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Oral administration of Ulmus davidiana extract suppresses interleukin-1β expression in LPS-induced immune responses and lung injury

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Abstract

Background

Ulmus davidiana (UD) is a traditional Korean herb medicine that is used to treat inflammatory disorders. UD has been shown to modulate a number of inflammatory processes in vitro or in vivo studies. However, the molecular mechanisms of UD on lipopolysaccharide (LPS)-induced acute lung injury remain to be understood.

Objective

The primary objective of this study is to determine the effect of UD bark water extract on LPS-induced immune responses and lung injury using both in vitro and in vivo models.

Methods

RAW 264.7 cells and a rat model of acute lung injury (ALI) were used to study the effects of UD on several parameters. Nitrite level, lactate dehydrogenase (LDH) level, and superoxide dismutase (SOD) activities were measured. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and plasma transaminase activities in blood were also determined. Pathological investigations were also performed.

Results

LPS infusion resulted in elevated IL-1β mRNA expression, nitrite levels, TNF-α expression, and IL-1β expression in RAW 264.7 cells. LPS infusion also increased levels of nitrite/nitrate, total protein, LDH, and TNF-α in bronchoalveolar lavage fluid, but reduced SOD levels in ex vivo and in vivo models. UD administration ameliorated all these inflammatory markers. In particular, treatment with UD reduced LPS-induced nitrite production in RAW 264.7 cells in a dose-dependent manner. UD treatment also counteracted the LPS-induced increase in alanine aminotransferase (ALT) and aspartate transaminase (AST) activity in rat plasma, leading to a significant reduction in ALT and AST activity.

Conclusions

The results revealed that UD treatment reduces LPS-induced nitrite production, IL-1β mRNA expression, and TNF-α expression. In addition, LPS-induced decrease in SOD level is significantly elevated by UD administration. These results indicate that UD extract merits consideration as a potential drug for treating and/or preventing ALI.

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References

  • Baldus S, Castro L, Eiserich JP, Freeman BA (2001) Is center dot NO news bad news in acute respiratory distress syndrome? Am J Respir Crit Care Med 163:308–310

    CAS  PubMed  Google Scholar 

  • Barnes PJ, Adcock I, Spedding M, Vanhoutte PM (1993) Anti-inflammatory actions of steroids: molecular mechanisms. Trends Pharmacol Sci 14(12):436–441

    CAS  PubMed  Google Scholar 

  • Camussi G, Ronco C, Montrucchio G, Piccoli G (1998) Role of soluble mediators in sepsis and renal failure. Kidney Int Suppl 53:S38–S42

    Google Scholar 

  • Carreras MC, Pargament GA, Catz SD, Poderoso JJ, Boveris A (1994) Kinetics of nitric oxide and hydrogen peroxide production and formation of peroxynitrite during the respiratory burst of human neutrophils. FEBS Lett 341:65–68

    CAS  PubMed  Google Scholar 

  • Chen H, Bai C, Wang X (2010) The value of the lipopolysaccharide-induced acute lung injury model in respiratory medicine. Expert Rev Respir Med 4:773–783

    CAS  PubMed  Google Scholar 

  • Cheng L, Ren Y, Lin D, Peng S, Zhong B, Ma Z (2017) The anti-inflammatory properties of citrus wilsonii tanaka extract in LPS-induced RAW 264.7 and primary mouse bone marrow-derived dendritic cells. Molecules 22:1213–1226

    PubMed Central  Google Scholar 

  • Choi Y, Lee MK, Lim SY, Sung SH, Kim YC (2009) Inhibition of inducible NO synthase, cyclooxygenase-2 and interleukin-1beta by torilin is mediated by mitogen-activated protein kinases in microglial BV2 cells. Br J Pharmacol 156(6):933–940

    CAS  PubMed  PubMed Central  Google Scholar 

  • Choi SY, Lee S, Choi WH, Lee Y, Jo YO, Ha TY (2010) Isolation and anti-inflammatory activity of Bakuchiol from Ulmus davidiana var. japonica. J Med Food 13(4):1019–1023

    CAS  PubMed  Google Scholar 

  • Drent M, Cobben NA, Henderson RF, Wouters EF, van Dieijen-Visser M (1996) Usefulness of lactate dehydrogenase and its isoenzymes as indicators of lung damage or inflammation. Eur Respir J 9:1736–1742

    CAS  PubMed  Google Scholar 

  • El-Agamy DS (2011) Nilotinib ameliorates lipopolysaccharide-induced acute lung injury in rats. Toxicol Appl Pharmacol 253:153–160

    CAS  PubMed  Google Scholar 

  • Ermert M, Ruppert C, Günther A, Duncker HR, Seeger W, Ermert L (2002) Cell-specific nitric oxide synthase-isoenzyme expression and regulation in response to endotoxin in intact rat lungs. Lab Invest 82:425–441

    CAS  PubMed  Google Scholar 

  • Farley KS, Wang LF, Razavi HM, Law C, Rohan M, McCormack DG, Mehta S (2006) Effects of macrophage inducible nitric oxide synthase in murine septic lung injury. Am J Physiol Lung Cell Mol Physiol 290:L1164–L1172

    CAS  PubMed  Google Scholar 

  • Feihl F, Waeber B, Liaude L (2001) Is nitric oxide overproduction the target of choice for the management of septic shock? Pharmacol Ther 91:179–213

    CAS  PubMed  Google Scholar 

  • Ferguson ND, Frutos-Vivar F, Esteban A, Gordo F, Honrubia T, Peñuelas O, Algora A, García G, Bustos A, Rodríguez I (2007) Clinical risk conditions for acute lung injury in the intensive care unit and hospital ward: a prospective observational study. Crit Care 11:R96

    PubMed  PubMed Central  Google Scholar 

  • Förstermann U, Sessa WC (2012) Nitric oxide synthases: regulation and function. Eur Heart J 33:829–837

    PubMed  Google Scholar 

  • Fulkerson WJ, MacIntyre N, Stamler J, Crapo JD (1996) Pathogenesis and treatment of the adult respiratory distress syndrome. Arch Intern Med 156:29–38

    CAS  PubMed  Google Scholar 

  • Ge ZJ, Jiang G, Zhao YP, Wang GX, Tan YF (2010) Systemic perfluorohexane attenuates lung injury induced by lipopolysaccharide in rats: the role of heme oxygenase-1. Pharmacol Rep 62:170–177

    CAS  PubMed  Google Scholar 

  • Giebelen IA, van Westerloo DJ, LaRosa GJ, de Vos AF, van der Poll T (2007) Local stimulation of alpha7 cholinergic receptors inhibits LPS-induced TNF-alpha release in the mouse lung. Shock 28:700–703

    CAS  PubMed  Google Scholar 

  • Hernaez R, Solà E, Moreau R, Ginès P (2017) Acute-on-chronic liver failure: an update. Gut 66:541–553

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hickey MJ, Sihota E, Amrani A, Santamaria P, Zbytnuik LD, Ng ES, Ho W, Sharkey KA, Kubes P (2002) Inducible nitric oxide synthase (iNOS) in endotoxemia: chimeric mice reveal different cellular sources in various tissues. FASEB J 16:1141–1143

    CAS  PubMed  Google Scholar 

  • Jun CD, Pae HO, Kim YC, Jeong SJ, Yoo JC, Lee EJ, Choi BM, Chae SW, Park RK, Chung HT (1998) Inhibition of nitric oxide synthesis by butanol fraction of the methanol extract of Ulmus davidiana in murine macrophages. J Ethnopharmacol 62(2):129–135

    CAS  PubMed  Google Scholar 

  • Kamata K, Inazu M, Takeda H, Goto H, Matsumiya T, Usui M (2003) Effect of a selective inducible nitric oxide synthase inhibitor on intraocular nitric oxide production in endotoxin-induced uveitis rabbits: in vivo intraocular microdialysis study. Pharmacol Res 47:485–491

    CAS  PubMed  Google Scholar 

  • Kang J, Park KH, Kim JJ, Jo EK, Han MK, Kim UH (2012) The role of CD38 in Fcγ receptor (FcγR)-mediated phagocytosis in murine macrophages. J Biol Chem 287:14502–14514

    CAS  PubMed  PubMed Central  Google Scholar 

  • Keane MP, Donnelly SC, Belperio JA, Goodman RB, Dy M, Burdick MD, Fishbein MC, Strieter RM (2002) Imbalance in the expression of CXC chemokines correlates with bronchoalveolar lavage fluid angiogenic activity and procollagen levels in acute respiratory distress syndrome. J Immunol 169:6515–6521

    CAS  PubMed  Google Scholar 

  • Kim KS, Lee SD, Kim KH, Kil SY, Chung KH, Kim CH (2005) Suppressive effects of a water extract of Ulmus davidiana Planch (Ulmaceae) on collagen-induced arthritis in mice. J Ethnopharmacol 97(1):65–71

    PubMed  Google Scholar 

  • Kim YC, Lee MK, Sung SH, Kim SH (2007) Sesquiterpenes from Ulmus davidiana var. japonica with the inhibitory effects on lipopolysaccharide-induced nitric oxide production. Fitoterapia 78(3):196–199

    CAS  PubMed  Google Scholar 

  • Kim SJ, Kim KH, Kim SJ, Kang HS, Kim JS, Kim MH, Jo JK, Choi JB, Yang YS, Kim GB (2012) Effectiveness of antioxidant and membrane oxygenator in acute respiratory distress syndrome by endotoxin. Kor J Chem Eng 29:1597–1603

    CAS  Google Scholar 

  • Knepler JL Jr, Taher LN, Gupta MP, Patterson C, Pavalko F, Ober MD, Hart CM (2001) Peroxynitrite causes endothelial cell monolayer barrier dysfunction. Am J Physio Cell Physiol 281:C1064–C1075

    CAS  Google Scholar 

  • Kristof AS, Goldberg P, Laubach V, Hussain SN (1998) Role of inducible nitric oxide synthase in endotoxin-induced acute lung injury. Am J Respir Crit Care Med 158:1883–1889

    CAS  PubMed  Google Scholar 

  • Lee SJ, Lim KT (2008) A 116-kDa phytoglycoprotein inhibits aberrant crypt foci formation through modulation of manganese superoxide dismutase, inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-kappa B, activator protein-1, and proliferating cell nuclear antigen in 1,2-dimethylhydrazine/dextran sodium sulfate-treated ICR mice. Eur J Cancer Prev 17(6):479–488

    CAS  PubMed  Google Scholar 

  • Lee Y, Park H, Ryu HS, Chun M, Kang S, Kim HS (2007) Effects of elm bark (Ulmus davidiana var. japonica) extracts on the modulation of immunocompetence in mice. J Med Food 10(1):118–125

    CAS  PubMed  Google Scholar 

  • Lee EH, Park CW, Jung YJ (2013) Root bark of Ulmus davidiana var. japonica restrains acute alcohol-induced hepatic steatosis onset in mice by inhibiting ROS accumulation. Anti-inflammatory and immune-modulating effect of Ulmus davidiana var. japonica Nakai extract on a macrophage cell line and immune cells in the mouse small intestine. J Ethnopharmacol 146(2):608–613

    PubMed  Google Scholar 

  • Lo HP, Ackland-Berglund CE, Pritchard KA Jr, Guice KS, Oldham KT (2001) Attenuated expression of inducible nitric oxide synthase in lung microvascular endothelial cells is associated with an increase in ICAM-1 expression. J Pediatr Surg 36:1136–1142

    CAS  PubMed  Google Scholar 

  • Lucas R, Verin AD, Black SM, Catravas JD (2009) Regulators of endothelial and epithelial barrier integrity and function in acute lung injury. Biochem Pharmacol 77:1763–1772

    CAS  PubMed  PubMed Central  Google Scholar 

  • Matute-Bello G, Frevert CW, Martin TR (2008) Animal models of acute lung injury. Am J Physiol Lung Cell Mol Physiol 295:L379–L399

    CAS  PubMed  PubMed Central  Google Scholar 

  • Meduri GU, Yates CR (2004) Systemic inflammation-associated glucocorticoid resistance and outcome of ARDS, glucocorticoid action: basic and clinical implications Ann N Y Acad Sci 1024:24–53

    CAS  Google Scholar 

  • Mikawa K, Nishina K, Takao Y, Obara H (2003) ONO-1714, a nitric oxide synthase inhibitor, attenuates endotoxin-induced acute lung injury in rabbits. Anesth Analg 97:1751–1755

    CAS  PubMed  Google Scholar 

  • Mirzapoiazova T, Kolosova IA, Moreno L, Sammani S, Garcia JG, Verin AD (2007) Suppression of endotoxin-induced inflammation by taxol. Eur Respir J 30:429–435

    CAS  PubMed  Google Scholar 

  • Numata M, Suzuki S, Miyazawa N, Miyashita A, Nagashima Y, Inoue S, Kaneko T, Okubo T (1998) Inhibition of inducible nitric oxide synthase prevents LPS-induced acute lung injury in dogs. J Immunol 160:3031–3037

    CAS  PubMed  Google Scholar 

  • Nyblom H, Berggren U, Balldin J, Olsson R (2004) High AST/ALT ratio may indicate advanced alcoholic liver disease rather than heavy drinking. Alcohol Alcohol 39:336–339

    CAS  PubMed  Google Scholar 

  • Pan JH, Lim Y, Kim JH, Heo W, Lee KY, Shin HJ, Kim JK, Lee JH, Kim YJ (2017) PLoS One 12(11):e0188381

    PubMed  PubMed Central  Google Scholar 

  • Puneet P, Moochhala S, Bhatia M (2005) Chemokines in acute respiratory distress syndrome. Am J Physiology-Lung Cell Mol Physiol 288(1):L3-L15

    CAS  Google Scholar 

  • Shen W, Gan J, Xu S, Jiang G, Wu H (2009) Penehyclidine hydrochloride attenuates LPS-induced acute lung injury involvement of NF-kappa B pathway. Pharmacol Res 60:296–302

    CAS  PubMed  Google Scholar 

  • Song IK, Kim KS, Suh SJ, Kim MS, Kwon DY, Kim SL, Kim CH (2007) Anti-inflammatory effect of Ulmus davidiana Planch (Ulmaceae) on collagen-induced inflammation in rats. Environ Toxicol Pharmacol 23(1):102–110

    CAS  PubMed  Google Scholar 

  • Steinberg KP, Hudson LD, Goodman RB, Hough CL, Lanken PN, Hyzy R, Thompson BT, Ancukiewicz M (2006) Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 354:1671–1684

    CAS  PubMed  Google Scholar 

  • Suresh V, Mih JD, George SC (2007) Measurement of IL-13-induced iNOS-derived gas phase nitric oxide in human bronchial epithelial cells. Am J Respir Cell Mol Biol 37:97–104

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tan RJ, Lee JS, Manni ML, Fattman CL, Tobolewski JM, Zheng M, Kolls JK, Martin TR, Oury TD (2006) Inflammatory cells as a source of airspace extracellular superoxide dismutase after pulmonary injury. Am J Respir Cell Mol Biol 34:226–232

    CAS  PubMed  Google Scholar 

  • Ware LB (2006) Pathophysiology of acute lung injury and the acute respiratory distress syndrome. Semin Respir Crit Care Med 27:337–349

    PubMed  Google Scholar 

  • Xu XL, Xie QM, Shen YH, Jiang JJ, Chen YY, Yao HY, Zhou JY (2008) Mannose prevents lipopolysaccharide-induced acute lung injury in rats. Inflamm Res 57:104–110

    CAS  PubMed  Google Scholar 

  • Zinetti M, Fantuzzi G, Delgado R, Di Santo E, Ghezzi P, Fratelli M (1995) Endogenous nitric-oxide production by human monocytic cells regulates LPS-induced TNF production. Eur Cytokine Netw 6:45–48

    CAS  PubMed  Google Scholar 

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Acknowledgements

The present study was supported by a Grant (NRF–2013R1A1A2011718 to J-S-K) of the National Research Foundation (NRF) of Korea funded by the Korean government. It was also partially supported by Nambu University Research Support Fund (2018 to K-H-P). The authors thank Prof. Mie-Jae Im for critical reading of the manuscript.

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Author notes

  1. Kwang-Hyun Park and Eun-Yong Chung contributed equally.

Authors and Affiliations

  1. Department of Oriental Pharmaceutical Development, Nambu University, Gwangju, 62271, Republic of Korea

    Kwang-Hyun Park

  2. Department of Emergency Medical Rescue, Nambu University, Gwangju, 62271, Republic of Korea

    Kwang-Hyun Park

  3. Department of Anesthesiology and Pain Medicine, Bucheon St. Mary’s Hospital, Catholic University of Korea, Bucheon, 14647, Republic of Korea

    Eun-Yong Chung & Yu-Na Choi

  4. Department of Biochemistry, Chonbuk National University Medical School, Jeonju, 54907, Republic of Korea

    Hye-Yeon Jang & Jong-Suk Kim

  5. Eouidang Agricultural Company, Wanju, 55360, Republic of Korea

    Gi-Beum Kim

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  1. Kwang-Hyun Park
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Contributions

G-BK and J-SK conceived and designed the study; E-YC, K-HP, and H-YJ collected the data, contributed reagents/materials/analysis tools; and K-HP and G-BK wrote the paper.

Corresponding authors

Correspondence to Jong-Suk Kim or Gi-Beum Kim.

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Conflict of interest

K-HP, E-YC, Y-NC, H-YJ, J-SK and G-BK declare that they have no conflict of interest.

Ethical approval

This study had been approved by the Chonbuk National University informed consent was obtained from all individual participants included in the study. (Approval No: CBU2013-0910).

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Significance statement: This study discovers a potential therapeutic application of Ulmus davidiana extract for LPS-induced lung injury and liver function.

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Park, KH., Chung, EY., Choi, YN. et al. Oral administration of Ulmus davidiana extract suppresses interleukin-1β expression in LPS-induced immune responses and lung injury. Genes Genom 42, 87–95 (2020). https://doi.org/10.1007/s13258-019-00883-x

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  • DOI: https://doi.org/10.1007/s13258-019-00883-x

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