] [PMID: 33523253] 
[15] 
Yu, H.; Song, L.; Cao, X.; Li, W.; Zhao, Y.; Chen, J.; Li, J.; Chen, Y.; Yu, W.; Xu, Y. Hederagenin attenuates cerebral ischaemia/reperfusion injury by regulating MLK3 signalling. Front. Pharmacol.,  2020, 11, 1173.
[http://dx.doi.org/10.3389/fphar.2020.01173] [PMID: 32848779] 
[16] 
Kruttschnitt, E.; Wegener, T.; Zahner, C.; Henzen-Bücking, S. Assessment of the efficacy and safety of Ivy Leaf (Hedera helix) cough syrup compared with acetylcysteine in adults and children with acute bronchitis. Evid. Based Complement. Alternat. Med.,  2020, 2020, 1910656.
[http://dx.doi.org/10.1155/2020/1910656] [PMID: 32454850] 
[17] 
Al-Snafi, A.E. Pharmacological and therapeutic activities of Hedera helix- A review. IOSR J. Pharm.,  2018, 8(5), 41-53.
[18] 
Ferrara, L.; Naviglio, D.; Faralli, S. Identification of active principles of Hedera helix L. in aqueous extracts. Res. J. Phytochem.,  2013, 114, 170-175.
[19] 
Talari, A.; Hooshyar, H.; Sayaah, M. In vitro effect of various concentrations of Hedera Helix extract and Glucantime on cutaneous Leishmaniosis. Feyz,  1997, 1(2), 61-67.
[20] 
Roşca-Casian, O.; Mircea, C.; Vlase, L.; Gheldiu, A.M.; Teuca, D.T.; Pârvu, M. Chemical composition and antifungal activity of Hedera helix leaf ethanolic extract. Acta Biol. Hung.,  2017, 68(2), 196-207.
[http://dx.doi.org/10.1556/018.68.2017.2.7] [PMID: 28605982] 
[21] 
Chung, Y.S.; Nam, Y.; Lee, J.H. Feasibility of Ivy (Hedra helix) for landscaping in Seoul, Korea. J. Ornam. Hortic.,  2018, 24(4), 424-428.
[http://dx.doi.org/10.14295/oh.v24i4.1250] 
[22] 
Olszanecka-Glinianowicz, M.; Doniec, Z.; Schönknecht, K.; Almgren-Rachtan, A. The herbal medicine containing of ivy leaf dry extract in the treatment of productive cough in children. Wiad. Lek.,  2020, 73(4), 668-673.
[http://dx.doi.org/10.36740/WLek202004108] [PMID: 32731694] 
[23] 
Cwientzek, U.; Ottillinger, B.; Arenberger, P. Acute bronchitis therapy with ivy leaves extracts in a two-arm study. A double-blind, randomised study vs. an other ivy leaves extract. Phytomedicine,  2011, 18(13), 1105-1109.
[http://dx.doi.org/10.1016/j.phymed.2011.06.014] [PMID: 21802921] 
[24] 
Rashed, K.N.Z. Antioxidant activity of Hedera helix L. extracts and the main phytoconstituents. Int. J. Allied Med. Sci. Clin. Res.,  2013, 1(2), 62-64.
[25] 
Al-Snafi, A.E. Traditional uses of Iraqi medicinal plants. IOSR J. Pharm.,  2018, 8(8), 32-95.
[26] 
DeFilipps, R.A.; Krupnick, G.A. The medicinal plants of Myanmar. PhytoKeys,  2018, 102(102), 1-341.
[http://dx.doi.org/10.3897/phytokeys.102.24380] [PMID: 30002597] 
[27] 
Brussell, D.E. Medicinal plants of Mt. Pelion, Greece. Econ. Bot.,  2004, 58, 174-202.
[http://dx.doi.org/10.1663/0013-0001(2004)58[S174:MPOMPG]2.0.CO;2] 
[28] 
Kültür, S. Medicinal plants used in Kirklareli Province (Turkey). J. Ethnopharmacol.,  2007, 111(2), 341-364.
[http://dx.doi.org/10.1016/j.jep.2006.11.035] [PMID: 17257791] 
[29] 
Lutsenko, Y.; Bylka, W.; Matlawska, I.; Darmohray, R. Hedera helix as a medicinal plant. Herba Pol.,  2010, 56, 83-96.
[30] 
Delmas, F.; Di Giorgio, C.; Elias, R.; Gasquet, M.; Azas, N.; Mshvildadze, V.; Dekanosidze, G.; Kemertelidze, E.; Timon- David, P. Antileishmanial activity of three saponins isolated from ivy, alpha-hederin, beta-hederin and hederacolchiside A1, as compared to their action on mammalian cells cultured in vitro. Planta Med.,  2000, 66(4), 343-347.
[http://dx.doi.org/10.1055/s-2000-8541] [PMID: 10865451] 
[31] 
Saiah, H.; Allem, R.; El Kebir, F.Z. Antioxidant and antibacterial activities of six Algerian medicinal plants. Int. J. Pharm. Pharm. Sci.,  2016, 8(1), 367-374.
[32] 
Yu, M.; Liu, J.; Li, L.; Xu, H.; Xing, Y.; Zhao, Y.; Yu, Z. Pharmacokinetic parameters of three active ingredients hederacoside C, hederacoside D, and ɑ-hederin in Hedera helix in rats. J. Sep. Sci.,  2016, 39(17), 3292-3301.
[http://dx.doi.org/10.1002/jssc.201600523] [PMID: 27377040] 
[33] 
Medeiros, J.R.; Medeiros, H.; Mascarenhas, C.; Davin, L.B.; Lewis, N.G. Bioactive components of Hedera helix. Arquipélago.,  2002, 19A, 27-32.
[34] 
Hillman, J.R.; Young, I.; Knights, B.A. Abscisic acid in leaves of Hedera helix L. Planta,  1974, 119(3), 263-266.
[http://dx.doi.org/10.1007/BF00429050] [PMID: 24442503] 
[35] 
Rai, A. The antiinflammatory and antiarthritic properties of ethanol extract of Hedera helix. Indian J. Pharm. Sci.,  2013, 75(1), 99-102.
[http://dx.doi.org/10.4103/0250-474X.113537] [PMID: 23901168] 
[36] 
Schulte-Michels, J.; Keksel, C.; Häberlein, H.; Franken, S. Anti-inflammatory effects of ivy leaves dry extract: Influence on transcriptional activity of NFκB. Inflammopharmacology,  2019, 27(2), 339-347.
[http://dx.doi.org/10.1007/s10787-018-0494-9] [PMID: 29748881] 
[37] 
Holzinger, F.; Chenot, J.F. Systematic review of clinical trials assessing the effectiveness of ivy leaf (Hedera helix) for acute upper respiratory tract infections. Evid. Based Complement. Alternat. Med.,  2011, 2011, 382789.
[http://dx.doi.org/10.1155/2011/382789] [PMID: 20976077] 
[38] 
Sieben, A.; Prenner, L.; Sorkalla, T.; Wolf, A.; Jakobs, D.; Runkel, F.; Häberlein, H. α-hederin, but not hederacoside C and hederagenin from Hedera helix, affects the binding behavior, dynamics, and regulation of β 2-adrenergic receptors. Biochemistry,  2009, 48(15), 3477-3482.
[http://dx.doi.org/10.1021/bi802036b] [PMID: 19278262] 
[39] 
Lang, C.; Röttger-Lüer, P.; Staiger, C. A valuable option for the treatment of respiratory diseases: review on the clinical evidence of the Ivy Leaves Dry Extract EA 575(R). Planta Med.,  2015, 81(12-13), 968-974.
[http://dx.doi.org/10.1055/s-0035-1545879] [PMID: 25875509] 
[40] 
Zeil, S.; Schwanebeck, U.; Vogelberg, C. Tolerance and effect of an add-on treatment with a cough medicine containing ivy leaves dry extract on lung function in children with bronchial asthma. Phytomedicine,  2014, 21(10), 1216-1220.
[http://dx.doi.org/10.1016/j.phymed.2014.05.006] [PMID: 24916707] 
[41] 
Greunke, C.; Hage-Hülsmann, A.; Sorkalla, T.; Keksel, N.; Häberlein, F.; Häberlein, H. A systematic study on the influence of the main ingredients of an ivy leaves dry extract on the β2-adrenergic responsiveness of human airway smooth muscle cells. Pulm. Pharmacol. Ther.,  2015, 31, 92-98.
[http://dx.doi.org/10.1016/j.pupt.2014.09.002] [PMID: 25234924] 
[42] 
Johnson, M. Beta2-adrenoceptors: Mechanisms of action of beta2-agonists. Paediatr. Respir. Rev.,  2001, 2(1), 57-62.
[http://dx.doi.org/10.1053/prrv.2000.0102] [PMID: 16263481] 
[43] 
Giembycz, M.A.; Newton, R. Beyond the dogma: novel β2-adrenoceptor signalling in the airways. Eur. Respir. J.,  2006, 27(6), 1286-1306.
[http://dx.doi.org/10.1183/09031936.06.00112605] [PMID: 16772391] 
[44] 
Schulte-Michels, J.; Wolf, A.; Aatz, S.; Engelhard, K.; Sieben, A.; Martinez-Osuna, M.; Häberlein, F.; Häberlein, H. α-Hederin inhibits G protein-coupled receptor kinase 2-mediated phosphorylation of β2-adrenergic receptors. Phytomedicine,  2016, 23(1), 52-57.
[http://dx.doi.org/10.1016/j.phymed.2015.12.001] [PMID: 26902407] 
[45] 
Gepdiremen, A.; Mshvildadze, V.; Süleyman, H.; Elias, R. Acute anti-inflammatory activity of four saponins isolated from ivy: alpha-hederin, hederasaponin-C, hederacolchiside-E and hederacolchiside-F in carrageenan-induced rat paw edema. Phytomedicine,  2005, 12(6-7), 440-444.
[http://dx.doi.org/10.1016/j.phymed.2004.04.005] [PMID: 16008120] 
[46] 
Kim, H.R.; Lee, D.M.; Lee, S.H.; Seong, A.R.; Gin, D.W.; Hwang, J.A.; Park, J.H. Chlorogenic acid suppresses pulmonary eosinophilia, IgE production, and Th2-type cytokine production in an ovalbumin-induced allergic asthma: Activation of STAT-6 and JNK is inhibited by chlorogenic acid. Int. Immunopharmacol.,  2010, 10(10), 1242-1248.
[http://dx.doi.org/10.1016/j.intimp.2010.07.005] [PMID: 20637839] 
[47] 
Zhang, X.; Huang, H.; Yang, T.; Ye, Y.; Shan, J.; Yin, Z.; Luo, L. Chlorogenic acid protects mice against lipopolysaccharide-induced acute lung injury. Injury,  2010, 41(7), 746-752.
[http://dx.doi.org/10.1016/j.injury.2010.02.029] [PMID: 20227691] 
[48] 
Hocaoglu, A.B.; Karaman, O.; Erge, D.O.; Erbil, G.; Yilmaz, O.; Kivcak, B.; Bagriyanik, H.A.; Uzuner, N. Effect of Hedera helix on lung histopathology in chronic asthma. Iran. J. Allergy Asthma Immunol.,  2012, 11(4), 316-323.
[PMID: 23264408] 
[49] 
Schulte-Michels, J.; Runkel, F.; Gokorsch, S.; Häberlein, H. Ivy leaves dry extract EA 575® decreases LPS-induced IL-6 release from murine macrophages. Pharmazie,  2016, 71(3), 158-161.
[PMID: 27183712] 
[50] 
dos Santos, M.D.; Almeida, M.C.; Lopes, N.P.; de Souza, G.E.P. Evaluation of the anti-inflammatory, analgesic and antipyretic activities of the natural polyphenol chlorogenic acid. Biol. Pharm. Bull.,  2006, 29(11), 2236-2240.
[http://dx.doi.org/10.1248/bpb.29.2236] [PMID: 17077520] 
[51] 
Guardia, T.; Rotelli, A.E.; Juarez, A.O.; Pelzer, L.E. Anti-inflammatory properties of plant flavonoids. Effects of rutin, quercetin and hesperidin on adjuvant arthritis in rat. Farmaco,  2001, 56(9), 683-687.
[http://dx.doi.org/10.1016/S0014-827X(01)01111-9] [PMID: 11680812] 
[52] 
Süleyman, H.; Mshvildadze, V.; Gepdiremen, A.; Elias, R. Acute and chronic antiinflammatory profile of the ivy plant, Hedera helix, in rats. Phytomedicine,  2003, 10(5), 370-374.
[http://dx.doi.org/10.1078/0944-7113-00260] [PMID: 12834000] 
[53] 
Mandade, R.J.; Choudhuri, A.; Mashirkar, V.; Sakarkar, D. Analgesic and antiinflammatory activities of Hedera helix leaf extract. Pharm. Glob.,  2010, 1(4), 1-3.
[54] 
Quetin-Leclercq, J.; Elias, R.; Balansard, G.; Bassleer, R.; Angenot, L. Cytotoxic activity of some triterpenoid saponins. Planta Med.,  1992, 58(3), 279-281.
[http://dx.doi.org/10.1055/s-2006-961456] [PMID: 1409985] 
[55] 
Danloy, S.; Quetin-Leclercq, J.; Coucke, P.; De Pauw-Gillet, M.C.; Elias, R.; Balansard, G.; Angenot, L.; Bassleer, R. Effects of alpha-hederin, a saponin extracted from Hedera helix, on cells cultured in vitro. Planta Med.,  1994, 60(1), 45-49.
[http://dx.doi.org/10.1055/s-2006-959406] [PMID: 8134416] 
[56] 
Bun, S.S.; Elias, R.; Baghdikian, B.; Ciccolini, J.; Ollivier, E.; Balansard, G. Alpha-hederin potentiates 5-FU antitumor activity in human colon adenocarcinoma cells. Phytother. Res.,  2008, 22(10), 1299-1302.
[http://dx.doi.org/10.1002/ptr.2483] [PMID: 18546204] 
[57] 
Wang, J.; Zhao, X.Z.; Qi, Q.; Tao, L.; Zhao, Q.; Mu, R.; Gu, H.Y.; Wang, M.; Feng, X.; Guo, Q.L. Macranthoside B, a hederagenin saponin extracted from Lonicera macranthoides and its anti-tumor activities in vitro and in vivo. Food Chem. Toxicol.,  2009, 47(7), 1716-1721.
[http://dx.doi.org/10.1016/j.fct.2009.04.034] [PMID: 19406196] 
[58] 
Kuljanabhagavad, T.; Thongphasuk, P.; Chamulitrat, W.; Wink, M. Triterpene saponins from Chenopodium quinoa Willd. Phytochemistry,  2008, 69(9), 1919-1926.
[http://dx.doi.org/10.1016/j.phytochem.2008.03.001] [PMID: 18452959] 
[59] 
Liu, B.X.Z.; Zhou, J.Y.; Li, Y.; Zou, X.; Wu, J.; Gu, J.F.; Yuan, J.R.; Zhao, B.J.; Feng, L.; Jia, X.B.; Wang, R.P. Hederagenin from the leaves of ivy (Hedera helix L.) induces apoptosis in human LoVo colon cells through the mitochondrial pathway. BMC Complement. Altern. Med.,  2014, 14, 412.
[http://dx.doi.org/10.1186/1472-6882-14-412] [PMID: 25342273] 
[60] 
Uddin, G.; Rauf, A.; Qaisar, M.; Rehman, T.U.; Latif, A.; Ali, M. Preliminary Phytochemical Screening and Antimicrobial Activity of Hedera helix L. Middle East J. Sci. Res.,  2011, 8(1), 198-202.
[61] 
Pop, C.E.; Pârvu, M.; Arsene, A.L.; Pârvu, A.E.; Vodnar, D.C.; Tarcea, M.; Toiu, A.M.; Vlase, L. Investigation of antioxidant and antimicrobial potential of some extracts from Hedera helix L. Farmacia,  2017, 65(4), 624-629.
[62] 
Ieven, M.; Vanden Berghe, D.A.; Mertens, F.; Vlietinck, A.; Lammens, E. Screening of higher plants for biological activities. I. Antimicrobial activity. Planta Med.,  1979, 36(4), 311-321.
[PMID: 493400] 
[63] 
Favel, A.; Steinmetz, M.D.; Ollivier, E.; Elias, R.; Régli, P. Screening of triterpenoid saponins for antifungal activity. Planta Med.,  1992, 58(1), A635-A636.
[64] 
Favel, A.; Steinmetz, M.D.; Regli, P.; Vidal-Ollivier, E.; Elias, R.; Balansard, G. In vitro antifungal activity of triterpenoid saponins. Planta Med.,  1994, 60(1), 50-53.
[http://dx.doi.org/10.1055/s-2006-959407] [PMID: 8134417] 
[65] 
Prescott, T.A.; Rigby, L.P.; Veitch, N.C.; Simmonds, M.S. The haploinsufficiency profile of α-hederin suggests a caspofungin-like antifungal mode of action. Phytochemistry,  2014, 101, 116-120.
[http://dx.doi.org/10.1016/j.phytochem.2014.01.022] [PMID: 24569176] 
[66] 
Arif, T.; Bhosale, J.D.; Kumar, N.; Mandal, T.K.; Bendre, R.S.; Lavekar, G.S.; Dabur, R. Natural products--antifungal agents derived from plants. J. Asian Nat. Prod. Res.,  2009, 11(7), 621-638.
[http://dx.doi.org/10.1080/10286020902942350] [PMID: 20183299] 
[67] 
Dissanayake, M.L.M.C. Inhibitory effect of selected medicinal plant extracts on phytopathogenic fungus Fusarium oxysporum (Nectriaceae) Schlecht. Emend. Snyder and Hansen. Annu. Res. Rev. Biol.,  2014, 4(1), 133-142.
[http://dx.doi.org/10.9734/ARRB/2014/5777] 
[68] 
Song, J.; Yeo, S.G.; Hong, E.H.; Lee, B.R.; Kim, J.W.; Kim, J.; Jeong, H.; Kwon, Y.; Kim, H.; Lee, S.; Park, J.H.; Ko, H.J. Antiviral activity of hederasaponin B from Hedera helix against enterovirus 71 subgenotypes c3 and C4a. Biomol. Ther. (Seoul),  2014, 22(1), 41-46.
[http://dx.doi.org/10.4062/biomolther.2013.108] [PMID: 24596620] 
[69] 
Hong, E.H.; Song, J.H.; Shim, A.; Lee, B.R.; Kwon, B.E.; Song, H.H.; Kim, Y.J.; Chang, S.Y.; Jeong, H.G.; Kim, J.G.; Seo, S.U.; Kim, H.; Kwon, Y.; Ko, H.J. Coadministration of Hedera helix L. extract enabled mice to overcome insufficient protection against influenza A/PR/8 virus infection under suboptimal treatment with oseltamivir. PLoS One,  2015, 10(6), e0131089.
[http://dx.doi.org/10.1371/journal.pone.0131089] [PMID: 26098681] 
[70] 
Wang, L.; Wang, Y.; Ye, D.; Liu, Q. Review of the 2019 novel coronavirus (SARS-CoV-2) based on current evidence. Int. J. Antimicrob. Agents,  2020, 55(6), 105948.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105948] [PMID: 32201353] 
[71] 
Barnes, L.A.; Leach, M.; Anheyer, D.; Brown, D.; Carè, J.; Lauche, R.; Medina, D.N.; Pinder, T.A.; Bugarcic, A.; Steel, A. The effects of Hedera helix on viral respiratory infections in humans: A rapid review. Adv. Integr. Med.,  2020, 7(4), 222-226.
[http://dx.doi.org/10.1016/j.aimed.2020.07.012] [PMID: 32837900] 
[72] 
Julien, J.; Gasquet, M.; Maillard, C.; Balansard, G.; Timon-David, P. Extracts of the ivy plant, Hedera helix, and their anthelminthic activity on liver flukes. Planta Med.,  1985, 17(3), 205-208.
[http://dx.doi.org/10.1055/s-2007-969457] [PMID: 4034744] 
[73] 
Tedlaouti, F.; Gasquet, M.; Delmas, F.; Timon-David, P.; Elias, R.; Vidal-Ollivier, E.; Grespin, F.; Balansard, G. Antitrypanosomial activity of some saponins from Calendula arvensis, Hedera helix and Sapindus mukurossi. Planta Med.,  1991, 57(2), A78.
[http://dx.doi.org/10.1055/s-2006-960347] 
[74] 
Majester-Savornin, B.; Elias, R.; Diaz-Lanza, A.M.; Balansard, G.; Gasquet, M.; Delmas, F. Saponins of the ivy plant, Hedera helix, and their leishmanicidic activity. Planta Med.,  1991, 57(3), 260-262.
[http://dx.doi.org/10.1055/s-2006-960086] [PMID: 1896525] 
[75] 
Yakovishin, L.A.; Ertahova, V.A.; Bazyura, E.A. Influence of the triterpene glycosides and their complexes on mollusks. Ukr. Bioorg. Acta,  2006, 2, 22-26.
[76] 
Eguale, T.; Tilahun, G.; Debella, A.; Feleke, A.; Makonnen, E. Haemonchus contortus: In vitro and in vivo anthelmintic activity of aqueous and hydro-alcoholic extracts of Hedera helix. Exp. Parasitol.,  2007, 116(4), 340-345.
[http://dx.doi.org/10.1016/j.exppara.2007.01.019] [PMID: 17382320] 
[77] 
Hooshyar, H.; Talari, S.; Feyzi, F. Therapeutic effect of Hedera helix alcoholic extract against Cutaneous Leishmaniasis caused by Leishmania major in Balb/C mice. Jundishapur J. Microbiol.,  2014, 7(4), e9432.
[http://dx.doi.org/10.5812/jjm.9432] [PMID: 25147703] 
[78] 
Gülçin, I.; Mshvildadze, V.; Gepdiremen, A.; Elias, R. Antioxidant activity of saponins isolated from ivy: Alpha-hederin, hederasaponin-C, hederacolchiside-E and hederacolchiside-F. Planta Med.,  2004, 70(6), 561-563.
[http://dx.doi.org/10.1055/s-2004-827158] [PMID: 15241892] 
[79] 
Jeong, H.G.; Park, H.Y. The prevention of carbon tetrachloride-induced hepatotoxicity in mice by alpha-hederin: inhibiton of cytochrome P450 2E1 expression. Biochem. Mol. Biol. Int.,  1998, 45(1), 163-170.
[PMID: 9635140] 
[80] 
Moshaie-Nezhad, P.; Hosseini, S.M.; Yahyapour, M.; Iman, M.; Khamesipoure, A. Protective effect of ivy leaf extract on paracetamol-induced oxidative stress and nephrotoxicity in mice. J. herbmed. pharmacol.,  2019, 8(1), 64-68.
[81] 
Mulkijanyan, K.; Novikova, Zh.; Sulakvelidze, M.; Getia, M.; Mshvildadze, V.; Dekanosidze, G. Ivy water extracts as gastric ulcer preventive agents. Georgian Med. News,  2013, 224(224), 63-66.
[PMID: 24323967] 
[82] 
Mendel, M.; Chłopecka, M.; Dziekan, N.; Wiechetek, M. The effect of the whole extract of common ivy (Hedera helix) leaves and selected active substances on the motoric activity of rat isolated stomach strips. J. Ethnopharmacol.,  2011, 134(3), 796-802.
[http://dx.doi.org/10.1016/j.jep.2011.01.036] [PMID: 21291987] 
[83] 
Villani, P.; Orsière, T.; Sari-Minodier, I.; Bouvenot, G.; Botta, A. In vitro study of the antimutagenic activity of alphahederin. Ann. Biol. Clin. (Paris),  2001, 59(3), 285-289.
[PMID: 11397676] 
[84] 
Zeng, J.; Huang, T.; Xue, M.; Chen, J.; Feng, L.; Du, R.; Feng, Y. Current knowledge and development of hederagenin as a promising medicinal agent: A comprehensive review. RSC Advances,  2018, 8(24), 188-202.
[http://dx.doi.org/10.1039/C8RA03666G] 
[85] 
Duke, J.A. Handbook of medicinal herbs, 2nd ed; CRC Press: Boca Raton,  2002, p412.
[http://dx.doi.org/10.1201/9781420040463] 
[86] 
Steinmetz, E.F. Hederae helicis folia. Q. J. Crude Drug Res.,  1991, 1, 93-95.
[http://dx.doi.org/10.3109/13880206109087157] 
[87] 
Campbell, W.B.; Gebremedhin, D.; Pratt, P.F.; Harder, D.R. Identification of epoxyeicosatrienoic acids as endothelium-derived hyperpolarizing factors. Circ. Res.,  1996, 78(3), 415-423.
[http://dx.doi.org/10.1161/01.RES.78.3.415] [PMID: 8593700] 
[88] 
Salma, U.; Khan, T.; Shah, A.J. Antihypertensive efficacy of extract of Hedera helix in high salt-induced hypertensive Sprague- Dawley rats. Asian Pac. J. Trop. Biomed.,  2018, 11(8), 473-479.
[http://dx.doi.org/10.4103/1995-7645.240083] 
[89] 
Yi, S.; Xia, L.; Lenaghan, S.C.; Sun, L.; Huang, Y.; Burris, J.N.; Stewart, C.N., Jr; Zhang, M. Bio-synthesis of gold nanoparticles using English ivy (Hedera helix). J. Nanosci. Nanotechnol.,  2013, 13(3), 1649-1659.
[http://dx.doi.org/10.1166/jnn.2013.7183] [PMID: 23755570] 
[90] 
Abbasifar, A.; Ghani, S.; Irvani, M.A.; Rafiee, B.; Kaji, B.V.; Akbaril, A. Antibacterial activity of silver nanoparticles synthesized by using extracts of Hedera helix. Zahedan J. Res. Med. Sci.,  2019, 19(1), 1-6.
[91] 
Lenaghan, S.C.; Burris, J.N.; Chourey, K.; Huang, Y.; Xia, L.; Lady, B.; Sharma, R.; Pan, C.; LeJeune, Z.; Foister, S.; Hettich, R.L.; Stewart, C.N., Jr; Zhang, M. Isolation and chemical analysis of nanoparticles from English ivy (Hedera helix L.). J. R. Soc. Interface,  2013, 10(87), 20130392-10.
[http://dx.doi.org/10.1098/rsif.2013.0392] [PMID: 23883948] 
[92] 
Burris, J.N.; Lenaghan, S.C.; Zhang, M.; Stewart, C.N. Nanoparticle biofabrication using English ivy (Hedera helix). J. Nanobiotechnology,  2012, 10, 41.
[http://dx.doi.org/10.1186/1477-3155-10-41] [PMID: 23095780] 
[93] 
Huang, Y.; Wang, Y.J.; Wang, Y.; Yi, S.; Fan, Z.; Sun, L.; Lin, D.; Anreddy, N.; Zhu, H.; Schmidt, M.; Chen, Z.S.; Zhang, M. Exploring naturally occurring ivy nanoparticles as an alternative biomaterial. Acta Biomater.,  2015, 25, 268-283.
[http://dx.doi.org/10.1016/j.actbio.2015.07.035] [PMID: 26219859] 
[94] 
Xia, L.; Lenaghan, S.C.; Zhang, M.; Zhang, Z.; Li, Q. Naturally occurring nanoparticles from English ivy: An alternative to metal-based nanoparticles for UV protection. J. Nanobiotechnology,  2010, 8(12), 12.
[http://dx.doi.org/10.1186/1477-3155-8-12] [PMID: 20534157] 
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DOI https://dx.doi.org/10.2174/2210315511666210917111801	Print ISSN 2210-3155
Publisher Name Bentham Science Publisher	Online ISSN 2210-3163
The Natural Products Journal

Phytochemical Contents, Biological Activities and Therapeutic Applications of Hedera Helix (Ivy Leaf) Extracts: A Review

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