nach oben

Inflammopharmacology

Erschienen in:

08.05.2019 | Original Article

Zinc and iron complexes of oleanolic acid, (OA) attenuate allergic airway inflammation in rats

verfasst von: Adnan Jehangir, Muhammad Shahzad, Khadija Shahid, Akbar Waheed, Farhana Ayub

Erschienen in: Inflammopharmacology | Ausgabe 6/2019

Einloggen, um Zugang zu erhalten

Abstract

Oleanolic acid (OA) is a hydroxyl pentacyclic triterpene acid (HTAs) used in various ailments. Inflammatory diseases may be profoundly influenced by iron (Fe) and zinc (Zn) status. We studied the anti-asthmatic effects of two metal complexes (Fe and Zn) of OA in the ovalbumin (OVA)-induced rat model. Delayed type hypersensitivity (DTH) was measured. Total and differential leucocyte count was done in blood as well as bronchoalveolar lavage fluid (BALF). The mRNA expression levels of pro-inflammatory cytokines were measured in lung tissue by reverse transcription polymerase chain reaction. The levels of cyclooxygenase-2 (COX-2), immunoglobulin E (IgE) and 5-lipoxygenase (5-LOX) were estimated by enzyme linked immunosorbent assay. Splenocyte proliferation was performed through BrdU uptake method and nitric oxide levels were measured by colorimetric assay kit. The acute toxicity study was also done for the complexes. The asthmatic group developed allergic airway inflammation shown by increased DTH and inflammatory markers in blood and BALF. OA + Fe and OA + Zn displayed significant decrease in DTH, NO, expression of IL-4, 5, 13, 17, toll-like receptor-2, nuclear factor-kappa B and tumor necrosis factor-α; serum IgE, COX-2, and 5-LOX. The metal complexes also attenuated OVA-stimulated splenocyte proliferation. While no hepatotoxic or nephrotoxic potential was shown by OA + Fe and OA + Zn. Our findings indicate that both OA + Fe and OA + Zn possess significant anti-asthmatic effect which may be ascribed to its immunomodulatory and anti-inflammatory features.

Abbas AT, Abdel-Aziz MM, Zalata KR, Abd Al-Galel T-D (2005) Effect of dexamethasone and Nigella sativa on peripheral blood eosinophil count, IgG1 and IgG2a, cytokine profiles and lung inflammation in murine model of allergic asthma. Egypt J Immunol 12:95–102PubMed

Agrawal S, Agrawal A, Doughty B, Gerwitz A, Blenis J, van Dyke T, Pulendran B (2003) Cutting edge: different Toll-like receptor agonists instruct dendritic cells to induce distinct Th responses via differential modulation of extracellular signal-regulated kinase-mitogen-activated protein kinase and c-Fos. J Immunol 171:4984–4989PubMedCrossRef

Ashraf MI, Shahzad M, Shabbir A (2015) Oxyresveratrol ameliorates allergic airway inflammation via attenuation of IL-4, IL-5, and IL-13 expression levels. Cytokine 76:375–381PubMedCrossRef

Baker JF, Ghio AJ (2009) Iron homoeostasis in rheumatic disease. Rheumatology 48:1339–1344PubMedCrossRef

Batool A, Shahid K, Muddasir M (2015) Synthesis of aniline derivative of ursolic acid, its metal complexes, characterization and bioassay. Int J Pharm Sci Rev Res 30:25–32

Bijanzadeh M, Mahesh PA, Ramachandra NB (2011) An understanding of the genetic basis of asthma. Indian J Med Res 134:149–161PubMedPubMedCentral

Chakir J, Shannon J, Molet S, Fukakusa M, Elias J, Laviolette M, Boulet L-P, Hamid Q (2003) Airway remodeling-associated mediators in moderate to severe asthma: effect of steroids on TGF-β, IL-11, IL-17, and type I and type III collagen expression. J Allergy Clin Immunol 111:1293–1298PubMedCrossRef

Chauhan BF, Ducharme FM (2012) Anti-leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma in adults and children. Cochrane Database Syst Rev 5:2314

Chen S-X, Huang F-Y, Tan G-H, Wang C-C, Huang Y-H, Wang H, Zhou S-L, Chen F, Lin Y-Y, Liu J-B (2009) RNA interference against interleukin-5 attenuates airway inflammation and hyperresponsiveness in an asthma model. J Zhejiang Univ Sci B 10:22–28PubMedPubMedCentralCrossRef

Cheng J, Dackor RT, Bradbury JA, Li H, Degraff LM, Hong LK, King D, Lih FB, Gruzdev A, Edin ML, Travlos GS, Flake GP, Tomer KB, Zeldin DC (2016) Contribution of alveolar type II cell–derived cyclooxygenase-2 to basal airway function, lung inflammation, and lung fibrosis. FASEB J 30:160–173PubMedCrossRef

Cho JY, Miller M, Baek KJ, Han JW, Nayar J, Lee SY, McElwain K, McElwain S, Friedman S, Broide DH (2004) Inhibition of airway remodeling in IL-5–deficient mice. J Clin Investig 113:551–560PubMedCrossRefPubMedCentral

Diallo A, Eklu-Gadegkeku K, Agbono A, Aklikokou K, Creppy EE, Gbeassor M (2010) Acute and sub-chronic (28-day) oral toxicity studies of hydroalcohol leaf extract of Ageratum conyzoides L (Asteraceae). Trop J Pharm Res 9:463–467CrossRef

el Mezayen R, el Gazzar M, Nicolls MR, Marecki JC, Dreskin SC, Nomiyama H (2006) Effect of thymoquinone on cyclooxygenase expression and prostaglandin production in a mouse model of allergic airway inflammation. Immunol Lett 106:72–81PubMedCrossRef

Fang C, Li X, Liang H, Xue L, Liu L, Yang C, Gao G, Jiang X (2015) Downregulation of SUMF2 gene in ovalbumin-induced rat model of allergic inflammation. Int J Clin Exp Pathol 8:12053–12063PubMedPubMedCentral

Finkelman FD, Hogan SP, Hershey GK, Rothenberg ME, Wills-Karp M (2010) Importance of cytokines in murine allergic airway disease and human asthma. J Immunol 184:1663–1674PubMedCrossRef

Ghosh S, Erzurum SC (2012) Modulation of asthma pathogenesis by nitric oxide pathways and therapeutic opportunities. Drug Discov Today 9:e89–e94CrossRef

Gour N, Wills-Karp M (2015) IL-4 and IL-13 signaling in allergic airway disease. Cytokine 75:68–78PubMedPubMedCentralCrossRef

Hashimoto T, Akiyama K, Kobayashi N, Mori A (2005) Comparison of IL-17 production by helper T cells among atopic and nonatopic asthmatics and control subjects. Int Arch Allergy Immunol 137:51–54PubMedCrossRef

Heffern MC, Yamamoto N, Holbrook RJ, Eckermann AL, Meade TJ (2013) Cobalt derivatives as promising therapeutic agents. Curr Opin Chem Biol 17:189–196PubMedCrossRef

Hirshfeld A, Getachew A, Sidberry GK, Iannone R (2000) The harriet lane handbook: a manual for pediatric house officers, 15 edn

Hutchison S, Choo-Kang BSW, Bundick RV, Leishman AJ, Brewer JM, McInnes IB, Garside P (2008) Tumour necrosis factor-α blockade suppresses murine allergic airways inflammation. Clin Exp Immunol 151:114–122PubMedPubMedCentralCrossRef

Jee YK, Gilour J, Kelly A, Bowen H, Richards D, Soh C, Smith P, Hawrylowicz C, Cousins D, Lee T, Lavender P (2005) Repression of interleukin-5 transcription by the glucocorticoid receptor targets GATA3 signaling and involves histone deacetylase recruitment. J Biol Chem 280:23243–23250PubMedCrossRef

Jeon W-Y, Shin I-S, Shin H-K, Lee M-Y (2015) Samsoeum water extract attenuates allergic airway inflammation via modulation of Th1/Th2 cytokines and decrease of iNOS expression in asthmatic mice. BMC Complement Altern Med 15:47PubMedPubMedCentralCrossRef

Johnston SL, Martin RJ (2005) Chlamydophila pneumoniae and Mycoplasma pneumoniae: a role in asthma pathogenesis? Am J Respir Crit Care Med 172:1078–1089PubMedCrossRef

Kazani S, Arm JP, Boyce J, Chhay H, Dutile S, Wechsler ME, Govindarajulu U, Ivester P, Ainsworth HC, Sergeant S, Chilton FH, Israel E (2014) LTC(4) synthase polymorphism modifies efficacy of botanical seed oil combination in asthma. SpringerPlus 3:661PubMedPubMedCentralCrossRef

Keen JC, Sholl L, Wills-Karp M, Georas SN (2001) Preferential activation of nuclear factor of activated T cells c correlates with mouse strain susceptibility to allergic responses and interleukin-4 gene expression. Am J Respir Cell Mol Biol 24:58–65PubMedCrossRef

Khan AM, Shahzad M, Raza Asim M, Imran M, Shabbir A (2015) Zingiber officinale ameliorates allergic asthma via suppression of Th2-mediated immune response. Pharm Biol 53:359–367PubMedCrossRef

Kim S-H, Kim B-K, Lee Y-C (2011) Antiasthmatic effects of hesperidin, a potential Th2 cytokine antagonist, in a mouse model of allergic asthma. Mediat Inflamm 2011:485402

Kim S-H, Hong J-H, Lee Y-C (2013) Ursolic acid, a potential PPARγ agonist, suppresses ovalbumin-induced airway inflammation and Penh by down-regulating IL-5, IL-13, and IL-17 in a mouse model of allergic asthma. Eur J Pharmacol 701:131–143PubMedCrossRef

Kim H-W, Lim C-Y, Kim B-Y, Cho S-I (2014a) So-Cheong-Ryong-Tang, a herbal medicine, modulates inflammatory cell infiltration and prevents airway remodeling via regulation of interleukin-17 and GM-CSF in allergic asthma in mice. Pharmacogn Mag 10:S506PubMedPubMedCentralCrossRef

Kim S-H, Hong J-H, Lee Y-C (2014b) Oleanolic acid suppresses ovalbumin-induced airway inflammation and Th2-mediated allergic asthma by modulating the transcription factors T-bet, GATA-3, RORγt and Foxp3 in asthmatic mice. Int Immunopharmacol 18:311–324PubMedCrossRef

Kim SY, Park SM, Hwangbo M, Lee JR, Byun SH, Ku SK, Cho IJ, Kim SC, Jee SY, Park SJ (2017) Cheongsangbangpung-tang ameliorated the acute inflammatory response via the inhibition of NF-κB activation and MAPK phosphorylation. BMC Complement Altern Med 17:46PubMedPubMedCentralCrossRef

King EM, Holden NS, Gong W, Rider CF, Newton R (2009) Inhibition of NF-κB-dependent transcription by MKP-1: transcriptional repression by glucocorticoids occurring via p38 mapk. J Biol Chem 284:26803–26815PubMedPubMedCentralCrossRef

Kusemiju T, Yama O, Okanlawon A (2012) Effect of Carica papaya bark extract on oxidative stress parameters in testes of male albino rats. Int J Appl Res Nat Prod 4:1–6

Laan M, Prause O, Miyamoto M, Sjöstrand M, Hytönen A, Kaneko T, Lötvall J, Lindén A (2003) A role of GM-CSF in the accumulation of neutrophils in the airways caused by IL-17 and TNF-α. Eur Respir J 21:387–393PubMedCrossRef

Laitinen LA, Haahtela T, Vilkka V, Lee T, Spur BW (1993) Leukotriene E4 and granulocytic infiltration into asthmatic airways. Lancet 341:989–990PubMedCrossRef

Leckie MJ, Ten Brinke A, Khan J, Diamant Z, O’connor BJ, Walls CM, Mathur AK, Cowley HC, Chung KF, Djukanovic R, Hansel TT, HOLGATE ST, Sterk PJ, Barnes PJ (2000) Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 356:2144–2148PubMedCrossRef

Lee M, Kim S, Kwon O-K, Oh S-R, Lee H-K, Ahn K (2009) Anti-inflammatory and anti-asthmatic effects of resveratrol, a polyphenolic stilbene, in a mouse model of allergic asthma. Int Immunopharmacol 9:418–424PubMedCrossRef

Lee JY, Moon H, Kim CJ (2010) Effects of hydroxy pentacyclic triterpene acids from Forsythia viridissima on asthmatic responses to ovalbumin challenge in conscious guinea pigs. Biol Pharm Bull 33:230–237PubMedCrossRef

Legrand A, Fermor B, Fink C, Pisetsky DS, Weinberg JB, Vail TP, Guilak F (2001) Interleukin-1, tumor necrosis factor α, and interleukin-17 synergistically up-regulate nitric oxide and prostaglandin E2 production in explants of human osteoarthritic knee menisci. Arthritis Rheum 44:2078–2083PubMedCrossRef

Li X, Chen Q, Chu C, You H, Jin M, Zhao X, Zhu X, Zhou W, Ji W (2014) Ovalbumin-induced experimental allergic asthma is Toll-like receptor 2 dependent. Allergy Asthma Proc 35:e15–e20PubMedCrossRef

Liang C, Ding Y, Song SB, Kim JA, Cuong NM, Ma JY, Kim YH (2013) Oleanane-triterpenoids from Panax stipuleanatus inhibit NF-κB. J Ginseng Res 37:74–79PubMedPubMedCentralCrossRef

Lin C, Wen X, Sun H (2016) Oleanolic acid derivatives for pharmaceutical use: a patent review. Expert Opin Ther Patents 26:643–655CrossRef

Maazi H, Shirinbak S, Bloksma N, Nawijn MC, van Oosterhout AJM (2011) Iron administration reduces airway hyperreactivity and eosinophilia in a mouse model of allergic asthma. Clin Exp Immunol 166:80–86PubMedPubMedCentralCrossRef

Mali RG, Dhake AS (2011) A review on herbal antiasthmatics. Orient Pharm Exp Med 11:77–90PubMedPubMedCentralCrossRef

Masid-De-brito D, Queto T, Gaspar-Elsas MIC, Xavier-Elsas P (2014) Roles of 5-lipoxygenase and cysteinyl-leukotriene type 1 receptors in the hematological response to allergen challenge and its prevention by diethylcarbamazine in a murine model of asthma. Mediat Inflamm 2014:403970CrossRef

Menzies-Gow A, Flood-Page P, Robinson D, Kay A (2007) Effect of inhaled interleukin-5 on eosinophil progenitors in the bronchi and bone marrow of asthmatic and non-asthmatic volunteers. Clin Exp Allergy 37:1023–1032PubMedCrossRef

Molet S, Hamid Q, Davoineb F, Nutku E, Tahaa R, Pagé N, Olivenstein R, Elias J, Chakir J (2001) IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J Allergy Clin Immunol 108:430–438PubMedCrossRef

Montuschi P (2010) Role of leukotrienes and leukotriene modifiers in asthma. Pharmaceuticals 3:1792–1811PubMedPubMedCentralCrossRef

Nam H-S, Lee SY, Kim SJ, Kim JS, Kwon SS, Kim YK, Kim KH, Moon HS, Song JS, Park SH, Kim SC (2009) The soluble tumor necrosis factor-alpha receptor suppresses airway inflammation in a murine model of acute asthma. Yonsei Med J 50:569–575PubMedPubMedCentralCrossRef

Neamati A, Boskabady MH, Afshari JT, Hazrati SM, Rohani AH (2009) The effect of natural adjuvants on tracheal responsiveness and cell count in lung lavage of sensitized guinea pigs. Respirology 14:877–884PubMedCrossRef

Okoko I, Yama OE (2011) Cytoarchitectural variations in the ovary, oviduct and uterus following intra-gastric gavages of Abrus precatorius Linn in albino rats. Int J Morphol 29:1408–1413CrossRef

Palaniyandi S, Liu X, Periasamy S, Ma A, Tang J, Jenkins M, Tuo W, Song W, Keegan AD, Conrad DH, Zhu X (2015) Inhibition of CD23-mediated IgE transcytosis suppresses the initiation and development of allergic airway inflammation. Mucosal Immunol 8:1262–1274PubMedPubMedCentralCrossRef

Park GY, Christman JW (2006) Involvement of cyclooxygenase-2 and prostaglandins in the molecular pathogenesis of inflammatory lung diseases. Am J Physiol-Lung cell Mol Physiol 290:L797–L805PubMedCrossRef

Prado CM, Martins MA, Tibério IFLC (2011) Nitric oxide in asthma physiopathology. ISRN Allergy 2011:832560PubMedPubMedCentralCrossRef

Prasad AS (2014) Zinc is an antioxidant and anti-inflammatory agent: its role in human health. Front Nutr 1:14PubMedPubMedCentralCrossRef

Redecke V, Häcker H, Datta SK, Fermin A, Pitha PM, Broide DH, Raz E (2004) Cutting edge: activation of toll-like receptor 2 induces a Th2 immune response and promotes experimental asthma. J Immunol 172:2739PubMedCrossRef

Roa J, Morikawa H, Crawford L, Baatjes A, Duong M, Denburg JA (2007) The effects of montelukast on tissue inflammatory and bone marrow responses in murine experimental allergic rhinitis: interaction with interleukin-5 deficiency. Immunology 122:438–444PubMedPubMedCentralCrossRef

Shabbir A, Shahzad M, Ali A, Zia-Ur-rehman M (2014) Anti-arthritic activity of N′-[(2, 4-dihydroxyphenyl) methylidene]-2-(3, 4-dimethyl-5, 5-dioxidopyrazolo [4, 3-c][1, 2] benzothiazin-1 (4H)-yl) acetohydrazide. Eur J Pharmacol 738:263–272PubMedCrossRef

Shahzad M, Yang X, Raza Asim M, Sun Q, Han Y, Zhang F, Cao Y, Lu S (2009) Black seed oil ameliorates allergic airway inflammation by inhibiting T-cell proliferation in rats. Pulm Pharmacol Ther 22:37–43PubMedCrossRef

Shanmugam MK, Dai X, Kumar AP, Tan BKH, Sethi G, Bishayee A (2014) Oleanolic acid and its synthetic derivatives for the prevention and therapy of cancer: preclinical and clinical evidence. Cancer Lett 346:206–216PubMedPubMedCentralCrossRef

Shin D, Park S-H, Choi Y-J, Kim Y-H, Antika LD, Habibah NU, Kang M-K, Kang Y-H (2015) Dietary compound kaempferol inhibits airway thickening induced by allergic reaction in a bovine serum albumin-induced model of asthma. Int J Mol Sci 16:29980–29995PubMedPubMedCentralCrossRef

Shishodia S, Majumdar S, Banerjee S, Aggarwal BB (2003) Ursolic acid inhibits nuclear factor-κB activation induced by carcinogenic agents through suppression of IκBα kinase and p65 phosphorylation correlation with down-regulation of cyclooxygenase 2, matrix metalloproteinase 9, and cyclin D1. Cancer Res 63:4375–4383PubMed

Steinke JW, Borish L (2001) Th2 cytokines and asthma. Interleukin-4: its role in the pathogenesis of asthma, and targeting it for asthma treatment with interleukin-4 receptor antagonists. Respir Res 2:66PubMedPubMedCentralCrossRef

Takatsu K (2011) Interleukin-5 and IL-5 receptor in health and diseases. Proc Jpn Acad Ser B 87:463–485CrossRef

Thorburn AN, Tseng H-Y, Donovan C, Hansbro NG, Jarnicki AG, Foster PS, Gibson PG, Hansbro PM (2016) TLR2, TLR4 AND MyD88 mediate allergic airway disease (AAD) and Streptococcus pneumoniae-induced suppression of AAD. PLoS ONE 11:e0156402PubMedPubMedCentralCrossRef

Tian J, Zhu T, Liu J, Guo Z, Cao X (2015) Platelets promote allergic asthma through the expression of CD154. Cell Mol Immunol 12:700–707PubMedCrossRef

Toledo AC, Sakoda CPP, Perini A, Pinheiro NM, Magalhães RM, Grecco S, Tibério I, Câmara NO, Martins MA, Lago JHG, Prado CM (2013) Flavonone treatment reverses airway inflammation and remodelling in an asthma murine model. Br J Pharmacol 168:1736–1749PubMedPubMedCentralCrossRef

Trajkovic V, Stosic-Grujicic S, Samardzic T, Markovic M, Miljkovic D, Ramic Z, Stojkovic MM (2001) Interleukin-17 stimulates inducible nitric oxide synthase activation in rodent astrocytes. J Neuroimmunol 119:183–191PubMedCrossRef

Trezena AG, da Silva ZL, Oliveira-Filho RM, Damazo AS, Straus AH, Takahashi HK, Oliani SM, de Lima WT (2003) Differential regulation of the release of tumor necrosis factor-alpha and of eicosanoids by mast cells in rat airways after antigen challenge. Mediat Inflamm 12:237–246CrossRef

Yousef AM, Elmorsy E (2017) Serum zinc level in bronchial asthma. Egyptian J Chest Dis Tuberc 66:1–4CrossRef

Zaman K, Hanigan MH, Smith A, Vaughan J, Macdonald T, Jones DR, Hunt JF, Gaston B (2006) Endogenous S-nitrosoglutathione modifies 5-lipoxygenase expression in airway epithelial cells. Am J Respir Cell Mol Biol 34:387–393PubMedPubMedCentralCrossRef

Titel: Zinc and iron complexes of oleanolic acid, (OA) attenuate allergic airway inflammation in rats
verfasst von: Adnan Jehangir
Muhammad Shahzad
Khadija Shahid
Akbar Waheed
Farhana Ayub
Publikationsdatum: 08.05.2019
Verlag: Springer International Publishing
Erschienen in: Inflammopharmacology / Ausgabe 6/2019
Print ISSN: 0925-4692
Elektronische ISSN: 1568-5608
DOI: https://doi.org/10.1007/s10787-019-00597-2

Live-Webinar "Chronische Unterbauch- und Viszeralschmerzen in der Praxis managen"

Springer Medizin

Zinc and iron complexes of oleanolic acid, (OA) attenuate allergic airway inflammation in rats

Abstract

Live-Webinar "Chronische Unterbauch- und Viszeralschmerzen in der Praxis managen"

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 6/2019

The citrus flavanone naringenin attenuates zymosan-induced mouse joint inflammation: induction of Nrf2 expression in recruited CD45+ hematopoietic cells

Pterodontic acid isolated from Laggera pterodonta suppressed RIG-I/NF-KB/STAT1/Type I interferon and programmed death-ligand 1/2 activation induced by influenza A virus in vitro

Inflammatory responses bridge comorbid cardiac disorder in experimental model of IBD induced by DSS: protective effect of the trigonelline

The investigation of possible roles of central 5-HT7 receptors in antipyretic effect mechanism of paracetamol in LPS-induced hyperthermia model of mice

Preemptive meloxicam achieves a better effect on postoperative pain control and similar tolerance compared with postoperative meloxicam in patients receiving arthroscopic knee surgery

Anti-inflammatory and renal protective effect of gingerol in high-fat diet/streptozotocin-induced diabetic rats via inflammatory mechanism