IN VITRO ANTIOXIDANT RESPONSE OF MUSCLE TISSUE OF RAINBOW TROUT (ONCORHYNCHUS MYKISS WALBAUM) TREATED WITH EXTRACT FROM LEAVES OF EUROPEAN MISTLETOE (VISCUM ALBUM L.)
Keywords:
European mistletoe (Viscum album L.), extracts, rainbow trout (Oncorhynchus mykiss Walbaum, 2-thiobarbituric acid reactive substances (TBARS), carbonyl derivatives of oxidative modification of proteins, total antioxidant capacity (TAC)
Abstract
Many studies, based on the understanding of the relationship between the generation of reactive oxygen species and antioxidant defences, propose a link with the recent use of mistletoe based on its antioxidant properties, supported by phytochemical and pharmacological data. The uniqueness of mistletoe metabolism, a direct consequence of its hemiparasitism, is used as a key interpretive element to explain its biological properties and guide its consequent therapeutic use.The aim of the present study was to determine the antioxidant activity of extracts derived from the leaves of Viscum album L. using biomarkers of oxidative stress [2-thiobarbituric acid reactive substances (TBARS) as a biomarker of lipid peroxidation, carbonyl derivatives of oxidative modification of proteins, total antioxidant capacity (TAC)] in the muscle tissue of rainbow trout (Oncorhynchus mykissWalbaum) after in vitro treatment with extracts at two final concentrations (5 and 2.5 mg/mL). Our study revealed that treatment with V. album leaf extracts resulted in non-significant changes in TBARS levels in the muscle tissue after in vitro incubation with V. album leaf extracts at final concentrations of 5 and 2.5 mg/mL.The levels of aldehydic derivatives of oxidatively modified proteins in rainbow trout muscle tissue after treatment with V. album leaf extracts at final concentrations of 5 mg/mL were at the same levels as in untreated controls. When muscle tissue was incubated with V. album leaf extracts, the levels of ketonic derivatives were significantly reduced after treatment with extracts at a final concentration of 5 and 2.5 mg/mL compared to untreated samples. TAC levels in rainbow trout muscle tissue were increased after in vitro incubation with V. album leaf extracts (at final concentrations of 5 and 2.5 mg/mL) compared to untreated samples. The results of the current study demonstrated the antioxidant properties of extracts from the leaves of V. album at two final concentrations (5 and 2.5 mg/mL) after incubation with rainbow trout muscle tissue.Further studies should focus on the antioxidant effect of extracts derived from the leaves of Viscum album using other cellular models.
References
1. Aguilar Diaz De Leon J, Borges CR. Evaluation of Oxidative Stress in Biological Samples Using the Thiobarbituric Acid Reactive Substances Assay. J Vis Exp. 2020;(159):10.3791/61122. doi:10.3791/61122.
2. Bartosz G. Total antioxidant capacity. AdvClin Chem. 2003;37:219-292. doi:10.1016/s0065-2423(03)37010-6.
3. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248-254. doi:10.1006/abio.1976.9999.
4. Braedel-Ruoff S. Immunomodulatory effects of Viscum album extracts on natural killer cells: review of clinical trials. ForschKomplementmed. 2010;17(2):63-73. doi:10.1159/000288702.
5. Bussing A. Mistletoe. The genus Viscum. Amsterdam: Hardwood Academic Publishers; 2000.
6. Choi SH, Park KH, Yoon TJ, Kim JB, Jang YS, Choe CH. Dietary Korean mistletoe enhances cellular non-specific immune responses and survival of Japanese eel (Anguilla japonica). Fish Shellfish Immunol. 2008;24(1):67-73. doi:10.1016/j.fsi.2007.08.007.
7. Dubinina EE, Burmistrov SO, Khodov DA, Porotov IG. Okislitel'naiamodifikatsiiabelkovsyvorotkikrovicheloveka, metodeeopredeleniia [Oxidative modification of human serum proteins. A method of determining it]. Vopr Med Khim. 1995;41(1):24-26.
8. Dügenci SK, Arda N, Candan A. Some medicinal plants as immunostimulant for fish. J Ethnopharmacol. 2003;88(1):99-106. doi:10.1016/s0378-8741(03)00182-x.
9. Fukunaga T, Kajikawa I, Nishiya K, Watanabe Y, Suzuki N, Takeya K, Itokawa H. Studies on the constituents of the European mistletoe, Viscum album L. II Chem Pharm Bull. 1988;36(3):1185–1189. doi: 10.1248/cpb.36.1185.
10. Galaktionova LP, Molchanov AV, El'chaninova SA, VarshavskiĭBIa. Sostoianieperekisnogookisleniia u bol'nykh s iazvennoĭbolezn'iuzheludkaidvenadtsatiperstnoĭkishki [Lipid peroxidation in patients with gastric and duodenal peptic ulcers]. Klin Lab Diagn. 1998;(6):10-14.
11. Garg S, Patil UK, Shrivastava TP. Wound healing potential of ViscumArticulumBrm., an ethnomedical plant of Sikkim on rat. Int J Res PhytochemPharmacol. 2012;2:138–142. doi: 10.1186/s13002-017-0148-9.
12. Geetha KM, Murugan V, Pavan Kumar P, Wilson B. Antiepileptic activity of ViscumarticulatumBurm and its isolated bioactive compound in experimentally induced convulsions in rats and mice. Eur J Biomed Pharm Sci. 2018;5:311–318.
13. Grossarth-Maticek R, Kiene H, Baumgartner SM, Ziegler R. Use of Iscador, an extract of European mistletoe (Viscum album), in cancer treatment: prospective nonrandomized and randomized matched-pair studies nested within a cohort study. AlternTher Health Med. 2001;7(3).
14. Gupta G, Kazmi I, Afzal M, Rahman M, Saleem S, Ashraf S, Khusroo MJ, Nazeer K, Ahmed S, Mujeeb M, Ahmed Z, Anwar F. Sedative, antiepileptic and antipsychotic effects of Viscum album L. (Loranthaceae) in mice and rats. J Ethnopharmacol. 2012;141:810–816. doi: 10.1016/j.jep.2012.03.013.
15. Holandino C, Melo MNO, Oliveira AP, Batista JVDC, Capella MAM, Garrett R, Grazi M, Ramm H, Torre CD, Schaller G, Urech K, Weissenstein U, Baumgartner S. Phytochemical analysis and in vitro anti-proliferative activity of Viscum album ethanolic extracts. BMC Complement Med Ther. 2020;20(1):215. doi:10.1186/s12906-020-02987-4.
16. Hussain MA, Khan MQ, Hussain N, Habib T. Antibacterial and antifungal potential of leaves and twigs of Viscum album L. J Med Plants Res. 2011;5:5545–5549.
17. Kamyshnikov VS. A reference work for clinical and biochemical research and laboratory diagnostics. MEDpress-inform, Moscow, 2004.
18. Karagöz A, Kesici S, Vural A, Usta M, Tezcan B, Semerci T, Teker E. Cardioprotective effects of Viscum album L. ssp. album (Loranthaceae) on isoproterenol-induced heart failure via regulation of the nitric oxide pathway in rats. Anatol J Cardiol. 2016;16:923–930. doi: 10.14744/AnatolJCardiol.2016.6780.
19. Karagöz A, Önay E, Arda N, Kuru A. Antiviral potency of mistletoe (Viscum album ssp. album) extracts against human parainfluenza virus type 2 in Vero cells. Phyther Res. 2003;17:560–562. doi: 10.1002/ptr.1163.
20. Khan T, Ali S, Qayyum R, Hussain I, Wahid F, Shah AJ. Intestinal and vascular smooth muscle relaxant effect of Viscum album explains its medicinal use in hyperactive gut disorders and hypertension. BMC Complement Aternative Med. 2016;16:251. doi: 10.1186/s12906-016-1229-3.
21. Kienle GS, Grugel R, Kiene H. Safety of higher dosages of Viscum album L. in animals and humans – systematic review of immune changes and safety parameters. BMC Complement Altern Med. 2011;11:72. doi:10.1186/1472-6882-11-72.
22. Kim BK, Choi MJ, Park KY, Cho EJ. Protective effects of Korean mistletoe lectin on radical-induced oxidative stress. Biol Pharm Bull. 2010;33:1152–1158. doi: 10.1248/bpb.33.1152.
23. Kim SY, Yang EJ, Son YK, Yeo JH, Song KS. Enhanced anti-oxidative effect of fermented Korean mistletoe is originated from an increase in the contents of caffeic acid and lyoniresinol. Food Funct. 2016;7(5):2270-2277. doi:10.1039/c6fo00138f.
24. Kusi M, Shrestha K, Malla R. Study on phytochemical, antibacterial, antioxidant and toxicity profile of Viscum album Linn associated with Acacia catechu. Nepal J Biotechnol. 2015;3:60–65. doi: 10.3126/njb.v3i1.14234.
25. Lee JY, Kim JY, Lee YG, Byeon SE, Kim BH, Rhee MH, Lee A, Kwon M, Hong S, Cho JY. In vitroimmunoregulatory effects of Korean mistletoe lectin on functional activation of monocytic and macrophage-like cells. Biol Pharm Bull. 2007;30(11):2043-2051. doi:10.1248/bpb.30.2043.
26. Lev E, Ephraim M, Ben-Arye E. European and Oriental mistletoe: from mythology to contemporary integrative cancer care. Eur J Integr Med. 2011;3:e133–e137. doi: 10.1016/J.EUJIM.2011.05.052.
27. Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, Ahn BW, Shaltiel S, Stadtman ER. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol. 1990;186:464-478. doi:10.1016/0076-6879(90)86141-h.
28. Levine RL. Carbonyl modified proteins in cellular regulation, aging, and disease. Free RadicBiol Med. 2002;32(9):790-796. doi:10.1016/s0891-5849(02)00765-7.
29. Luo J, le Cessie S, van Heemst D, Noordam R. Diet-Derived Circulating Antioxidants and Risk of Coronary Heart Disease: A Mendelian Randomization Study. J Am CollCardiol. 2021;77(1):45-54. doi:10.1016/j.jacc.2020.10.048.
30. Mistletoe. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; July 25, 2022.
31. Mojiminiyi FBO, Owolabi ME, Igbokwe UV, Ajagbonna OP. The vasorelaxant effect of Viscum album leaf extract is mediated by calcium-dependent mechanism. Niger J Physiol Sci. 2008;23:115–120. doi: 10.4314/njps.v23i1-2.54947.
32. Nazaruk J, Orlikowski P. Phytochemical profile and therapeutic potential of Viscum album L. Nat Prod Res. 2016;30(4):373-385. doi:10.1080/14786419.2015.1022776.
33. Nicoletti M. The Anti-Inflammatory Activity of Viscum album. Plants (Basel). 2023;12(7):1460. doi:10.3390/plants12071460.
34. Obi RK, Shenge JA. In vitro antiviral activities of Bryophyllumpinnatum (Odaaopuo) and Viscum album (Awuruse). Res J Microbiol. 2018;13:138–146. doi: 10.3923/jm.2018.138.146.
35. Oei SL, Thronicke A, Kröz M, Matthes H, Schad F. Use and Safety of Viscum album L Applications in Cancer Patients With Preexisting Autoimmune Diseases: Findings From the Network Oncology Study. Integr Cancer Ther. 2019;18:1534735419832367. doi:10.1177/1534735419832367.
36. Ofem OE, Eno AE, Imoru J, Nkanu E, Unoh F, Ibu JO. Effect of crude aqueous leaf extract of Viscum album (mistletoe) in hypertensive rats. Indian J Pharmacol. 2007;39:15–19. doi: 10.4103/0253-7613.30756.
37. Onay-Uçar E, Karagöz A, Arda N. Antioxidant activity of Viscum album ssp. album. Fitoterapia. 2006;77(7-8):556-560. doi:10.1016/j.fitote.2006.08.001.
38. Orhan DD, Senol FS, Hosbas S, Orhan IE. Assessment of cholinesterase and tyrosinase inhibitory and antioxidant properties of Viscum album L. samples collected from different host plants and its two principal substances. Ind Crops Prod. 2014;62:341–349. doi: 10.1016/J.INDCROP.2014.08.044.
39. Papuc C, Crivineanu M, Goran G, Nicorescu V, Durdun N. Free radicals scavenging and antioxidant activity of European mistletoe (Viscum album) and European Birthwort (Aristolochiaclematitis). Rev Chim. 2010;61:619-622.
40. Park KH, Choi SH. The effect of mistletoe, Viscum album coloratum, extract on innate immune response of Nile tilapia (Oreochromisniloticus). Fish Shellfish Immunol. 2012;32(6):1016-1021. doi:10.1016/j.fsi.2012.02.023.
41. Pietrzak W, Nowak R, Gawlik-Dziki U, Lemieszek MK, Rzeski W. LC-ESI-MS/MS identification of biologically active phenolic compounds in mistletoe berry extracts from different host trees. Molecules. 2017;22:1–15. doi: 10.3390/molecules22040624.
42. Popova OI. Phenolic compouns of Viscum album. Chem Nat Compd. 1991;27:123. doi: 10.1007/BF00629850.
43. Poprac P, Jomova K, Simunkova M, Kollar V, Rhodes CJ, Valko M. Targeting Free Radicals in Oxidative Stress-Related Human Diseases. Trends Pharmacol Sci. 2017;38(7):592-607. doi:10.1016/j.tips.2017.04.005.
44. Poruthukaren KJ, Palatty PL, Baliga MS, Suresh S. Clinical evaluation of Viscum album mother tincture as an antihypertensive: a pilot study. J Evid Based Complementary Altern Med. 2014;19(1):31-35. doi:10.1177/2156587213507726.
45. Radenkovic M, Ivetic V, Popovic M, Brankovic S, Gvozdenovic L. Effects of mistletoe (Viscum album L., Loranthaceae) extracts on arterial blood pressure in rats treated with atropine sulfate and hexocycline. ClinExpHypertens. 2009;31:11–19. doi: 10.1080/10641960802409820.
46. Schaller G, Urech K, Grazi G, Giannattasio M. Viscotoxin composition of the three European subspecies of Viscum album. Planta Med. 1998;64(7):677-678. doi:10.1055/s-2006-957553.
47. Sengul M, Yildiz H, Gungor N, Cetin B, Eser Z, Ercisli S. Total phenolic content, antioxidant and antimicrobial activities of some medicinal plants. Pak J Pharm Sci. 2009;22:102-106.
48. Stadtman ER. Protein oxidation in aging and age-related diseases. Ann N Y Acad Sci. 2001;928:22-38. doi:10.1111/j.1749-6632.2001.tb05632.x.
49. Suveren E, Baxter GF, Iskit AB, Turker AU. Cardioprotective effects of Viscum album L. subsp. album (European misletoe) leaf extracts in myocardial ischemia and reperfusion. J Ethnopharmacol. 2017;209:203–209. doi: 10.1016/J.JEP.2017.07.010.
50. Szurpnicka A, Kowalczuk A, Szterk A. Biological activity of mistletoe: in vitro and in vivo studies and mechanisms of action. Arch Pharm Res. 2020;43(6):593-629. doi:10.1007/s12272-020-01247-w.
51. Szurpnicka A, Zjawiony JK, Szterk A. Therapeutic potential of mistletoe in CNS-related neurological disorders and the chemical composition of Viscum species. J Ethnopharmacol. 2019;231:241-252. doi:10.1016/j.jep.2018.11.025.
52. Tenorio FA, del Valle L, González A, Pastelín G. Vasodilator activity of the aqueous extract of Viscum album. Fitoterapia. 2005;76:204–209. doi: 10.1016/J.FITOTE.2004.12.013.
53. Tenorio-Lopez FA, Del Valle ML, Olvera GZ, Narvaez JCT, Pastelin G. Viscum album aqueous extract induces NOS-2 and NOS-3 overexpression in Guinea pig hearts. Nat Prod Res. 2006;20:1176–1182. doi: 10.1080/14786410600898979.
54. Tibe O, Sutherland IA, Lesperance L, Harding DR. The effect of purified condensed tannins of forage plants from Botswana on the free-living stages of gastrointestinal nematode parasites of livestock. Vet Parasitol. 2013;197(1-2):160-167. doi:10.1016/j.vetpar.2013.07.004.
55. Turker AU, Yildirim AB, Karakas FP. Antitumor and antibacterial activities of Viscum album L. grown on different host trees. Spat DD. 2012;2:229–236. doi: 10.5455/spatula.20121224052924.
56. Urech K, Baumgartner S. Chemical Constituents of Viscum album L.: Implications for the Pharmaceutical Preparation of Mistletoe, Mistletoe: From Mythology to Evidence-Based Medicine. Transl Res Biomed. 2015;4:11–23. doi: 10.1159/000375422.
57. Wrotek S, Skawiński R, Kozak W. Immunostymulujące właściwości preparatów pozyskiwanych z jemioły i ich zastosowanie w onkologii [Immunostimulatoryproperties of mistletoeextracts and theirapplication in oncology]. PostepyHig Med Dosw (Online). 2014;68:1216-1224. doi:10.5604/17322693.1126850.
58. Yoo JM, Park KI, Ma JY. Anticolitic Effect of Viscumcoloratum through Suppression of Mast Cell Activation. Am J Chin Med. 2019;47(1):203-221. doi:10.1142/S0192415X19500101.
59. Yoo JM, Yang JH, Kim YS, Yang HJ, Cho WK, Ma JY. Inhibitory Effects of Viscumcoloratum Extract on IgE/Antigen-Activated Mast Cells and Mast Cell-Derived Inflammatory Mediator-Activated Chondrocytes. Molecules. 2016;22(1):37. doi:10.3390/molecules22010037.
60. Yoon TJ, Yoo YC, Kang TB, Shimazaki K, Song SK, Lee KH, Kim SH, Park CH, Azuma I, Kim JB. Lectins isolated from Korean mistletoe (Viscum album coloratum) induce apoptosis in tumor cells. Cancer Lett. 1999;136(1):33-40. doi:10.1016/s0304-3835(98)00300-0.
61. Zar JH. Biostatistical Analysis. 4th ed., Prentice-Hall Inc., Englewood Cliffs, New Jersey, 1999.
62. Zheng Y, Zhang L, Qiu Z, Yu Z, Shi W, Wang X. Comparison of oxidation extent, structural characteristics, and oxidation sites of myofibrillar protein affected by hydroxyl radicals and lipid-oxidizing system. Food Chem. 2022;396:133710. doi:10.1016/j.foodchem.2022.133710.
63. Zuber D. Biological flora of Central Europe: Viscum album L. Flora MorpholDistribFunctEcol Plants. 2004;199(3):181–203. doi: 10.1078/0367-2530-00147.
2. Bartosz G. Total antioxidant capacity. AdvClin Chem. 2003;37:219-292. doi:10.1016/s0065-2423(03)37010-6.
3. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248-254. doi:10.1006/abio.1976.9999.
4. Braedel-Ruoff S. Immunomodulatory effects of Viscum album extracts on natural killer cells: review of clinical trials. ForschKomplementmed. 2010;17(2):63-73. doi:10.1159/000288702.
5. Bussing A. Mistletoe. The genus Viscum. Amsterdam: Hardwood Academic Publishers; 2000.
6. Choi SH, Park KH, Yoon TJ, Kim JB, Jang YS, Choe CH. Dietary Korean mistletoe enhances cellular non-specific immune responses and survival of Japanese eel (Anguilla japonica). Fish Shellfish Immunol. 2008;24(1):67-73. doi:10.1016/j.fsi.2007.08.007.
7. Dubinina EE, Burmistrov SO, Khodov DA, Porotov IG. Okislitel'naiamodifikatsiiabelkovsyvorotkikrovicheloveka, metodeeopredeleniia [Oxidative modification of human serum proteins. A method of determining it]. Vopr Med Khim. 1995;41(1):24-26.
8. Dügenci SK, Arda N, Candan A. Some medicinal plants as immunostimulant for fish. J Ethnopharmacol. 2003;88(1):99-106. doi:10.1016/s0378-8741(03)00182-x.
9. Fukunaga T, Kajikawa I, Nishiya K, Watanabe Y, Suzuki N, Takeya K, Itokawa H. Studies on the constituents of the European mistletoe, Viscum album L. II Chem Pharm Bull. 1988;36(3):1185–1189. doi: 10.1248/cpb.36.1185.
10. Galaktionova LP, Molchanov AV, El'chaninova SA, VarshavskiĭBIa. Sostoianieperekisnogookisleniia u bol'nykh s iazvennoĭbolezn'iuzheludkaidvenadtsatiperstnoĭkishki [Lipid peroxidation in patients with gastric and duodenal peptic ulcers]. Klin Lab Diagn. 1998;(6):10-14.
11. Garg S, Patil UK, Shrivastava TP. Wound healing potential of ViscumArticulumBrm., an ethnomedical plant of Sikkim on rat. Int J Res PhytochemPharmacol. 2012;2:138–142. doi: 10.1186/s13002-017-0148-9.
12. Geetha KM, Murugan V, Pavan Kumar P, Wilson B. Antiepileptic activity of ViscumarticulatumBurm and its isolated bioactive compound in experimentally induced convulsions in rats and mice. Eur J Biomed Pharm Sci. 2018;5:311–318.
13. Grossarth-Maticek R, Kiene H, Baumgartner SM, Ziegler R. Use of Iscador, an extract of European mistletoe (Viscum album), in cancer treatment: prospective nonrandomized and randomized matched-pair studies nested within a cohort study. AlternTher Health Med. 2001;7(3).
14. Gupta G, Kazmi I, Afzal M, Rahman M, Saleem S, Ashraf S, Khusroo MJ, Nazeer K, Ahmed S, Mujeeb M, Ahmed Z, Anwar F. Sedative, antiepileptic and antipsychotic effects of Viscum album L. (Loranthaceae) in mice and rats. J Ethnopharmacol. 2012;141:810–816. doi: 10.1016/j.jep.2012.03.013.
15. Holandino C, Melo MNO, Oliveira AP, Batista JVDC, Capella MAM, Garrett R, Grazi M, Ramm H, Torre CD, Schaller G, Urech K, Weissenstein U, Baumgartner S. Phytochemical analysis and in vitro anti-proliferative activity of Viscum album ethanolic extracts. BMC Complement Med Ther. 2020;20(1):215. doi:10.1186/s12906-020-02987-4.
16. Hussain MA, Khan MQ, Hussain N, Habib T. Antibacterial and antifungal potential of leaves and twigs of Viscum album L. J Med Plants Res. 2011;5:5545–5549.
17. Kamyshnikov VS. A reference work for clinical and biochemical research and laboratory diagnostics. MEDpress-inform, Moscow, 2004.
18. Karagöz A, Kesici S, Vural A, Usta M, Tezcan B, Semerci T, Teker E. Cardioprotective effects of Viscum album L. ssp. album (Loranthaceae) on isoproterenol-induced heart failure via regulation of the nitric oxide pathway in rats. Anatol J Cardiol. 2016;16:923–930. doi: 10.14744/AnatolJCardiol.2016.6780.
19. Karagöz A, Önay E, Arda N, Kuru A. Antiviral potency of mistletoe (Viscum album ssp. album) extracts against human parainfluenza virus type 2 in Vero cells. Phyther Res. 2003;17:560–562. doi: 10.1002/ptr.1163.
20. Khan T, Ali S, Qayyum R, Hussain I, Wahid F, Shah AJ. Intestinal and vascular smooth muscle relaxant effect of Viscum album explains its medicinal use in hyperactive gut disorders and hypertension. BMC Complement Aternative Med. 2016;16:251. doi: 10.1186/s12906-016-1229-3.
21. Kienle GS, Grugel R, Kiene H. Safety of higher dosages of Viscum album L. in animals and humans – systematic review of immune changes and safety parameters. BMC Complement Altern Med. 2011;11:72. doi:10.1186/1472-6882-11-72.
22. Kim BK, Choi MJ, Park KY, Cho EJ. Protective effects of Korean mistletoe lectin on radical-induced oxidative stress. Biol Pharm Bull. 2010;33:1152–1158. doi: 10.1248/bpb.33.1152.
23. Kim SY, Yang EJ, Son YK, Yeo JH, Song KS. Enhanced anti-oxidative effect of fermented Korean mistletoe is originated from an increase in the contents of caffeic acid and lyoniresinol. Food Funct. 2016;7(5):2270-2277. doi:10.1039/c6fo00138f.
24. Kusi M, Shrestha K, Malla R. Study on phytochemical, antibacterial, antioxidant and toxicity profile of Viscum album Linn associated with Acacia catechu. Nepal J Biotechnol. 2015;3:60–65. doi: 10.3126/njb.v3i1.14234.
25. Lee JY, Kim JY, Lee YG, Byeon SE, Kim BH, Rhee MH, Lee A, Kwon M, Hong S, Cho JY. In vitroimmunoregulatory effects of Korean mistletoe lectin on functional activation of monocytic and macrophage-like cells. Biol Pharm Bull. 2007;30(11):2043-2051. doi:10.1248/bpb.30.2043.
26. Lev E, Ephraim M, Ben-Arye E. European and Oriental mistletoe: from mythology to contemporary integrative cancer care. Eur J Integr Med. 2011;3:e133–e137. doi: 10.1016/J.EUJIM.2011.05.052.
27. Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, Ahn BW, Shaltiel S, Stadtman ER. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol. 1990;186:464-478. doi:10.1016/0076-6879(90)86141-h.
28. Levine RL. Carbonyl modified proteins in cellular regulation, aging, and disease. Free RadicBiol Med. 2002;32(9):790-796. doi:10.1016/s0891-5849(02)00765-7.
29. Luo J, le Cessie S, van Heemst D, Noordam R. Diet-Derived Circulating Antioxidants and Risk of Coronary Heart Disease: A Mendelian Randomization Study. J Am CollCardiol. 2021;77(1):45-54. doi:10.1016/j.jacc.2020.10.048.
30. Mistletoe. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; July 25, 2022.
31. Mojiminiyi FBO, Owolabi ME, Igbokwe UV, Ajagbonna OP. The vasorelaxant effect of Viscum album leaf extract is mediated by calcium-dependent mechanism. Niger J Physiol Sci. 2008;23:115–120. doi: 10.4314/njps.v23i1-2.54947.
32. Nazaruk J, Orlikowski P. Phytochemical profile and therapeutic potential of Viscum album L. Nat Prod Res. 2016;30(4):373-385. doi:10.1080/14786419.2015.1022776.
33. Nicoletti M. The Anti-Inflammatory Activity of Viscum album. Plants (Basel). 2023;12(7):1460. doi:10.3390/plants12071460.
34. Obi RK, Shenge JA. In vitro antiviral activities of Bryophyllumpinnatum (Odaaopuo) and Viscum album (Awuruse). Res J Microbiol. 2018;13:138–146. doi: 10.3923/jm.2018.138.146.
35. Oei SL, Thronicke A, Kröz M, Matthes H, Schad F. Use and Safety of Viscum album L Applications in Cancer Patients With Preexisting Autoimmune Diseases: Findings From the Network Oncology Study. Integr Cancer Ther. 2019;18:1534735419832367. doi:10.1177/1534735419832367.
36. Ofem OE, Eno AE, Imoru J, Nkanu E, Unoh F, Ibu JO. Effect of crude aqueous leaf extract of Viscum album (mistletoe) in hypertensive rats. Indian J Pharmacol. 2007;39:15–19. doi: 10.4103/0253-7613.30756.
37. Onay-Uçar E, Karagöz A, Arda N. Antioxidant activity of Viscum album ssp. album. Fitoterapia. 2006;77(7-8):556-560. doi:10.1016/j.fitote.2006.08.001.
38. Orhan DD, Senol FS, Hosbas S, Orhan IE. Assessment of cholinesterase and tyrosinase inhibitory and antioxidant properties of Viscum album L. samples collected from different host plants and its two principal substances. Ind Crops Prod. 2014;62:341–349. doi: 10.1016/J.INDCROP.2014.08.044.
39. Papuc C, Crivineanu M, Goran G, Nicorescu V, Durdun N. Free radicals scavenging and antioxidant activity of European mistletoe (Viscum album) and European Birthwort (Aristolochiaclematitis). Rev Chim. 2010;61:619-622.
40. Park KH, Choi SH. The effect of mistletoe, Viscum album coloratum, extract on innate immune response of Nile tilapia (Oreochromisniloticus). Fish Shellfish Immunol. 2012;32(6):1016-1021. doi:10.1016/j.fsi.2012.02.023.
41. Pietrzak W, Nowak R, Gawlik-Dziki U, Lemieszek MK, Rzeski W. LC-ESI-MS/MS identification of biologically active phenolic compounds in mistletoe berry extracts from different host trees. Molecules. 2017;22:1–15. doi: 10.3390/molecules22040624.
42. Popova OI. Phenolic compouns of Viscum album. Chem Nat Compd. 1991;27:123. doi: 10.1007/BF00629850.
43. Poprac P, Jomova K, Simunkova M, Kollar V, Rhodes CJ, Valko M. Targeting Free Radicals in Oxidative Stress-Related Human Diseases. Trends Pharmacol Sci. 2017;38(7):592-607. doi:10.1016/j.tips.2017.04.005.
44. Poruthukaren KJ, Palatty PL, Baliga MS, Suresh S. Clinical evaluation of Viscum album mother tincture as an antihypertensive: a pilot study. J Evid Based Complementary Altern Med. 2014;19(1):31-35. doi:10.1177/2156587213507726.
45. Radenkovic M, Ivetic V, Popovic M, Brankovic S, Gvozdenovic L. Effects of mistletoe (Viscum album L., Loranthaceae) extracts on arterial blood pressure in rats treated with atropine sulfate and hexocycline. ClinExpHypertens. 2009;31:11–19. doi: 10.1080/10641960802409820.
46. Schaller G, Urech K, Grazi G, Giannattasio M. Viscotoxin composition of the three European subspecies of Viscum album. Planta Med. 1998;64(7):677-678. doi:10.1055/s-2006-957553.
47. Sengul M, Yildiz H, Gungor N, Cetin B, Eser Z, Ercisli S. Total phenolic content, antioxidant and antimicrobial activities of some medicinal plants. Pak J Pharm Sci. 2009;22:102-106.
48. Stadtman ER. Protein oxidation in aging and age-related diseases. Ann N Y Acad Sci. 2001;928:22-38. doi:10.1111/j.1749-6632.2001.tb05632.x.
49. Suveren E, Baxter GF, Iskit AB, Turker AU. Cardioprotective effects of Viscum album L. subsp. album (European misletoe) leaf extracts in myocardial ischemia and reperfusion. J Ethnopharmacol. 2017;209:203–209. doi: 10.1016/J.JEP.2017.07.010.
50. Szurpnicka A, Kowalczuk A, Szterk A. Biological activity of mistletoe: in vitro and in vivo studies and mechanisms of action. Arch Pharm Res. 2020;43(6):593-629. doi:10.1007/s12272-020-01247-w.
51. Szurpnicka A, Zjawiony JK, Szterk A. Therapeutic potential of mistletoe in CNS-related neurological disorders and the chemical composition of Viscum species. J Ethnopharmacol. 2019;231:241-252. doi:10.1016/j.jep.2018.11.025.
52. Tenorio FA, del Valle L, González A, Pastelín G. Vasodilator activity of the aqueous extract of Viscum album. Fitoterapia. 2005;76:204–209. doi: 10.1016/J.FITOTE.2004.12.013.
53. Tenorio-Lopez FA, Del Valle ML, Olvera GZ, Narvaez JCT, Pastelin G. Viscum album aqueous extract induces NOS-2 and NOS-3 overexpression in Guinea pig hearts. Nat Prod Res. 2006;20:1176–1182. doi: 10.1080/14786410600898979.
54. Tibe O, Sutherland IA, Lesperance L, Harding DR. The effect of purified condensed tannins of forage plants from Botswana on the free-living stages of gastrointestinal nematode parasites of livestock. Vet Parasitol. 2013;197(1-2):160-167. doi:10.1016/j.vetpar.2013.07.004.
55. Turker AU, Yildirim AB, Karakas FP. Antitumor and antibacterial activities of Viscum album L. grown on different host trees. Spat DD. 2012;2:229–236. doi: 10.5455/spatula.20121224052924.
56. Urech K, Baumgartner S. Chemical Constituents of Viscum album L.: Implications for the Pharmaceutical Preparation of Mistletoe, Mistletoe: From Mythology to Evidence-Based Medicine. Transl Res Biomed. 2015;4:11–23. doi: 10.1159/000375422.
57. Wrotek S, Skawiński R, Kozak W. Immunostymulujące właściwości preparatów pozyskiwanych z jemioły i ich zastosowanie w onkologii [Immunostimulatoryproperties of mistletoeextracts and theirapplication in oncology]. PostepyHig Med Dosw (Online). 2014;68:1216-1224. doi:10.5604/17322693.1126850.
58. Yoo JM, Park KI, Ma JY. Anticolitic Effect of Viscumcoloratum through Suppression of Mast Cell Activation. Am J Chin Med. 2019;47(1):203-221. doi:10.1142/S0192415X19500101.
59. Yoo JM, Yang JH, Kim YS, Yang HJ, Cho WK, Ma JY. Inhibitory Effects of Viscumcoloratum Extract on IgE/Antigen-Activated Mast Cells and Mast Cell-Derived Inflammatory Mediator-Activated Chondrocytes. Molecules. 2016;22(1):37. doi:10.3390/molecules22010037.
60. Yoon TJ, Yoo YC, Kang TB, Shimazaki K, Song SK, Lee KH, Kim SH, Park CH, Azuma I, Kim JB. Lectins isolated from Korean mistletoe (Viscum album coloratum) induce apoptosis in tumor cells. Cancer Lett. 1999;136(1):33-40. doi:10.1016/s0304-3835(98)00300-0.
61. Zar JH. Biostatistical Analysis. 4th ed., Prentice-Hall Inc., Englewood Cliffs, New Jersey, 1999.
62. Zheng Y, Zhang L, Qiu Z, Yu Z, Shi W, Wang X. Comparison of oxidation extent, structural characteristics, and oxidation sites of myofibrillar protein affected by hydroxyl radicals and lipid-oxidizing system. Food Chem. 2022;396:133710. doi:10.1016/j.foodchem.2022.133710.
63. Zuber D. Biological flora of Central Europe: Viscum album L. Flora MorpholDistribFunctEcol Plants. 2004;199(3):181–203. doi: 10.1078/0367-2530-00147.