Skip to main content
SpringerLink
Log in

Gallic acid ameliorates COPD-associated exacerbation in mice

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

COPD is an inflammatory lung disease, which is often exacerbated with microbial infections resulting in worsening of respiratory symptoms. Gallic acid (GA), a naturally occurring phenolic compound is known to possess anti-oxidant/anti-inflammatory activity. We have recently reported that GA protects against the elastase (ET) induced lung inflammation and emphysema and the present work was designed to investigate the beneficial effects of Gallic acid against ET + Lipopolysachharide (LPS) induced COPD exacerbation like condition in mice model. Our data showed that i.t. administration of LPS at 21 days after ET instillation resulted in significant infiltration of inflammatory cells particularly neutrophils (p < 0.0001) into the lungs along with elevated levels of pro-inflammatory cytokines like TNF-α, IL-1β and IL-6 (p < 0.0001). Interestingly, daily administration of GA (200 mg/Kg b. wt.) starting 7 days before ET instillation, significantly blunted the ET + LPS induced inflammation as indicated by reduced number of inflammatory cells particularly neutrophils (p < 0.0001) in BALF along with suppression of myeloperoxidase activity (p = 0.0009) and production of pro-inflammatory cytokines (p < 0.0001). Further, GA also restored the redox imbalance in the lungs towards normal. Additionally, phosphorylation of p65-NF-κB was found to be reduced (p = 0.015), which was associated with downregulation in the gene expression of IL-1β (p = 0.022) and TNF-α (p = 0.04). Conversely, GA treatment resulted in increased protein levels of Nrf2 (p = 0.021) with concomitant increase in transcription of its downstream target genes HO-1 (p = 0.033) and Prdx-1 (p = 0.006). Overall, our data show that GA effectively modulates COPD exacerbation manifestations in mice potentially by restoring redox imbalance in lungs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig.4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, Celli BR, Chen R, Decramer M, Fabbri LM, Frith P, Halpin DM, Lopez Varela MV, Nishimura M, Roche N, Rodriguez-Roisin R, Sin DD, Singh D, Stockley R, Vestbo J, Wedzicha JA, Agusti A (2017) Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017. Report GOLD executive summary. Am J Respir Crit Care Med 195(5):557–582. https://doi.org/10.1164/rccm201701-0218PP

    Article  CAS  PubMed  Google Scholar 

  2. Quaderi SA, Hurst JR (2018) The unmet global burden of COPD. Global Health Epidemiol Genomics 3:e4–e4. https://doi.org/10.1017/gheg.2018.1

    Article  CAS  Google Scholar 

  3. Viniol C, Vogelmeier CF (2018) Exacerbations of COPD. Eur Respir Rev 27(147):170103. https://doi.org/10.1183/16000617.0103-2017

    Article  PubMed  Google Scholar 

  4. Rubinsztajn R, Przybylowski T, Maskey-Warzechowska M, Karwat K, Chazan R (2016) Exacerbations of chronic obstructive pulmonary disease and quality of life of patients. Adv Exp Med Biol 884:69–74. https://doi.org/10.1007/5584_2015_178

    Article  CAS  PubMed  Google Scholar 

  5. Schmidt SAJ, Johansen MB, Olsen M, Xu X, Parker JM, Molfino NA, Lash TL, Sarensen HT, Christiansen CF (2014) The impact of exacerbation frequency on mortality following acute exacerbations of COPD: a registry-based cohort study. BMJ Open 4(12):e006720. https://doi.org/10.1136/bmjopen-2014-006720

    Article  PubMed  PubMed Central  Google Scholar 

  6. Bafadhel M, McKenna S, Terry S, Mistry V, Reid C, Haldar P, McCormick M, Haldar K, Kebadze T, Duvoix A, Lindblad K, Patel H, Rugman P, Dodson P, Jenkins M, Saunders M, Newbold P, Green RH, Venge P, Lomas DA, Barer MR, Johnston SL, Pavord ID, Brightling CE (2011) Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers. Am J Respir Crit Care Med 184(6):662–671. https://doi.org/10.1164/rccm.201104-0597OC

    Article  PubMed  Google Scholar 

  7. Sethi S, Evans N, Grant BJB, Murphy TF (2002) New strains of bacteria and exacerbations of chronic obstructive pulmonary disease. N Engl J Med 347(7):465–471. https://doi.org/10.1056/NEJMoa012561

    Article  PubMed  Google Scholar 

  8. Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S, Decramer M (2008) A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med 359(15):1543–1554

    Article  CAS  Google Scholar 

  9. Burge PS, Calverley PMA, Jones PW, Spencer S, Anderson JA, Maslen TK (2000) Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial. BMJ 320(7245):1297. https://doi.org/10.1136/bmj.320.7245.1297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Anthonisen NR, Connett JE, Kiley JP, Altose MD, Bailey WC, Buist AS, Conway WA Jr, Enright PL, Kanner RE, O'Hara P, Owens GR, Scanlon PD, Tashkin DP, Wise RA, Altose MD, Connors AF, Redline S, Deitz C, Rakos RF, Conway WA Jr, DeHorn A, Ward JC, Hoppe-Ryan CS, Jentons RL, Reddick JA, Sawicki C, Wise RA, Permutt S, Rand CS, Scanlon PD, Davis LJ, Hurt RD, Miller RD, Williams DE, Caron GM, Lauger GG, Toogood SM, Buist AS, Bjornson WM, Johnson LR, Bailey WC, Brooks CM, Dolce JJ, Higgins DM, Johnson MA, Lorish CD, Martin BA, Tashkin DP, Coulson AH, Gong H, Harber PI, Li VC, Roth M, Nides MA, Simmons MS, Zuniga I, Anthonisen NR, Manfreda J, Murray RP, Rempel-Rossum SC, Stoyko JM, Connett JE, Kjelsberg MO, Cowles MK, Durkin DA, Enright PL, Kurnow KJ, Lee WW, Lindgren PG, Mongin SJ, O'Hara P, Voelker HT, Waller LA, Owens GR, Rogers RM, Johnston JJ, Pope FP, Vitale FM, Kanner RE, Rigdon MA, Benton KC, Grant PM, Becklake M, Burrows B, Cleary P, Kimbel P, Nett L, Ockene JK, Senior RM, Snider GL, Spitzer W, Williams OD, Hurd SS, Kiley JP, Wu MC, Ayres SM, Hyatt RE, Mason BA (1994) Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1: the lung health study. JAMA 272(19):1497–1505. https://doi.org/10.1001/jama.1994.03520190043033

    Article  CAS  PubMed  Google Scholar 

  11. Drost EM, Skwarski KM, Sauleda J, Soler N, Roca J, Agusti A, MacNee W (2005) Oxidative stress and airway inflammation in severe exacerbations of COPD. Thorax 60(4):293–300. https://doi.org/10.1136/thx.2004.027946

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Caramori G, Romagnoli M, Casolari P, Bellettato C, Casoni G, Boschetto P, Chung KF, Barnes PJ, Adcock IM, Ciaccia A, Fabbri LM, Papi A (2003) Nuclear localisation of p65 in sputum macrophages but not in sputum neutrophils during COPD exacerbations. Thorax 58(4):348–351

    Article  CAS  Google Scholar 

  13. Yamada K, Asai K, Nagayasu F, Sato K, Ijiri N, Yoshii N, Imahashi Y, Watanabe T, Tochino Y, Kanazawa H, Hirata K (2016) Impaired nuclear factor erythroid 2-related factor 2 expression increases apoptosis of airway epithelial cells in patients with chronic obstructive pulmonary disease due to cigarette smoking. BMC Pulm Med 16(1):27. https://doi.org/10.1186/s12890-016-0189-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Badhani B, Sharma N, Kakkar R (2015) Gallic acid: a versatile antioxidant with promising therapeutic and industrial applications. RSC Adv 5(35):27540–27557. https://doi.org/10.1039/c5ra01911g

    Article  CAS  Google Scholar 

  15. Pandurangan AK, Mohebali N, Esa NM, Looi CY, Ismail S, Saadatdoust Z (2015) Gallic acid suppresses inflammation in dextran sodium sulfate-induced colitis in mice: possible mechanisms. Int Immunopharmacol 28(2):1034–1043. https://doi.org/10.1016/j.intimp.2015.08.019

    Article  CAS  PubMed  Google Scholar 

  16. Pandurangan AK, Mohebali N, Norhaizan ME, Looi CY (2015) Gallic acid attenuates dextran sulfate sodium-induced experimental colitis in BALB/c mice. Drug Design Dev Ther 9:3923–3934. https://doi.org/10.2147/dddt.s86345

    Article  CAS  Google Scholar 

  17. Zhu L, Gu P, Shen H (2019) Gallic acid improved inflammation via NF-kappaB pathway in TNBS-induced ulcerative colitis. Int Immunopharmacol 67:129–137. https://doi.org/10.1016/j.intimp.2018.11.049

    Article  CAS  PubMed  Google Scholar 

  18. Nikbakht J, Hemmati AA, Arzi A, Mansouri MT, Rezaie A, Ghafourian M (2015) Protective effect of gallic acid against bleomycin-induced pulmonary fibrosis in rats. Pharmacol Rep 67(6):1061–1067. https://doi.org/10.1016/j.pharep.2015.03.012

    Article  CAS  PubMed  Google Scholar 

  19. Singla E, Dharwal V, Naura AS (2020) Gallic acid protects against the COPD-linked lung inflammation and emphysema in mice. Inflamm Res 69(4):423–434. https://doi.org/10.1007/s00011-020-01333-1

    Article  CAS  PubMed  Google Scholar 

  20. Dransfield MT, Washko GR, Foreman MG, Estepar RS, Reilly J, Bailey WC (2007) Gender differences in the severity of CT emphysema in COPD. Chest 132(2):464–470. https://doi.org/10.1378/chest.07-0863

    Article  PubMed  Google Scholar 

  21. Puri G, Naura AS (2020) Critical role of mitochondrial oxidative stress in acid aspiration induced ALI in mice. Toxicol Mech Methods. https://doi.org/10.1080/15376516.2019.1710888

    Article  PubMed  Google Scholar 

  22. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275

    Article  CAS  Google Scholar 

  23. Suzuki K, Ota H, Sasagawa S, Sakatani T, Fujikura T (1983) Assay method for myeloperoxidase in human polymorphonuclear leukocytes. Anal Biochem 132(2):345–352. https://doi.org/10.1016/0003-2697(83)90019-2

    Article  CAS  PubMed  Google Scholar 

  24. Wang H, Joseph JA (1999) Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic Biol Med 27(5–6):612–616

    Article  CAS  Google Scholar 

  25. Moron MS, Depierre JW, Mannervik B (1979) Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta 582(1):67–78

    Article  CAS  Google Scholar 

  26. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95(2):351–358

    Article  CAS  Google Scholar 

  27. Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, Ahn BW, Shaltiel S, Stadtman ER (1990) Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 186:464–478

    Article  CAS  Google Scholar 

  28. Kono Y (1978) Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophys 186(1):189–195. https://doi.org/10.1016/0003-9861(78)90479-4

    Article  CAS  PubMed  Google Scholar 

  29. Luck H (1965) Catalase. Methods of enzymatic analysis. Elsevier, Amsterdam, pp 885–894

    Book  Google Scholar 

  30. Dharwal V, Naura AS (2018) PARP-1 inhibition ameliorates elastase induced lung inflammation and emphysema in mice. Biochem Pharmacol 150:24–34. https://doi.org/10.1016/j.bcp.2018.01.027

    Article  CAS  PubMed  Google Scholar 

  31. Sharma S, Sethi GS, Naura AS (2019) Curcumin ameliorates ovalbumin-induced atopic dermatitis and blocks the progression of atopic march in mice. Inflammation. https://doi.org/10.1007/s10753-019-01126-7

    Article  Google Scholar 

  32. Kobayashi S, Fujinawa R, Ota F, Angata T, Ueno M, Maeno T, Kitazume S, Yoshida K, Ishii T, Gao C, Ohtsubo K, Yamaguchi Y, Betsuyaku T, Kida K, Taniguchi N (2013) A single dose of lipopolysaccharide into mice with emphysema mimics human chronic obstructive pulmonary disease exacerbation as assessed by micro-computed tomography. Am J Respir Cell Mol Biol 49(6):971–977. https://doi.org/10.1165/rcmb2013-0074OC

    Article  CAS  PubMed  Google Scholar 

  33. Alberto P, Fabrizio L, Francesca F, Leonardo MF (2006) Pathophysiology of exacerbations of chronic obstructive pulmonary disease. Proc Am Thorac Soc 3(3):245–251. https://doi.org/10.1513/pats.200512-125SF

    Article  Google Scholar 

  34. Perng DW, Chen PK (2017) The relationship between airway inflammation and exacerbation in chronic obstructive pulmonary disease. Tuberc Respir Dis 80(4):325–335. https://doi.org/10.4046/trd.2017.0085

    Article  Google Scholar 

  35. Schuliga M (2015) NF-kappaB signaling in chronic inflammatory airway disease. Biomolecules 5(3):1266–1283. https://doi.org/10.3390/biom5031266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Liu T, Zhang L, Joo D, Sun SC (2017) NF-kB signaling in inflammation. Signal Transduct Target Ther 2:17023. https://doi.org/10.1038/sigtrans.2017.23

    Article  PubMed  PubMed Central  Google Scholar 

  37. Feng R-B, Wang Y, He C, Yang Y, Wan J-B (2018) Gallic acid, a natural polyphenol, protects against tert-butyl hydroperoxide- induced hepatotoxicity by activating ERK-Nrf2-Keap1-mediated antioxidative response. Food Chem Toxicol 119:479–488. https://doi.org/10.1016/j.fct.2017.10.033

    Article  CAS  PubMed  Google Scholar 

  38. Lee SH, Sohn DH, Jin XY, Kim SW, Choi SC, Seo GS (2007) 2',4',6'-tris(methoxymethoxy) chalcone protects against trinitrobenzene sulfonic acid-induced colitis and blocks tumor necrosis factor-alpha-induced intestinal epithelial inflammation via heme oxygenase 1-dependent and independent pathways. Biochem Pharmacol 74(6):870–880. https://doi.org/10.1016/j.bcp.2007.06.034

    Article  CAS  PubMed  Google Scholar 

  39. Bellezza I, Tucci A, Galli F, Grottelli S, Mierla AL, Pilolli F, Minelli A (2012) Inhibition of NF-kappaB nuclear translocation via HO-1 activation underlies alpha-tocopheryl succinate toxicity. J Nutr Biochem 23(12):1583–1591. https://doi.org/10.1016/j.jnutbio.2011.10.012

    Article  CAS  PubMed  Google Scholar 

  40. Zhu GF, Guo HJ, Huang Y, Wu CT, Zhang XF (2015) Eriodictyol, a plant flavonoid, attenuates LPS-induced acute lung injury through its antioxidative and anti-inflammatory activity. Exp Ther Med 10(6):2259–2266. https://doi.org/10.3892/etm.2015.2827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Lv H, Yu Z, Zheng Y, Wang L, Qin X, Cheng G, Ci X (2016) Isovitexin exerts anti-inflammatory and anti-oxidant activities on lipopolysaccharide-induced acute lung injury by inhibiting MAPK and NF-kappaB and activating HO-1/Nrf2 pathways. Int J Biol Sci 12(1):72–86. https://doi.org/10.7150/ijbs.13188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Tanaka M, Kishimoto Y, Sasaki M, Sato A, Kamiya T, Kondo K, Iida K (2018) Terminalia bellirica (Gaertn.) Roxb. Extract and gallic acid attenuate LPS-induced inflammation and oxidative stress via MAPK/NF-kB and Akt/AMPK/Nrf2 Pathways. Oxidat Med Cell Longev. https://doi.org/10.1155/2018/9364364

    Article  Google Scholar 

  43. Abdel-Moneim A, Yousef AI, Abd El-Twab SM, Abdel Reheim ES, Ashour MB (2017) Gallic acid and p-coumaric acid attenuate type 2 diabetes-induced neurodegeneration in rats. Metab Brain Dis 32(4):1279–1286. https://doi.org/10.1007/s11011-017-0039-8

    Article  CAS  PubMed  Google Scholar 

  44. Rasool MK, Sabina EP, Ramya SR, Preety P, Patel S, Mandal N, Mishra PP, Samuel J (2010) Hepatoprotective and antioxidant effects of gallic acid in paracetamol-induced liver damage in mice. J Pharm Pharmacol 62(5):638–643. https://doi.org/10.1211/jpp.62.05.0012

    Article  CAS  PubMed  Google Scholar 

  45. Mohamed HM, Abd El-Twab SM (2016) Gallic acid attenuates chromium-induced thyroid dysfunction by modulating antioxidant status and inflammatory cytokines. Environ Toxicol Pharmacol 48:225–236. https://doi.org/10.1016/j.etap.2016.08.019

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The present work was supported by funds from Department of Biotechnology, Government of India (BT/PR17968/MED/122/33/2016 and BT/RLF/Re-entry/36/2012) and UGC-SAP to ASN. We also acknowledge the Senior Research Fellowship to ES from ICMR, New Delhi, India.

Author information

Authors and Affiliations

  1. Department of Biochemistry, Panjab University, Chandigarh, 160014, India

    Esha Singla, Gayatri Puri, Vivek Dharwal & Amarjit S. Naura

Authors
  1. Esha Singla
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gayatri Puri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vivek Dharwal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Amarjit S. Naura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amarjit S. Naura.

Ethics declarations

Conflict of interest

The authors report no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Singla, E., Puri, G., Dharwal, V. et al. Gallic acid ameliorates COPD-associated exacerbation in mice. Mol Cell Biochem 476, 293–302 (2021). https://doi.org/10.1007/s11010-020-03905-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-020-03905-5

Keywords

Search

Navigation