Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
권호 표지
DOI QR코드

DOI QR Code

Saponin attenuates diesel exhaust particle (DEP)-induced MUC5AC expression and pro-inflammatory cytokine upregulation via TLR4/TRIF/NF-𝛋B signaling pathway in airway epithelium and ovalbumin (OVA)-sensitized mice

  • Jo, Sooyeon (Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University) ;
  • Na, Hyung Gyun (Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University) ;
  • Choi, Yoon Seok (Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University) ;
  • Bae, Chang Hoon (Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University) ;
  • Song, Si-Youn (Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University) ;
  • Kim, Yong-Dae (Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University)
  • Received : 2021.11.17
  • Accepted : 2022.03.31
  • Published : 2022.11.01
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Diesel exhaust particle (DEP) is a harmful kind of particulate matter known to exacerbate pre-existing respiratory diseases. Although their adverse effects on airway pathologies have been widely studied, the mechanistic analysis of signaling pathways and potential targets in reducing DEP-induced mucin secretion and pro-inflammatory cytokine production remain elusive. We, for the first time, investigated the effects of Korean Red Ginseng (KRG) extracts on mucin overproduction and airway inflammation induced by DEP. Methods: The effects of KRG and saponin on DEP-induced expression of MUC5AC and interleukin (IL)-6/8 were examined by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) in human airway epithelial NCI-H292 cells. We conducted Western blotting analysis to analyze the associated signaling pathways. To evaluate the effects of saponin treatment on DEP-induced MUC5AC expression and inflammatory cell infiltrations in ovalbumin (OVA)-sensitized mice, immunohistochemical (IHC) staining and real-time PCR were implemented. Results: The KRG extracts markedly attenuated DEP-induced MUC5AC expression in vitro by inhibiting the TLR4/TRIF/NF-𝛋B pathway. Furthermore, KRG and saponin inhibited DEP-induced pro-inflammatory cytokine IL-6/8 production. The in vivo study revealed that saponin blocked DEP-induced inflammation, mucin production and MUC5AC expression. Conclusion: Our study revealed that KRG extracts have inhibitory effects on DEP-induced expression of MUC5AC and the production of pro-inflammatory cytokines. This finding provides novel insights into the mechanism by which saponin alleviates diesel-susceptible airway inflammation, elucidating its potential as a phytotherapeutic agent for inflammatory pathologies of airway.

Keywords

Acknowledgement

This research was supported by the 2017 Korean Society of Ginseng.

References

  1. Ristovski ZD, Miljevic B, Surawski NC, Morawska L, Fong KM, Goh F, et al. Respiratory health effects of diesel particulate matter. Respirology 2012;17(2):201-12. https://doi.org/10.1111/j.1440-1843.2011.02109.x
  2. Ris CUS. EPA health assessment for diesel engine exhaust: a review. Inhal Toxicol 2007;19(Suppl 1):229-39. https://doi.org/10.1080/08958370701497960
  3. Brandt EB, Kovacic MB, Lee GB, Gibson AM, Acciani TH, Le Cras TD, et al. Diesel exhaust particle induction of IL-17A contributes to severe asthma. J Allergy Clin Immunol 2013;132(5). 1194-204.e2. https://doi.org/10.1016/j.jaci.2013.06.048
  4. de Homdedeu M, Cruz M, Sanchez-Diez S, O I, Romero-Mesones C, V J, et al. The immunomodulatory effects of diesel exhaust particles in asthma. Environ Pollut 2020;263(Pt A):114600. https://doi.org/10.1016/j.envpol.2020.114600
  5. Kim BG, Lee PH, Lee SH, Kim YE, Shin MY, Kang Y, et al. Long-term effects of diesel exhaust particles on airway inflammation and remodeling in a mouse model. Allergy Asthma Immunol Res 2016;8(3):246-56. https://doi.org/10.4168/aair.2016.8.3.246
  6. Stevens T, Cho SH, Linak WP, Gilmour MI. Differential potentiation of allergic lung disease in mice exposed to chemically distinct diesel samples. Toxicol Sci 2009;107(2):522-34. https://doi.org/10.1093/toxsci/kfn248
  7. Bonvallot V, Baeza-Squiban A, Baulig A, Brulant S, Boland S, Muzeau F, et al. Organic compounds from diesel exhaust particles elicit a proinflammatory response in human airway epithelial cells and induce cytochrome p450 1A1 expression. Am J Respir Cell Mol Biol 2001;25(4):515-21. https://doi.org/10.1165/ajrcmb.25.4.4515
  8. Brinchmann BC, Skuland T, Rambol MH, Szoke K, Brinchmann JE, Gutleb AC, et al. Lipophilic components of diesel exhaust particles induce proinflammatory responses in human endothelial cells through AhR dependent pathway(s). Part Fibre Toxicol 2018;15(1):21. https://doi.org/10.1186/s12989-018-0257-1
  9. Totlandsdal AI, Herseth JI, Bolling AK, Kubatova A, Braun A, Cochran RE, et al. Differential effects of the particle core and organic extract of diesel exhaust particles. Toxicol Lett 2012;208(3):262-8. https://doi.org/10.1016/j.toxlet.2011.10.025
  10. Ciuman RR. Phytotherapeutic and naturopathic adjuvant therapies in otorhinolaryngology. Eur Arch Oto-Rhino-Laryngol 2012;269(2):389-97. https://doi.org/10.1007/s00405-011-1755-z
  11. Hyun SH, Kim SW, Seo HW, Youn SH, Kyung JS, Lee YY, et al. Physiological and pharmacological features of the non-saponin components in Korean Red Ginseng. J Ginseng Res 2020;44(4):527-37. https://doi.org/10.1016/j.jgr.2020.01.005
  12. Song H, Kim S, Ji K, Kim B, Yang W, Han C, et al. Respiratory protective effect of Salvia plebeia R. Br. extracts against ambient particulate matter-induced airway inflammation. Kor J Med Crop Sci 2017;25:269-81. https://doi.org/10.7783/KJMCS.2017.25.5.269
  13. Shin H, Gwak H, Lee M, Kyung J, Jang K, Han C, et al. Enhancement of respiratory protective and therapeutic effect of Salvia plebeia R. Br. extracts in combination with Korean red ginseng. Kor J Med Crop Sci 2019;27:218-31. https://doi.org/10.7783/KJMCS.2019.27.3.218
  14. Lee PH, Kim BG, Park MK, Hong J, Lee YG, Jang AS. The impact of diesel exhaust particles on tight junctional proteins on nose and lung in a mouse model. Allergy Asthma Immunol Res 2021;13(2):350-2.
  15. Kim N, Han DH, Suh MW, Lee JH, Oh SH, Park MK. Effect of lipopolysaccharide on diesel exhaust particle-induced junctional dysfunction in primary human nasal epithelial cells. Environ Pollut 2019;248:736-42. https://doi.org/10.1016/j.envpol.2019.02.082
  16. Na HG, Kim YD, Choi YS, Bae CH, Song SY. Diesel exhaust particles elevate MUC5AC and MUC5B expression via the TLR4-mediated activation of ERK1/2, p38 MAPK, and NF-kB signaling pathways in human airway epithelial cells. Biochem Biophys Res Commun 2019;512(1):53-9. https://doi.org/10.1016/j.bbrc.2019.02.146
  17. Shin SH, Ye MK, Lee DW, Kang BJ, Chae MH. Effect of Korean red ginseng and Rg3 on asian sand dust-induced MUC5AC, MUC5B, and MUC8 expression in bronchial epithelial cells. Molecules 2021;26(7):2002. https://doi.org/10.3390/molecules26072002
  18. Kim JH, Lee TJ, Jee-Aee Im, Lee DC. Effect of Korean red ginseng on artificial sand dust(ASD) induced allergic lung inflammation. Biomed Sci Lett 2014;20(3):173-9. https://doi.org/10.15616/BSL.2014.20.3.173
  19. Iqbal H, Rhee D-k. Ginseng alleviates microbial infections of the respiratory tract: a review. J Ginseng Res 2020;44(2):194-204. https://doi.org/10.1016/j.jgr.2019.12.001
  20. Ohtoshi T, Takizawa H, Okazaki H, Kawasaki S, Takeuchi N, Ohta K, et al. Diesel exhaust particles stimulate human airway epithelial cells to produce cytokines relevant to airway inflammation in vitro. J Allergy Clin Immunol 1998;101(6 Pt 1):778-85. https://doi.org/10.1016/S0091-6749(98)70307-0
  21. Reynolds PR, Wasley KM, Allison CH. Diesel particulate matter induces receptor for advanced glycation end-products (RAGE) expression in pulmonary epithelial cells, and RAGE signaling influences NF-kB-mediated inflammation. Environ Health Perspect 2011;119(3):332-6. https://doi.org/10.1289/ehp.1002520
  22. Jung JH, Kang IG, Kim DY, Hwang YJ, Kim ST. The effect of Korean red ginseng on allergic inflammation in a murine model of allergic rhinitis. J Ginseng Res 2013;37(2):167-75. https://doi.org/10.5142/jgr.2013.37.167
  23. Sung JE, Lee HA, Kim JE, Yun WB, An BS, Yang SY, et al. Saponin-enriched extract of Asparagus cochinchinensis alleviates airway inflammation and remodeling in ovalbumin-induced asthma model. Int J Mol Med 2017;40(5): 1365-76. https://doi.org/10.3892/ijmm.2017.3147
  24. Lim H-B, Kim S-H. The effect of crude saponins of Korean red ginseng against airway inflammation and airway hyperresponsiveness induced by diesel exhaust particles in mice. Kor J Med Crop Sci 2009;17(2):90-6.
  25. Song YS, Kim J-H, Na H, Choi YS, Song S-Y, Kim Y-D, et al. Inhibitory effects of protopanaxadiol on lipopolysaccharide-induced reactive oxygen species production and MUC5AC expression in human airway epithelial cells. Kor J Otorhinolaryngol Head Neck Surg 2019;62(9):507-14. https://doi.org/10.3342/kjorl-hns.2018.00920
  26. Choi TY, Kim J-H, Jo S, Lee S, Na H-G, Choi YS, et al. Ginsenoside Rb1 attenuates TGF-b1-induced MUC4/5AC expression and epithelial-mesenchymal transition in human airway epithelial cells. Kor J Otorhinolaryngol Head Neck Surg 2021;64(4):232-9. https://doi.org/10.3342/kjorl-hns.2020.00150