Skip to main content

Protective effect of water extract of guibi-tang against pulmonary inflammation induced by cigarette smoke and lipopolysaccharide

Abstract

Water extract of guibi-tang (GB), a traditional Chinese, Japanese, and Korean herbal medicine, is used to treat memory impairment, insomnia, and peptic ulcers. The aim of this study was to investigate the protective effects of GB on pulmonary inflammation induced by cigarette smoke (CS) and lipopolysaccharide (LPS). C57BL/6 mice were used to develop a pulmonary inflammation model by exposing them to CS for 1 h per day for 7 days. LPS was intranasally administered to mice under mild anesthesia on day 5. GB was administered 1 h before CS exposure at doses of 50 or 100 mg/kg for 7 days. Our results showed that GB suppressed the CS and LPS induced elevation in inflammatory cell counts in the bronchoalveolar lavage fluid (BALF), with significant reductions in protein, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 levels. Histological studies revealed that GB decreased the inflammatory cell infiltration into lung tissue caused by CS- and LPS-exposure. GB also significantly decreased the CS and LPS-induced expression of inducible nitric oxide synthase (iNOS) in the lung tissue. Taken together, GB effectively attenuated airway inflammation caused by CS and LPS. These results indicate that GB is a potential therapeutic herbal formula for pulmonary inflammatory disease.

References

  1. Scherer PM, Chen DL. Imaging Pulmonary Inflammation. J Nucl Med 2016; 57(11): 1764–1770.

    Article  CAS  Google Scholar 

  2. Abdul Roda M, Sadik M, Gaggar A, Hardison MT, Jablonsky MJ, Braber S, Blalock JE, Redegeld FA, Folkerts G, Jackson PL. Targeting prolyl endopeptidase with valproic acid as a potential modulator of neutrophilic inflammation. PLoS One 2014; 9(5): e97594.

    Article  Google Scholar 

  3. Boskabady MH, Gholami Mhtaj L. Effect of the Zataria multiflora on systemic inflammation of experimental animals model of COPD. Biomed Res Int 2014; 2014: 802189.

    PubMed  PubMed Central  Google Scholar 

  4. Liu H, Ren J, Chen H, Huang Y, Li H, Zhang Z, Wang J. Resveratrol protects against cigarette smoke-induced oxidative damage and pulmonary inflammation. J Biochem Mol Toxicol 2014; 28(10): 465–471.

    Article  Google Scholar 

  5. Liu MH, Lin AH, Lee HF, Ko HK, Lee TS, Kou YR. Paeonol attenuates cigarette smoke-induced lung inflammation by inhibiting ROS-sensitive inflammatory signaling. Mediators Inflamm 2014; 2014: 651890.

    PubMed  PubMed Central  Google Scholar 

  6. Hsiao HM, Sapinoro RE, Thatcher TH, Croasdell A, Levy EP, Fulton RA, Olsen KC, Pollock SJ, Serhan CN, Phipps RP, Sime PJ. A novel anti-inflammatory and pro-resolving role for resolvin D1 in acute cigarette smoke-induced lung inflammation. PLoS One 2013; 8(3): e58258.

    Article  Google Scholar 

  7. Nikota JK, Shen P, Morissette MC, Fernandes K, Roos A, Chu DK, Barra NG, Iwakura Y, Kolbeck R, Humbles AA, Stampfli MR. Cigarette smoke primes the pulmonary environment to IL-1α/CXCR-2-dependent nontypeable Haemophilus influenzae-exacerbated neutrophilia in mice. J Immunol 2014; 193(6): 3134–3145.

    Article  CAS  Google Scholar 

  8. Grommes J, Soehnlein O. Contribution of neutrophils to acute lung injury. Mol Med 2011; 17(3-4): 293–307.

    Article  CAS  Google Scholar 

  9. Berry M, Hargadon B, Morgan A, Shelley M, Richter J, Shaw D, Green RH, Brightling C, Wardlaw AJ, Pavord ID. Alveolar nitric oxide in adults with asthma: evidence of distal lung inflammation in refractory asthma. Eur Respir J 2005; 25(6): 986–991.

    Article  CAS  Google Scholar 

  10. Bhattacharjee A, Prasad SK, Pal S, Maji B, Banerjee A, Das D, Bose A, Chatterjee N, Mukherjee S. Possible involvement of iNOS and TNF-α in nutritional intervention against nicotine-induced pancreatic islet cell damage. Biomed Pharmacother 2016; 84: 1727–1738.

    Article  CAS  Google Scholar 

  11. Lee H, Park JR, Kim EJ, Kim WJ, Hong SH, Park SM, Yang SR. Cigarette smoke-mediated oxidative stress induces apoptosis via the MAPKs/STAT1 pathway in mouse lung fibroblasts. Toxicol Lett 2016; 240(1): 140–148.

    Article  CAS  Google Scholar 

  12. Gupta I, Ganguly S, Rozanas CR, Stuehr DJ, Panda K. Ascorbate attenuates pulmonary emphysema by inhibiting tobacco smoke and Rtp801-triggered lung protein modification and proteolysis. Proc Natl Acad Sci USA 2016; 113(29): E4208–4217.

    Article  Google Scholar 

  13. Lee YM, Lee YR, Kim CS, Jo K, Sohn E, Kim JS, Kim J. Effect of Guibi-Tang, a Traditional Herbal Formula, on Retinal Neovascularization in a Mouse Model of Proliferative Retinopathy. Int J Mol Sci 2015; 16(12): 29900–29910.

    Article  CAS  Google Scholar 

  14. Lee MY, Seo CS, Kim J Y, Shin HK. Genotoxicity evaluation of Guibi-Tang extract using an in vitro bacterial reverse mutation assay, chromosome aberration assay, and in vivo micronucleus test. BMC Complement Altern Med 2014; 14: 215.

    Article  Google Scholar 

  15. Oh MS, Huh Y, Bae H, Ahn DK, Park SK. The multi-herbal formula Guibi-tang enhances memory and increases cell proliferation in the rat hippocampus. Neurosci Lett 2005; 379(3): 205–208.

    Article  CAS  Google Scholar 

  16. Yim NH, Kim A, Liang C, Cho WK, Ma JY. Guibitang, a traditional herbal medicine, induces apoptotic death in A431 cells by regulating the activities of mitogen-activated protein kinases. BMC Complement Altern Med 2014; 14: 344.

    Article  Google Scholar 

  17. Abbott-Banner KH, Page CP. Dual PDE3/4 and PDE4 inhibitors: novel treatments for COPD and other inflammatory airway diseases. Basic Clin Pharmacol Toxicol 2014; 114(5): 365–376.

    Article  CAS  Google Scholar 

  18. Kubo S, Kobayashi M, Iwata M, Miyata K, Takahashi K, Shimizu Y. Anti-neutrophilic inflammatory activity of ASP3258, a novel phosphodiesterase type 4 inhibitor. Int Immunopharmacol 2012; 12(1): 59–63.

    Article  CAS  Google Scholar 

  19. Yoshida T, Tuder RM. Pathobiology of cigarette smoke-induced chronic obstructive pulmonary disease. Physiol Rev 2007; 87(3): 1047–1082.

    Article  CAS  Google Scholar 

  20. John-Schuster G, Günter S, Hager K, Conlon TM, Eickelberg O, Yildirim AÖ. Inflammaging increases susceptibility to cigarette smoke-induced COPD. Oncotarget 2016; 7(21): 30068–30083.

    Article  Google Scholar 

  21. Leberl M, Kratzer A, Taraseviciene-Stewart L. Tobacco smoke induced COPD/emphysema in the animal model-are we all on the same page? Front Physiol 2013; 4: 91.

    Article  CAS  Google Scholar 

  22. Li Y, Yu G, Yuan S, Tan C, Lian P, Fu L, Hou Q, Xu B, Wang H. Cigarette Smoke-Induced Pulmonary Inflammation and Autophagy Are Attenuated in Ephx2-Deficient Mice. Inflammation 2017; 40(2): 497–510.

    Article  CAS  Google Scholar 

  23. D’hulst AI, Vermaelen KY, Brusselle GG, Joos GF, Pauwels RA. Time course of cigarette smoke-induced pulmonary inflammation in mice. Eur Respir J 2005; 26(2): 204–213.

    Article  Google Scholar 

  24. O’Donnell R, Breen D, Wilson S, Djukanovic R. Inflammatory cells in the airways in COPD. Thorax 2006; 61(5): 448–454.

    Article  Google Scholar 

  25. Rovina N, Koutsoukou A, Koulouris NG. Inflammation and immune response in COPD: where do we stand? Mediators Inflamm 2013; 2013:413735.

    Article  Google Scholar 

  26. Karimi K, Sarir H, Mortaz E, Smit JJ, Hosseini H, De Kimpe SJ, Nijkamp F P, Folkerts G. Toll-like receptor-4 mediates cigarette smoke-induced cytokine production by human macrophages. Respir Res 2006; 7: 66.

    Article  Google Scholar 

  27. Teasdale JE, Hazell GG, Peachey AM, Sala-Newby GB, Hindmarch CC, McKay TR, Bond M, Newby AC, White SJ. Cigarette smoke extract profoundly suppresses TNFα-mediated proinflammatory gene expression through upregulation of ATF3 in human coronary artery endothelial cells. Sci Rep 2017; 7: 39945.

    Article  CAS  Google Scholar 

  28. Hubeau C, Kubera JE, Masek-Hammerman K, Williams CM. Interleukin-6 neutralization alleviates pulmonary inflammation in mice exposed to cigarette smoke and poly(I:C). Clin Sci (Lond) 2013; 125(10): 483–493.

    Article  CAS  Google Scholar 

  29. Wei J, Xiong XF, Lin YH, Zheng BX, Cheng D Y. Association between serum interleukin-6 concentrations and chronic obstructive pulmonary disease: a systematic review and meta-analysis. PeerJ 2015; 3: e1199.

    Article  Google Scholar 

  30. He JQ, Foreman MG, Shumansky K, Zhang X, Akhabir L, Sin DD, Man SF, DeMeo DL, Litonjua AA, Silverman EK, Connett JE, Anthonisen NR, Wise RA, Paré PD, Sandford AJ. Associations of IL6 polymorphisms with lung function decline and COPD. Thorax 2009; 64(8): 698–704.

    Article  Google Scholar 

  31. Malerba M, Radaeli A, Olivini A, Damiani G, Ragnoli B, Montuschi P, Ricciardolo FL. Exhaled nitric oxide as a biomarker in COPD and related comorbidities. Biomed Res Int 2014; 2014: 271918.

    Article  Google Scholar 

  32. Hesslinger C, Strub A, Boer R, Ulrich WR, Lehner MD, Braun C. Inhibition of inducible nitric oxide synthase in respiratory diseases. Biochem Soc Trans 2009; 37(Pt 4): 886–891.

    Article  CAS  Google Scholar 

  33. Agustí A, Morlá M, Sauleda J, Saus C, Busquets X. NF-kappaB activation and iNOS upregulation in skeletal muscle of patients with COPD and low body weight. Thorax 2004; 59(6): 483–487.

    Article  Google Scholar 

  34. Wright JL, Zhou S, Churg A. Pulmonary hypertension and vascular oxidative damage in cigarette smoke exposed eNOS(-/-) mice and human smokers. Inhal Toxicol 2012; 24(11): 732–740.

    Article  CAS  Google Scholar 

  35. Li XQ, Cai LM, Liu J, Ma YL, Kong YH, Li H, Jiang M. Liquiritin suppresses UVB-induced skin injury through prevention of inflammation, oxidative stress and apoptosis through the TLR4/ MyD88/NF-κB and MAPK/caspase signaling pathways. Int J Mol Med 2018; 42(3):1445–1459.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Guan Y, Li FF, Hong L, Yan XF, Tan GL, He JS, Dong XW, Bao MJ, Xie QM. Protective effects of liquiritin apioside on cigarette smoke-induced lung epithelial cell injury. Fundam Clin Pharmacol 2012; 26(4): 473–483.

    Article  CAS  Google Scholar 

  37. Xiong Y, Wang J, Yu H, Zhang X, Miao C, Ma S. The effects of nodakenin on airway inflammation, hyper-responsiveness and remodeling in a murine model of allergic asthma. Immunopharmacol Immunotoxicol 2014; 36(5): 341–348.

    Article  CAS  Google Scholar 

  38. Ram A, Mabalirajan U, Das M, Bhattacharya I, Dinda AK, Gangal SV, Ghosh B. Glycyrrhizin alleviates experimental allergic asthma in mice. Int Immunopharmacol 2006; 6(9): 1468–1477

    Article  CAS  Google Scholar 

  39. Cai X, Wang X, Li J, Chen S. Protective effect of glycyrrhizin on myocardial ischemia/reperfusion injury-induced oxidative stress, inducible nitric oxide synthase and inflammatory reactions through high-mobility group box 1 and mitogen-activated protein kinase expression. Exp Ther Med 2017; 14(2): 1219–1226.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to In-Sik Shin.

Rights and permissions

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://doi.org/creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shin, NR., Jung, TY., Seo, CS. et al. Protective effect of water extract of guibi-tang against pulmonary inflammation induced by cigarette smoke and lipopolysaccharide. Lab Anim Res 34, 92–100 (2018). https://doi.org/10.5625/lar.2018.34.3.92

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.5625/lar.2018.34.3.92

Keywords