Research Article

Tussilago farfara Extracts Decrease Lung Injury in Fine Dust-Induced Mice by Inhibiting of Inflammatory Cytokine Levels, Neutrophil Accumulation, and Endothelial Dysfunction

Mi-Young Yun, Won-Jin Baek and Hwa-Jung Choi*

Published: 30 May, 2024 | Volume 8 - Issue 1 | Pages: 067-074

Fine Dust (FD) in the respiratory air generates a variety of human disease issues throughout the earth. This study aimed to investigate whether (1) Tussilago farfara extracts (TF) decrease neutrophils accumulation, typical pathological features, and goblet cell hyperplasia in mice following exposure to fine dust (FD); (2) inflammatory cytokines result from FD exposure; and (3) asymmetric dimethyl-arginine (ADMA) and symmetric dimethyl-arginine (SDMA) levels in the mice following exposure to FD. Seven-week-old male Balb/c mice (n = 5/group) were instilled two times by intra-nasal-trachea (INT) injection for 3 days and 6 days to the mice four groups; normal, control, FD + dexamethasone (Dexa, positive control), and FD + TF groups. TF suspended in 0.5% carboxymethyl cellulose (CMC) was administered orally to the mice daily for 10 days (100 mg/kg). Neutrophil accumulation, typical pathological features, goblet cell hyperplasia, ADMA, and SDMA levels were assessed on day 10 in FD-induced mice. Results indicated FD significantly reduced neutrophil accumulation in BALF, typical pathological features containing goblet cell hyperplasia in lung tissues, and inflammatory cytokines [interleukin (IL)-17 and tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-2 (MIP-2) and C-X-C motif chemokine 1 (CXCL-1)]. Furthermore, TF significantly decreased levels of elevated ADMA and SDMA by FD exposure. Collectively, TF decreased the counts of neutrophils in BALF, histological changes in lung tissues due to downstream secretion of inflammatory cytokines, and levels of ADMA and SDMA. Therefore, TF may be a potential therapeutics for treating FD-associated diseases.

Read Full Article HTML DOI: 10.29328/journal.apps.1001058 Cite this Article Read Full Article PDF


Tussilago farfara extracts; Fine Dust (FD); Neutrophils accumulation; Pathological features; Inflammatory cytokines; Lung tissues


  1. Vanicela BD, Nebel M, Stephan M, Riethmüller C, Gresser GT. Quantitative analysis of fine dust particles on moss surfaces under laboratory conditions using the example of Brachythecium rutabulum. Environ Sci Pollut Res Int. 2021 Oct; 28(37):51763-51771. doi: 10.1007/s11356-021-14218-5. Epub 2021 May 15. PMID: 33991303; PMCID: PMC8458176.
  2. Shiwakoti S, Adhikari D, Lee JP, Kang KW, Lee IS, Kim HJ, Oak MH. Prevention of Fine Dust-Induced Vascular Senescence by Humulus lupulusExtract and Its Major Bioactive Compounds. Antioxidants (Basel). 2020 Dec 7; 9(12):1243. doi: 10.3390/antiox9121243. PMID: 33297587; PMCID: PMC7762380.
  3. Lee BJ, Kim B, Lee K. Air pollution exposure and cardiovascular disease. Toxicol Res. 2014 Jun;30(2):71-5. doi: 10.5487/TR.2014.30.2.071. PMID: 25071915; PMCID: PMC4112067.
  4. Cosselman KE, Navas-Acien A, Kaufman JD. Environmental factors in cardiovascular disease. Nat Rev Cardiol. 2015 Nov;12(11):627-42. doi: 10.1038/nrcardio.2015.152. Epub 2015 Oct 13. PMID: 26461967.
  5. Jayawardena TU, Asanka Sanjeewa KK, Shanura Fernando IP, Ryu BM, Kang MC, Jee Y, Lee WW, Jeon YJ. Sargassum horneri (Turner) C. Agardh ethanol extract inhibits the fine dust inflammation response via activating Nrf2/HO-1 signaling in RAW 264.7 cells. BMC Complement Altern Med. 2018 Sep 10;18(1):249. doi: 10.1186/s12906-018-2314-6. PMID: 30200963; PMCID: PMC6131869.
  6. Shukla A, Timblin C, BeruBe K, Gordon T, McKinney W, Driscoll K, Vacek P, Mossman BT. Inhaled particulate matter causes expression of nuclear factor (NF)-kappaB-related genes and oxidant-dependent NF-kappaB activation in vitro. Am J Respir Cell Mol Biol. 2000 Aug;23(2):182-7. doi: 10.1165/ajrcmb.23.2.4035. PMID: 10919984.
  7. Bernard K, Hecker L, Luckhardt TR, Cheng G, Thannickal VJ. NADPH oxidases in lung health and disease. Antioxid Redox Signal. 2014 Jun 10;20(17):2838-53. doi: 10.1089/ars.2013.5608. Epub 2014 Jan 3. PMID: 24093231; PMCID: PMC4026303.
  8. Schepers E, Speer T, Bode-Böger SM, Fliser D, Kielstein JT. Dimethylarginines ADMA and SDMA: the real water-soluble small toxins? Semin Nephrol. 2014 Mar;34(2):97-105. doi: 10.1016/j.semnephrol.2014.02.003. Epub 2014 Feb 17. PMID: 24780466.
  9. Tain YL, Hsu CT. Toxic dimethylarginines: Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). Toxins (Basel) 2017; 9(3):92. doi: 10.3390/toxins9030092.
  10. Cooke JP. Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol. 2000 Sep;20(9):2032-7. doi: 10.1161/01.atv.20.9.2032. PMID: 10978245.
  11. Park MJ, Oh KS, Nho JH, Kim GY, Kim DI. Asymmetric dimethylarginine (ADMA) treatment induces apoptosis in cultured rat mesangial cells via endoplasmic reticulum stress activation. Cell Biol Int. 2016 Jun;40(6):662-70. doi: 10.1002/cbin.10602. Epub 2016 Apr 6. PMID: 26992443.
  12. Pekarova M, Kubala L, Martiskova H, Bino L, Twarogova M, Klinke A, Rudolph TK, Kuchtova Z, Kolarova H, Ambrozova G, Kuchta R, Kadlec J, Lojek A. Asymmetric dimethylarginine regulates the lipopolysaccharide-induced nitric oxide production in macrophages by suppressing the activation of NF-kappaB and iNOS expression. Eur J Pharmacol. 2013 Aug 5;713(1-3):68-77. doi: 10.1016/j.ejphar.2013.05.001. Epub 2013 May 9. PMID: 23665490.
  13. Kim J, Choi H, Choi DH, Park K, Kim HJ, Park M. Application of green tea catechins, polysaccharides, and flavonol prevent fine dust induced bronchial damage by modulating inflammation and airway cilia. Sci Rep. 2021 Jan 26;11(1):2232. doi: 10.1038/s41598-021-81989-9. PMID: 33500561; PMCID: PMC7838266.
  14. Knickle A, Fernando W, Greenshields AL, Rupasinghe HPV, Hoskin DW. Myricetin-induced apoptosis of triple-negative breast cancer cells is mediated by the iron-dependent generation of reactive oxygen species from hydrogen peroxide. Food Chem Toxicol. 2018 Aug;118:154-167. doi: 10.1016/j.fct.2018.05.005. Epub 2018 May 6. PMID: 29742465.
  15. Wang L, Lee W, Cui YR, Ahn G, Jeon YJ. Protective effect of green tea catechin against urban fine dust particle-induced skin aging by regulation of NF-κB, AP-1, and MAPKs signaling pathways. Environ Pollut. 2019 Sep;252(Pt B):1318-1324. doi: 10.1016/j.envpol.2019.06.029. Epub 2019 Jun 14. PMID: 31252129.
  16. Yizhong D, Lu K, Zhongyu D, Shen Y. The complete chloroplast genome sequence of Tussilago farfara(Asteraceae). Mitochondrial DNA B Resour. 2022 Mar 25;7(3):528-530. doi: 10.1080/23802359.2021.2005494. PMID: 35356793; PMCID: PMC8959504.
  17. Chen S, Dong L, Quan H, Zhou X, Ma J, Xia W, Zhou H, Fu X. A review of the ethnobotanical value, phytochemistry, pharmacology, toxicity and quality control of Tussilago farfara (coltsfoot). J Ethnopharmacol. 2021 Mar 1;267:113478. doi: 10.1016/j.jep.2020.113478. Epub 2020 Oct 16. PMID: 33069788; PMCID: PMC7561605.
  18. Röder E, Wiedenfeld H, Jost EJ. Tussilagin - ein neues Pyrrolizidinalkaloid aus Tussilago farfara [Tussilagine - a new pyrrolizidine alkaloid from Tussilago farfara]. Planta Med. 1981 Sep;43(1):99-102. German. doi: 10.1055/s-2007-971485. PMID: 17402021.
  19. Qin K, Liu CH, Qi YX, Li K. Evaluation of antioxidant activity of polysaccharides from Tussilago farfara by flow injection analysis. Asian J Chem. 2014; 26(10):3073–3076. doi:10.14233/ajchem.2014.16685.
  20. Qu H, Yang W, Li J. Structural characterization of a polysaccharide from the flower buds of Tussilago farfara, and its effect on proliferation and apoptosis of A549 human non-small lung cancer cell line. Int J Biol Macromol. 2018 Jul 1;113:849-858. doi: 10.1016/j.ijbiomac.2018.03.005. Epub 2018 Mar 2. PMID: 29505876.
  21. Schramm S, Köhler N, Rozhon W. Pyrrolizidine Alkaloids: Biosynthesis, Biological Activities and Occurrence in Crop Plants. Molecules. 2019 Jan 30;24(3):498. doi: 10.3390/molecules24030498. PMID: 30704105; PMCID: PMC6385001.
  22. Kujur W, Gurram RK, Haleem N, Maurya SK, Agrewala JN. Caerulomycin A inhibits Th2 cell activity: a possible role in the management of asthma. Sci Rep. 2015 Oct 20;5:15396. doi: 10.1038/srep15396. PMID: 26481184; PMCID: PMC4612543.
  23. Guan WJ, Zheng XY, Chung KF, Zhong NS. Impact of air pollution on the burden of chronic respiratory diseases in China: time for urgent action. Lancet. 2016 Oct 15;388(10054):1939-1951. doi: 10.1016/S0140-6736(16)31597-5. PMID: 27751401.
  24. Castañeda AR, Bein KJ, Smiley-Jewell S, Pinkerton KE. Fine particulate matter (PM5) enhances allergic sensitization in BALB/c mice. J Toxicol Environ Health A. 2017;80(4):197-207. doi: 10.1080/15287394.2016.1222920. Epub 2017 May 11. PMID: 28494199; PMCID: PMC6159927.
  25. Safonova EA, Lopatina KA, Razina TG, Zueva EP, Gur'ev AM, Belousov MV. Effects of Tussilago farfara Polysaccharides on the Expression of PD-1 (CD279) and PD-L1 (CD274) in Peripheral Blood and Tumor Tissue Lymphocytes in Mice with Lewis Lung Carcinoma. Bull Exp Biol Med. 2020 Jul;169(3):378-382. doi: 10.1007/s10517-020-04891-w. Epub 2020 Aug 4. PMID: 32749562.
  26. Xu LT, Wang T, Fang KL, Zhao Y, Wang XN, Ren DM, Shen T. The ethanol extract of flower buds of Tussilago farfara attenuates cigarette smoke-induced lung inflammation through regulating NLRP3 inflammasome, Nrf2, and NF-κB. J Ethnopharmacol. 2022 Jan 30;283:114694. doi: 10.1016/j.jep.2021.114694. Epub 2021 Sep 30. PMID: 34601084.
  27. Valavanidis A, Vlachogianni T, Fiotakis K, Loridas S. Pulmonary oxidative stress, inflammation and cancer: respirable particulate matter, fibrous dusts and ozone as major causes of lung carcinogenesis through reactive oxygen species mechanisms. Int J Environ Res Public Health. 2013 Aug 27;10(9):3886-907. doi: 10.3390/ijerph10093886. PMID: 23985773; PMCID: PMC3799517.
  28. Pacheco KA. Epigenetics mediate environment : gene effects on occupational sensitization. Curr Opin Allergy Clin Immunol. 2012 Apr;12(2):111-8. doi: 10.1097/ACI.0b013e328351518f. PMID: 22306555.
  29. Esmaeil N, Gharagozloo M, Rezaei A, Grunig G. Dust events, pulmonary diseases and immune system. Am J Clin Exp Immunol. 2014 Feb 27;3(1):20-9. PMID: 24660118; PMCID: PMC3960758.
  30. Böger RH. Live and let die: asymmetric dimethylarginine and septic shock. Crit Care. 2006;10(6):169. doi: 10.1186/cc5076. PMID: 17094795; PMCID: PMC1794448.
  31. Liu X, Xu X, Shang R, Chen Y. Asymmetric dimethylarginine (ADMA) as an important risk factor for the increased cardiovascular diseases and heart failure in chronic kidney disease. Nitric Oxide. 2018 Aug 1;78:113-120. doi: 10.1016/j.niox.2018.06.004. Epub 2018 Jun 19. PMID: 29928990; PMCID: PMC6301111.
  32. Hermenegildo C, Medina P, Peiró M, Segarra G, Vila JM, Ortega J, Lluch S. Plasma concentration of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, is elevated in hyperthyroid patients. J Clin Endocrinol Metab. 2002 Dec;87(12):5636-40. doi: 10.1210/jc.2002-020905. PMID: 12466365.
  33. Bonser LR, Erle DJ. Airway Mucus and Asthma: The Role of MUC5AC and MUC5B. J Clin Med. 2017 Nov 29;6(12):112. doi: 10.3390/jcm6120112. PMID: 29186064; PMCID: PMC5742801.
  34. Grace MS, Baxter M, Dubuis E, Birrell MA, Belvisi MG. Transient receptor potential (TRP) channels in the airway: role in airway disease. Br J Pharmacol. 2014 May;171(10):2593-607. doi: 10.1111/bph.12538. PMID: 24286227; PMCID: PMC4009002.
  35. Dietrich A, Steinritz D, Gudermann T. Transient receptor potential (TRP) channels as molecular targets in lung toxicology and associated diseases. Cell Calcium. 2017 Nov;67:123-137. doi: 10.1016/j.ceca.2017.04.005. Epub 2017 Apr 26. PMID: 28499580.
  36. Jones MR, Simms BT, Lupa MM, Kogan MS, Mizgerd JP. Lung NF-kappaB activation and neutrophil recruitment require IL-1 and TNF receptor signaling during pneumococcal pneumonia. J Immunol. 2005 Dec 1;175(11):7530-5. doi: 10.4049/jimmunol.175.11.7530. PMID: 16301661; PMCID: PMC2723739.


Similar Articles

Recently Viewed

  • Hypercalcaemic Crisis Associated with Hyperthyroidism: A Rare and Challenging Presentation
    Karthik Baburaj*, Priya Thottiyil Nair, Abeed Hussain and Vimal MV Karthik Baburaj*, Priya Thottiyil Nair, Abeed Hussain, Vimal MV. Hypercalcaemic Crisis Associated with Hyperthyroidism: A Rare and Challenging Presentation. Ann Clin Endocrinol Metabol. 2024: doi: 10.29328/journal.acem.1001029; 8: 001-003
  • Physicians’ Anxiety Post-COVID Pandemic: A Cross-Sectional Study
    Ismail Hanine*, Mouna Chtibi, Kenza Hajjami, Siham Belbachir, Mohamed Kadiri and Abderrazzak Ouanass Ismail Hanine*, Mouna Chtibi, Kenza Hajjami, Siham Belbachir, Mohamed Kadiri, Abderrazzak Ouanass. Physicians’ Anxiety Post-COVID Pandemic: A Cross-Sectional Study. Arch Psychiatr Ment Health. 2024: doi: 10.29328/journal.apmh.1001054; 8: 032-037
  • Current anesthesıa for Cesarean Sectıon
    Demet Dogan Erol* and Ismail Aytac Demet Dogan Erol*, Ismail Aytac. Current anesthesıa for Cesarean Sectıon. Clin J Obstet Gynecol. 2018: doi: 10.29328/journal.cjog.1001011; 1: 061-066
  • Therapy of Walker Carcinosarcoma with Pectin and Cyclophosphane
    NY Alimzhanov, ISh Chakeev, BN Lepshin, IO Kudaibergenova, BA Shaimurzayeva, LV Serikova and Sh Jorobekova* NY Alimzhanov, ISh Chakeev, BN Lepshin, IO Kudaibergenova, BA Shaimurzayeva, LV Serikova, Sh Jorobekova*. Therapy of Walker Carcinosarcoma with Pectin and Cyclophosphane. J Radiol Oncol. 2023: doi: 10.29328/journal.jro.1001056; 7: 066-070
  • Acute Inflammatory Reaction After Radiotherapy to Bilateral Orbital Metastasis from Melanoma
    Christopher J Issa, Batoul Nasser*, Batoul Mazraani, Kevin T Eid, Bailey Loving and Thomas J Quinn and Muayad F Almahariq Christopher J Issa, Batoul Nasser*, Batoul Mazraani, Kevin T Eid, Bailey Loving, Thomas J Quinn and Muayad F Almahariq. Acute Inflammatory Reaction After Radiotherapy to Bilateral Orbital Metastasis from Melanoma. J Radiol Oncol. 2023: doi: 10.29328/journal.jro.1001054; 7: 056-057

Read More

Most Viewed

Read More

Help ?