Evaluation of toxicity and antioxidative effects of Tussilago farfara and Verbascum thapsus water extracts in zebrafish and in bronchial epithelial cells
Keywords:Tussilago farfara (coltsfoot), Verbascum thapsus (mullein), BEAS 2B cells, zebrafish, asthma treatment
- T. farfara and V. thapsus have long been used as natural supplements for treating respiratory disorders.
- This is the first study to investigate the toxicity of T. farfara and V. thapsus extracts in zebrafish and their anti-oxidative properties in cell culture. V. thapsus extract showed toxic effects on zebrafish embryos and BEAS 2B epithelial bronchial cells. T. farfara extract exerted a protective effect on the cells after induction of oxidative stress.
- Our findings further elucidate the function of T. farfara as a natural medicine for treating respiratory disorders through its potential anti-oxidative effects on epithelial bronchial cells.
Abstract: Tussilago farfara (coltsfoot) and Verbascum thapsus (mullein) have been used as folk remedies for treating respiratory disorders. The aim of this study was to test the toxicity of the water extracts of T. farfara and V. thapsus in vivo in zebrafish and in vitro in BEAS 2B epithelial bronchial cells. To the best of our knowledge, this is the first study to investigate the antioxidative properties of T. farfara and V. thapsus extracts in cell culture. Our results show that the T. farfara leaf extract does not produce toxic effects on zebrafish embryos or BEAS 2B cells, and that it has a protective effect in BEAS 2B after induction of oxidative stress. The water extract from V. thapsus displayed pronounced toxic effects on zebrafish embryos and BEAS 2B cells and did not exhibit a significant antioxidative effect on BEAS 2B cells exposed to oxidative stress. Our results suggest that the use of T. farfara water leaf extract is potentially safe and effective in treating respiratory disorders, whereas the use of V. thapsus needs further investigation.
Received: December 13, 2018; Revised: March 1, 2019; Accepted: March 26, 2019; Published online: April 4, 2019
How to cite this article: Dragičević S, Kovačević D, Divac Rankov A, Nikolić A, Radojković D, Radović S. Evaluation of toxicity and antioxidative effects of Tussilago farfara and Verbascum thapsus water extracts in zebrafish and in bronchial epithelial cells. Arch Biol Sci. 2019;71(3):409-16.
Lee KH. Research and future trends in the pharmaceutical development of medicinal herbs from Chinese medicine. Public Health Nutr. 2000;3(4A):515-22.
World Health Organization. WHO guidelines on safety monitoring of herbal medicines in pharmacovigilance systems. Geneva: World Health Organization; 2004. 82 p.
Grieve M. A modern herbal. New York: Dover Publications; 1981. 902 p.
Uzun E, Sariyar G, Adsersen A, Karakoc B, Otük G, Oktayoglu E, Pirildar S. Traditional medicine in Sakarya province (Turkey) and antimicrobial activities of selected species. J Ethnopharmacol. 2004;95(2-3):287-96.
Kim MR, Lee JY, Lee HH, Aryal DK, Kim YG, Kim SK, Woo ER, Kang KW. Antioxidative effects of quercetin-glycosides isolated from the flower buds of Tussilago farfara L. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2006;44(8):1299-307.
Turker AU, Gurel E. Common mullein (Verbascum thapsus L.): recent advances in research. Phytother Res. 2005;19(9):733-9.
Escobar FM, Sabini MC, Zanon SM, Tonn CE, Sabini LI. Antiviral effect and mode of action of methanolic extract of Verbascum thapsus L. on pseudorabies virus (strain RC/79). Nat Prod Res. 2012;26(17):1621-5.
Kogje K, Jagdale V, Dudhe S, Phanikumar G, Badere R. Antioxidant property and phenolic compounds of few important plants from trans-himalayan regions of north India. Journal of Herbal Medicine and Toxicology. 2010;4(2):145-51.
Pal H, Kumar T, Karki H. In vitro antioxidant and renoprotective potential of methanolic extract of Verbascum thapsus leaf in rats. Der Pharmacia Sinica. 2013;4(1):113-22.
Narayanaswamy N, Balakrishnan KP. Evaluation of some Medicinal Plants for their Antioxidant Properties. Int J Pharm Tech Res. 2011;3:381–385.
Riaz M, Zia-Ul-Haq M, Jaafar HZE. Common mullein, pharmacological and chemical aspects. Braz J Pharmacogn. 2013;23(6):948-59.
Bhattacharya S. Reactive Oxygen Species and Cellular Defense System. In: Rani V, Yadav U, editors. Free Radicals in Human Health and Disease. New Delhi: Springer New Delhi; 2015. p. 17-29.
van der Toorn M, Smit-de Vries MP, Slebos DJ, de Bruin HG, Abello N, van Oosterhout AJ, Bischoff R, Kauffman HF. Cigarette smoke irreversibly modifies glutathione in airway epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2007;293(5):L1156-62.
Forman HJ, Torres M, Fukuto J. Redox signaling. Mol Cell Biochem. 2002;234-235(1-2):49-62.
Cross CE, Valacchi G, Schock B, Wilson M, Weber S, Eiserich J, van der Vliet A. Environmental oxidant pollutant effects on biologic systems: a focus on micronutrient antioxidant-oxidant interactions. Am J Respir Crit Care Med. 2002;166(12 Pt 2):S44-50.
Christofidou-Solomidou M, Muzykantov VR. Antioxidant strategies in respiratory medicine. Treat Respir Med. 2006;5(1):47-78.
Kinnula VL, Crapo JD. Superoxide dismutases in the lung and human lung diseases. Am J Respir Crit Care Med. 2003;167(12):1600-19.
Westerfield M. The zebrafish book: a guide for the laboratory use of zebrafish (Danio rerio). 4th ed. [Interent] Eugene: Institute of Neuroscience, University of Oregon; 2000. [cited 2018 Dec 1] Available from: https://zfin.org/zf_info/zfbook/zfbk.html
Organisation for Economic Co-operation and Development. Test No. 236: Fish Embryo Acute Toxicity (FET) test OECD Guidelines for the Testing of Chemicals; Section 2) [Interent]. Paris: OECD Publishing; 2013. [cited 2018 Dec 1] 22 p. Available from: https://www.oecd-ilibrary.org/environment/test-no-236-fish-embryo-acute-toxicity-fet-test_9789264203709-en
Patel S, Gheewala N, Suthar A, Patel S. In vitro Cytotoxicity Activity of Solanum nigrum Extracts Agains HELA Cell Line and VERO Cell Line. Int J Pharm Pharm Sci. 2009;1(1):38-46.
Wages PA, Silbajoris R, Speen A, Brighton L, Henriquez A, Tong H, Bromberg PA, Simmons SO, Samet JM. Role of H2O2 in the oxidative effects of zinc exposure in human airway epithelial cells. Redox Biol. 2014;3:47-55.
Kokoska L, Polesny Z, Rada V, Nepovim A, Vanek T. Screening of some Siberian medicinal plants for antimicrobial activity. J Ethnopharmacol. 2002;82(1):51-3.
Zhang L, Ravipati AS, Koyyalamudi SR, Jeong SC, Reddy N, Bartlett J, Smith PT, Shanmugam K, Münch G, Wu MJ, Satyanarayanan M, Vysetti B. Anti-fungal and anti-bacterial activities of ethanol extracts of selected traditional Chinese medicinal herbs. Asian Pac J Trop Med. 2013;6(9):673-81.
Song FL, Gan RY, Zhang Y, Xiao Q, Kuang L, Li HB. Total phenolic contents and antioxidant capacities of selected chinese medicinal plants. Int J Mol Sci. 2010;11(6):2362-72.
Dobravalskyte D, Petras Rimantas Venskutonis P, Talou T, Zebib B, Merah O, Ragažinskienė O. Antioxidant Properties and Composition of Deodorized Extracts of Tussilago farfara L. Rec Nat Prod. 2013;7(3):201-9.
Li CT, Liu YP, He FC, Li Y. In vitro antioxidant activities of Tussilago farfara, a new record species to Chanbai Mountain. Chin J Nat Med. 2012;10(4):260-2.
Lee HJ, Cho HS, Jun SY, Lee JJ, Yoon JY, Lee JH, Song HH, Choi SH, Kim SY, Saloura V, Park CG, Kim NS. Tussilago farfara L. augments TRAIL-induced apoptosis through MKK7/JNK activation by inhibition of MKK7‑TIPRL in human hepatocellular carcinoma cells. Oncol Rep. 2014;32(3):1117-23.
Cho J, Kim HM, Ryu JH, Jeong YS, Lee YS, Jin C. Neuroprotective and antioxidant effects of the ethyl acetate fraction prepared from Tussilago farfara L. Biol Pharm Bull. 2005;28(3):455-60.
Lin LT, Liu LT, Chiang LC, Lin CC. In vitro anti-hepatoma activity of fifteen natural medicines from Canada. Phytother Res. 2002;16(5):440-4.
Zhao YL, Wang SF, Li Y, He QX, Liu KC, Yang YP, Li XL. Isolation of chemical constituents from the aerial parts of Verbascum thapsus and their antiangiogenic and antiproliferative activities. Arch Pharm Res. 2011;34(5):703-7.
Ryu JH, Jeong YS, Sohn DH. A new bisabolene epoxide from Tussilago farfara, and inhibition of nitric oxide synthesis in LPS-activated macrophages. J Nat Prod. 1999;62(10):1437-8.
Ravipati AS, Zhang L, Koyyalamudi SR, Jeong SC, Reddy N, Bartlett J, Smith PT, Shanmugam K, Münch G, Wu MJ, Satyanarayanan M, Vysetti B. Antioxidant and anti-inflammatory activities of selected Chinese medicinal plants and their relation with antioxidant content. BMC Complement Altern Med. 2012;12:173.
Kang U, Park J, Han AR, Woo MH, Lee JH, Lee SK, Chang TS, Woo HA, Seo EK. Identification of cytoprotective constituents of the flower buds of Tussilago farfara against glucose oxidase-induced oxidative stress in mouse fibroblast NIH3T3 cells and human keratinocyte HaCaT cells. Arch Pharm Res. 2016;39(4):474-80.
Chanaj-Kaczmarek J, Wojcinska M, Matlawska I. Phenolics in the Tussilago farfara leaves. Herba Polonica. 2013;59(1):35-43.