Flavonoids as Cytokine Immunomodulators to Reduce Airway Inflammation via Inhibition of the NF‐κB Signalling Pathway: A Systematic Overview


Asthma is a chronic inflammatory respiratory disease with increasing prevalence which has been linked to the interaction of genetic and environmental factors. Specific types of infections and environmental exposure, alongside a predisposed set of genes, can lead to a systemic propensity for allergic T‐helper (Th) type 2 cells to induce cytokine responses, resulting in allergic airway inflammation. The key event in the pathogenesis of asthma is infiltration of inflammatory cells into the airways and lungs, resulting in mucus hypersecretion and intermittent obstructive events. Cytokines play a vital role in the pathogenesis of immune responses and also have a complex mode of action in inflammatory processes.

Peer‐reviewed articles investigating flavonoids with therapeutic evidence for the management of asthma were acquired from Pubmed, Embase, Scopus and Web of Science. We provide an extensive overview of the modulation of cytokines by flavonoids to assess how these natural products trigger immune responses, modulate immunity and lower airway inflammation.

Seventeen flavonoids were reported as cytokine modulators of nuclear transcription factor kappa B (NF‐κB) signalling in the identified articles. These flavonoids predominantly modulated the release of the production and expressions of the pro‐ and anti‐inflammatory cytokines TNF‐α, IL‐1β, IL‐8, Th17 (IL‐17), Th1 (IFN‐γ, IL‐2 and IL‐12) and Th2 (IL‐4, IL‐5, IL‐6 and IL‐13), inhibited eosinophil infiltration and decreased the activity and expression of NF‐κB.

Key Concepts

  • Bronchial asthma is a chronic inflammatory airway syndrome which endangers human health.
  • Corticosteroids and β2‐agonists are effective drugs for asthma; however, their prolonged use is associated with side effects such as drug tolerance, osteoporosis and immune suppression.
  • Asthma increases the number of inflammatory cells such as eosinophils and lymphocytes in peripheral blood, bronchoalveolar lavage fluid (BALF) and lung tissue and immunoglobulin E (IgE).
  • Flavonoids are plant‐derived active compounds reputed to have therapeutic potential.
  • The use of flavonoids in experimentally induced asthma models is associated with lower levels of Th2 cytokines such as IL‐4, IL‐5, IL‐6 and IL‐13 and modulation of pro‐inflammatory cytokines such as TNF‐α, IL‐1β and IL‐8.
  • Flavonoids generally inhibit pulmonary nuclear transcription factor kappa‐B (NF‐κB) or mitogen‐activated protein kinase (MAPK) signalling pathways and reduce airway inflammation in experimental models.
  • Flavonoids reduce airway hyperresponsiveness, mucus cell hyperplasia and fixed airway flow obstruction.
  • Flavonoids demonstrated significant in vitro and in vivo properties in animal models on homeostasis within the immune system and on the inflammatory response.

Keywords: asthma; cytokines; flavonoids; inflammation; NF‐κB

Figure 1. Chemical structures of flavonoids.
Figure 2. Immunomodulatory mechanisms of flavonoids that regulate Th1/Th2 cytokine balance via inhibition of NF‐κB, and which may have potential in the treatment of asthma.


Abuajah CI, Ogbonna AC and Osuji CM (2015) Functional components and medicinal properties of food: a review. Journal of Food Science and Technology 52 (5): 2522–2529.

Appleman LJ, Van Puijenbroek AA, Shu KM, et al. (2002) CD28 co stimulation mediates down‐regulation of p27kip1 and cell cycle progression by activation of the PI3K/PKB signalling pathway in primary human T cells. The Journal of Immunology 168 (6): 2729–2736.

Arola‐Arnal A, Cruz‐Carrión A, Torres‐Fuentes C, et al. (2019) Chrononutrition and polyphenols: roles and diseases. Nutrients 11 (11): E2602.

Athari SS (2019) Targeting cell signaling in allergic asthma. Signal Transduction and Targeted Therapy 4 (1): 45.

Baek JA, Lee YD and Lee CB (2009) Extracts of Magnoliae flos inhibit inducible nitric oxide synthase via ERK in human respiratory epithelial cells. Nitric Oxide 20 (2): 122–128.

Bang BR, Kwon HS, Kim SH, et al. (2014) Interleukin‐32γ suppresses allergic airway inflammation in mouse models of asthma. American Journal of Respiratory Cell and Molecular Biology 50 (6): 1021–1030.

Bao ZS, Hong L, Guan Y, et al. (2011) Inhibition of airway inflammation, hyperresponsiveness and remodeling by soy isoflavone in a murine model of allergic asthma. International Immunopharmacology 11 (8): 899–906.

Bergeron C, Al‐Ramli W and Hamid Q (2009) Remodeling in asthma. Proceedings of the American Thoracic Society 6 (3): 301–305.

Berry M, Brightling C, Pavord I, et al. (2007) TNF‐alpha in asthma. Current Opinion in Pharmacology 7 (3): 279–282.

Besnard AG, Guillou N, Tschopp J, et al. (2011) NLRP3 inflammasome is required in murine asthma in the absence of aluminum adjuvant. Allergy 66 (8): 1047–1057.

Birrell MA, McCluskie K, Wong S, et al. (2005) Resveratrol, an extract of red wine, inhibits lipopolysaccharide induced airway neutrophilia and inflammatory mediators through an NF‐κB‐independent mechanism. The FASEB Journal 19 (7): 1–22.

Birt DF, Hendrich S and Wang W (2001) Dietary agents in cancer prevention: flavonoids and isoflavonoids. Pharmacology and Therapeutics 90 (2‐3): 157–177.

Borish LC and Steinke JW (2003) Cytokines and chemokines. The Journal of Allergy and Clinical Immunology 111 (2): S460–S475.

Brewer JM, Conacher M, Hunter CA, et al. (1999) Aluminium hydroxide adjuvant initiates strong antigen‐specific Th2 responses in the absence of IL‐4 or IL‐13‐mediated signalling. The Journal of Immunology 163 (12): 6448–6454.

Bui TT, Piao CH, Song CH, et al. (2017a) Baicalein, wogonin, and Scutellaria baicalensis ethanol extract alleviate ovalbumin‐induced allergic airway inflammation and mast cell‐mediated anaphylactic shock by regulation of Th1/Th2 imbalance and histamine release. Anatomy & Cell Biology 50 (2): 124–134.

Bui TT, Piao CH, Song CH, et al. (2017b) Skullcapflavone II attenuates ovalbumin‐induced allergic rhinitis through the blocking of Th2 cytokine production and mast cell histamine release. International Immunopharmacology 52: 77–84.

Bush A, Fleming L and Saglani S (2017) Severe asthma in children. Respirology 22 (5): 886–897.

Busse W (2011) Asthma diagnosis and treatment: filling in the information gaps. Journal of Allergy and Clinical Immunology 128 (4): 740–750.

Caglayan‐Sozmen S, Karaman M, Cilaker‐Micili S, et al. (2016) Effects of quercetin treatment on epithelium‐derived cytokines and epithelial cell apoptosis in allergic airway inflammation mice model. Iranian Journal of Allergy, Asthma and Immunology 15 (6): 487–497.

Carter EP, Garat C and Imamura M (2004) Continual emerging roles of HO‐1: protection against airway inflammation. The American Journal of Physiology‐Lung Cellular and Molecular Physiology 287 (1): L24–L25.

Charles N, Watford WT, Ramos HL, et al. (2009) Lyn kinase controls basophil GATA‐3 transcription factor expression and induction of Th2 cell differentiation. Immunity 30 (41): 533–543.

Chen L, Cao H and Xiao J (2018) Polyphenols: Absorption, Bioavailability, and Metabolomics. In: Charis M Galanakis Polyphenols: Properties, Recovery, and Applications, pp 45–67. Woodhead Publishing.

Chen Y, Garvin LM, Nickola TJ, et al. (2014a) IL‐1beta induction of MUC5AC gene expression is mediated by CREB and NF‐kappaB and repressed by dexamethasone. The American Journal of Physiology‐Lung Cellular and Molecular Physiology 306 (8): L797–L807.

Chen Y, Wu H, Nie YC, et al. (2014b) Mucoactive effects of naringin in lipopolysaccharide‐induced acute lung injury mice and beagle dogs. Environmental Toxicology and Pharmacology 38 (1): 279–287.

Chen J, Zhou H, Wang J, et al. (2015) Therapeutic effects of resveratrol in a mouse model of HDM‐induced allergic asthma. International Immunopharmacology 25 (1): 43–48.

Chiruta C, Schubert D, Dargusch R, et al. (2012) Chemical modification of the multitarget neuroprotective compound fisetin. Journal of Medicinal Chemistry 55 (1): 378–389.

Cho IH, Gong JH and Kang MK (2014) Astragalin inhibits airway eotaxin‐1 induction and epithelial apoptosis through modulating oxidative stress‐responsive MAPK signaling. BMC Pulmonary Medicine 14: 122.

Choi YH, Jin GY, Guo HS, et al. (2012) Silibinin attenuates allergic airway inflammation in mice. Biochemical and Biophysical Research Communications 427 (3): 450–455.

Choi Y, Kim Y, Lee H, et al. (2019) Eosinophil extracellular traps activate type 2 innate lymphoid cells through stimulating airway epithelium in severe asthma. Allergy 75 (1): 95–103.

Chu X, Jiang L, Wei M, et al. (2013) Attenuation of allergic airway inflammation in a murine model of asthma by Licochalcone A. Immunopharmacology Immunotoxicology 35 (6): 653–661.

Coleman SL, Kruger MC, Sawyer GM, et al. (2016) Procyanidin A2 modulates IL‐4‐induced CCL26 production in human alveolar epithelial cells. International Journal of Molecular Sciences 17 (11): 1888.

Commins SP, Borish L and Steinke JW (2010) Immunologic messenger molecules: cytokines, interferons, and chemokines. Journal of Allergy and Clinical Immunology 125 (2): S53–S72.

Cortijo J, Mata M, Milara J, et al. (2011) Aclidinium inhibits cholinergic and tobacco smoke‐induced MUC5AC in human airways. European Respiratory Journal 37 (2): 244–254.

Cruz EA, Reuter S, Martin H, et al. (2012) Kalanchoe pinnata inhibits mast cell activation and prevents allergic airway disease. Phytomedicine 19 (2): 115–121.

Darnell JE, Jr‐Kerr IM and Stark GR (1994) Jak‐STAT pathways and transcriptional activation in response to IFNs and other extracellular signalling proteins. Science 264 (5164): 1415–1421.

Das M, Ram A and Ghosh B (2003) Luteolin alleviates bronchoconstriction and airway hyperreactivity in ovalbumin sensitized mice. Inflammation Research 52 (3): 101–106.

De Oliveira DR, Tintino SR, Bezerra MF, et al. (2015) In vitro antimicrobial and modulatory activity of the natural products silymarin and silibinin. BioMed Research International 2015: 292797.

Dechecchi MC, Nicolis E, Bezzerri V, et al. (2007) MPB‐07 reduces the inflammatory response to Pseudomonas aeruginosa in cystic fibrosis bronchial cells. American Journal of Respiratory Cell and Molecular Biology 36 (5): 615–624.

Deshpande DA, Wang WCH, McIlmoyle EL, et al. (2010) Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction. Nature Medicine 16 (11): 1299–1304.

Di‐Girolamo N, Indoh I, Jackson N, et al. (2006) Human mast cell‐derived gelatinase B (matrix metalloproteinase‐9) is regulated by inflammatory cytokines: role in cell migration. The Journal of Immunology 177 (4): 2638–2650.

Donnelly LE, Newton R, Kennedy GE, et al. (2004) Anti‐inflammatory effects of resveratrol in lung epithelial cells: molecular mechanisms. The American Journal of Physiology‐Lung Cellular and Molecular Physiology 287 (4): L774–L783.

Du Q, Gu X, Cai J, et al. (2012) Chrysin attenuates allergic airway inflammation by modulating the transcription factors T‐bet and GATA‐3 in mice. Molecular Medicine Reports 6 (1): 100–104.

Durrani SR, Viswanathan RK and Busse WW (2011) What effect does asthma treatment have on airway remodeling? Current perspectives. Journal of Allergy and Clinical Immunology 128 (3): 439–448.

Edwards MR, Bartlett NW, Clarke D, et al. (2009) Targeting the NF‐κB pathway in asthma and chronic obstructive pulmonary disease. Pharmacology & Therapeutics 121 (1): 1–13.

Elliott EI and Sutterwala FS (2015) Initiation and perpetuation of NLRP3 inflammasome activation and assembly. Immunological Reviews 265 (1): 35–52.

Fan SY, Zeng HW, Pei YH, et al. (2012) The anti‐inflammatory activities of an extract and compounds isolated from Platycladus orientalis (Linnaeus) Franco in vitro and ex vivo. Journal of Ethnopharmacology 141 (2): 647–652.

Farhadi F, Khameneh B, Iranshahi M, et al. (2019) Antibacterial activity of flavonoids and their structure‐activity relationship: an update review: antibacterial activity of flavonoids. Phytotherapy Research 33 (1): 13–40.

Farzaei MH, Singh AK, Kumar R, et al. (2019) Targeting inflammation by flavonoids: novel therapeutic strategy for metabolic disorders. International Journal of Molecular Sciences 20 (19): 4957.

Fernandes I, Pérez‐Gregorio R, Soares S, et al. (2017) Wine flavonoids in health and disease prevention. Molecules 22 (2): E292.

Franova S, Joskova M, Novakova E, et al. (2009) Effects of flavin7 on allergen induced hyperreactivity of airways. European Journal of Medical Research 14 (4): 78–81.

Franova S, Kazimierova I, Pappova L, et al. (2016) Bronchodilatory, antitussive and anti‐inflammatory effect of morin in the setting of experimentally induced allergic asthma. Journal of Pharmacy and Pharmacology 68 (8): 1064–1072.

Funaguchi N, Ohno Y, La BLB, et al. (2007) Narirutin inhibits airway inflammation in an allergic mouse model. Clinical and Experimental Pharmacology and Physiology 34 (8): 766–770.

Gagliardo R, Chanez P and Mathieu M (2003) Persistent activation of nuclear factor‐κB signaling pathway in severe uncontrolled asthma. American Journal of Respiratory and Critical Care Medicine 168 (10): 1190–1198.

Gao FA, Wei DB, Bian T, et al. (2012) Genistein attenuated allergic airway inflammation by modulating the transcription factors T‐bet, GATA‐3 and STAT‐6 in a murine model of asthma. Pharmacology 89 (3‐4): 229–236.

Gao P, Gibson PG, Baines KJ, et al. (2015) Anti‐inflammatory deficiencies in neutrophilic asthma: reduced galectin‐3 and IL‐1RA/IL‐1beta. Respiratory Research 16: 5.

Gerber BO, Zanni MP, Uguccioni M, et al. (1997) Functional expression of the eotaxin receptor CCR3 in T lymphocytes co‐localizing with eosinophils. Current Biology 7 (11): 836–843.

Gleich GJ (2000) Mechanisms of eosinophil‐associated inflammation. Jouranl of Allergy Clinical Immunology 105 (4): 651–663.

Goh FY, Upton N, Guan S, et al. (2012) Fisetin, a bioactive flavonol, attenuates allergic airway inflammation through negative regulation of NF‐κB. European Journal of Pharmacology 679 (1‐3): 109–116.

Gong JH, Shin D, Han SY, et al. (2012) Kaempferol suppresses eosionphil infiltration and airway inflammation in airway epithelial cells and in mice with allergic asthma. Journal of Nutrition 142 (1): 47–56.

Griffiths‐Johnson DA, Collins PD, Rossi AG, et al. (1993) The chemokine, eotaxin, activates guinea‐pig eosinophils in vitro and causes their accumulation into the lung in vivo. Biochemical and Biophysical Research Communications 197 (3): 1167–1172.

Gu X, Zhang Q, Du Q, et al. (2017) Pinocembrin attenuates allergic airway inflammation via inhibition of NF‐κB pathway in mice. International Immunopharmacology 53: 90–95.

Gueders MM, Bertholet P, Perin F, et al. (2008) A novel formulation of inhaled doxycycline reduces allergen‐induced inflammation, hyper‐responsiveness and remodelling by matrix metalloproteinases and cytokines modulation in a mouse model of asthma. Biochemical Pharmacology 75 (2): 514–526.

Guihua X, Shuyin L, Jinliang G, et al. (2016) Naringin protects ovalbumin‐induced airway inflammation in a mouse model of asthma. Inflammation 39 (2): 891–899.

Gupta K, Kumar S, Gupta RK, et al. (2016) Reversion of asthmatic complications and mast cell signalling pathways in BALB/c mice model using quercetin nanocrystals. Journal of Biomedical Nanotechnology 12 (4): 717–731.

Hart LA, Krishnan VL, Adcock IM, et al. (1998) Activation and localization of transcription factor, nuclear factor‐κB, in asthma. American Journal of Respiratory and Critical Care Medicine 158 (5): 1585–1592.

Harwood M, Danielewska‐Nikiel B, Borzelleca JF, et al. (2007) A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food and Chemical Toxicology 45 (11): 2179–2205.

Hashimoto S and Bel EH (2012) Current treatment of severe asthma. Clinical Experimental Allergy 42 (5): 693–705.

Heaney LG (2017) Cough and severe asthma. Pulmonary Pharmacology & Therapeutics 47: 72–76.

Heck S, Nguyen J, Le DD, et al. (2016) Pharmacological therapy of bronchial asthma: the role of biologicals. International Archives of Allergy and Immunology 168 (4): 241–252.

Heck S, Daubeuf F, Le DD, et al. (2018) Decreased migration of dendritic cells into the jugular‐Nodose Ganglia by the CXCL12 neutraligand chalcone 4 in ovalbumin‐sensitized asthmatic mice. Neuroimmunomodulation 24 (6): 331–340.

Henderson WR, Chi EY, Teo JL, et al. (2002) A small molecule inhibitor of redox‐regulated NF‐κB and activator protein‐1 transcription blocks allergic airway inflammation in a mouse asthma model. The Journal of Immunology 169 (9): 5294–5299.

Hernandez VH, Mackay GA, Lowell CA, et al. (2004) The Src kinase Lyn is a negative regulator of mast cell proliferation. Journal of Leukocyte Biology 75 (1): 143–151.

Herrick CA and Bottomly K (2003) To respond or not to respond: T cells in allergic asthma. Nature Reviews Immunology 3 (5): 405–412.

Holgate ST (2007) Epithelium dysfunction in asthma. The Journal of Allergy and Clinical Immunology 120 (6): 1233–1244.

Holt PG, Macaubas C, Stumbles PA, et al. (1999) The role of allergy in the development of asthma. Nature 402 (6760): B12–B17.

Huang W, Li ML, Xia MY, et al. (2018) Fisetin‐treatment alleviates airway inflammation through inhibition of MyD88/NF‐κB signaling pathway. International Journal of Molecular Medicine 42 (1): 208–218.

Hurst SM, McGhie TK, Cooney JM, et al. (2010) Blackcurrant proanthocyanidins augment IFN‐γ induced suppression of IL‐4 stimulated CCL26 secretion in alveolar epithelial cells. Molecular Nutrition & Food Research 54 (2): S159–S170.

Ito T, Connett JM, Kunkel SL, et al. (2012) Notch system in the linkage of innate and adaptive immunity. Journal of Leukocyte Biology 92 (1): 59–65.

Iwamura C, Shinoda K, Yoshimura M, et al. (2010) Naringenin chalcone suppresses allergic asthma by inhibiting the type‐2 function of CD4 T cells. Allergology International 59 (1): 67–73.

Jairaman A, Maguire CH, Schleimer RP, et al. (2016) Allergens stimulate store‐operated calcium entry and cytokine production in airway epithelial cells. Scientific Reports 6: 32311.

Jang HY, Ahn KS, Park MJ, et al. (2012) Skullcapflavone II inhibits ovalbumin‐induced airway inflammation in a mouse model of asthma. International Immunopharmacology 12 (4): 666–674.

Janssen‐Heininger YM, Poynter ME, et al. (2009) Nuclear factor kappa B, airway epithelium, and asthma: avenues for redox control. Proceedings of the American Thoracic Society 6 (3): 249–255.

Jayaprakasam B, Doddaga S, Wang R, et al. (2009) Licorice flavonoids inhibit eotaxin‐1 secretion by human fetal lung fibroblast in vitro. Journal of Agricultural and Food Chemistry 57 (3): 820–825.

Jeon JI, Ko SH, Kim YJ, et al. (2015) The flavone eupatilin inhibits eotaxin expression in an NF‐κB‐dependent and STAT6‐independent manner. Scandinavian Journal of Immunology 81 (3): 166–176.

Jung HW, Kang SY, Kang JS, et al. (2014) Effect of Kuwanon G isolated from the root bark of Morus alba on ovalbumin‐induced allergic response in a mouse model of asthma. Phytotherapy Research 28 (11): 1713–1719.

Kang JH, Kim BS, Uhm TG, et al. (2009) Gamma‐secretase inhibitor reduces allergic pulmonary inflammation by modulating Th1 and Th2 responses. American Journal of Respiratory and Critical Care Medicine 179 (10): 875–882.

Karin M and Mireille D (2000) The IκB kinase (IKK) and NF‐κB: key elements of proinflammatory signalling. In seminars in immunology. Elsevier 12 (1): 85–98.

Kew KM, Karner C, Mindus SM, et al. (2013) Combination formoterol and budesonide as maintenance and reliever therapy versus combination inhaler maintenance for chronic asthma in adults and children. Cochrane Database of Systematic Reviews 12: CD009019.

Khan WI, Blennerhasset P, Ma C, et al. (2001) STAT6 dependent goblet cell hyperplasia during intestinal nematode infection. Parasite Immunology 23 (1): 39–42.

Kim IB, Kim DY, Lee SJ, et al. (2006a) Inhibition of IL‐8 Production by green tea polyphenols in human nasal fibroblasts and A549 epithelial cells. Biological and Pharmaceutical Bulletin 29 (6): 1120–1125.

Kim SH, Park HJ, Leeb CM, et al. (2006b) Epigallocatechin‐3‐gallate protects toluene diisocyanate‐induced airway inflammation in a murine model of asthma. FEBS Letters 580 (7): 1883–1890.

Kim SH, Kim BK and Young‐Cheol L (2011) Antiasthmatic effects of hesperidin, a potential Th2 cytokine antagonist, in a mouse model of allergic asthma. Mediators of Inflammation 2011: 485402.

Kim SH, Saba E, Kim BK, et al. (2018) Luteolin attenuates airway inflammation by inducing the transition of CD4+CD25‐ to CD4+CD25+ regulatory T cells. European Journal of Pharmacology 820: 53–64.

Kim S, Song NJ, Chang SH, et al. (2019) Sulfuretin prevents obesity and metabolic diseases in diet induced obese mice. Biomolecules and Therapeutics 27 (1): 107–116.

King N, Helm R, Stanley JS, et al. (2005) Allergenic characteristics of a modified peanut allergen. Molecular Nutrition & Food Research 49 (10): 963–971.

Knobloch J, Sibbing B, Jungck D, et al. (2010) Resveratrol impairs the release of steroid‐resistant inflammatory cytokines from human airway smooth muscle cells in COPD. Journal of Pharmacology and Experimental Therapeutics 335 (3): 788–798.

Knobloch J, Hag H, Jungck D, et al. (2011) Resveratrol impairs the release of steroid‐resistant cytokines from bacterial endotoxin‐exposed alveolar macrophages in chronic obstructive pulmonary disease. Basic & Clinical Pharmacology & Toxicology 109 (2): 138–143.

Knobloch J, Wahl C, Feldmann M, et al. (2014) Resveratrol attenuates the release of inflammatory cytokines from human bronchial smooth muscle cells exposed to lipoteichoic acid in chronic obstructive pulmonary disease. Basic & Clinical Pharmacology & Toxicology 114 (2): 202–209.

Ko JW, Shin NR, Park SH, et al. (2017) Silibinin inhibits the fibrotic responses induced by cigarette smoke via suppression of TGF‐β1/Smad 2/3 signaling. Food and Chemical Toxicology 106: 424–429.

Komaravelli N, Kelley JP, Garofalo MP, et al. (2015) Role of dietary antioxidants in human meta pneumovirus infection. Virus Research 200: 19–23.

Kong YJ, Sun WX, Zhang YM, et al. (2008) Relationships between the expressions of intercellular adhesion molecule‐1 and tissue inhibitor of metalloproteinase‐1 and matrix metalloproteinase‐9 in lung tissues of patients with chronic obstructive pulmonary disease. Chinese Journal of Tuberculosis and Respiratory Diseases 31 (2): 129–133.

Kudo M, Ishigatsubo Y and Aoki I (2013) Pathology of asthma. Frontiers in Microbiology 10 (4): 263.

Kuperman DA, Huang X, Koth LL, et al. (2002) Direct effects of interleukin‐13 on epithelial cells cause airway hyper reactivity and mucus overproduction in asthma. Nature Medicine 8 (8): 885–889.

Kwon SH, Nam JI, Kim SH, et al. (2009) Kaempferol and quercetin, essential ingredients in Ginkgo biloba extract, inhibit interleukin‐1b‐induced MUC5AC gene expression in human airway epithelial cells. Phytotherapy Research 23 (12): 1708–1712.

Kyriakis JM and Avruch J (2012) Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10‐year update. Physiological Reviews 92 (2): 689–737.

Laky K and Fowlkes BJ (2008) Notch signaling in CD4 and CD8 T cell development. Current Opinion in Immunology 20 (2): 197–202.

Lam D, Ng N, Lee S, et al. (2008) Airway house dust extract exposures modify allergen‐induced airway hypersensitivity responses by TLR4‐dependent and independent pathways. Journal of Immunology 181 (4): 2925–2932.

Lee M, Kim S, Kwon OK, et al. (2009) Anti‐inflammatory and anti‐asthmatic effects of resveratrol, a polyphenolic stilbene in a mouse model of allergic asthma. International Immunopharmacology 9 (4): 418–424.

Lee FP, Shih CM, Shen HY, et al. (2010) Ayanin, a non‐selective phosphodiesterase 1–4 inhibitor, effectively suppresses ovalbumin‐induced airway hyperresponsiveness without affecting xylazine/ketamine‐induced anesthesia. European Journal of Pharmacology 635 (1‐3): 198–203.

Lee IC, Kim SH, Shin IS, et al. (2012a) Protective effects of pine bark extract on hexavalent chromium induced dermatoxicity in rats. Phytotherapy Research 26 (10): 1534–1540.

Lee T, Kwon HS, Bang BR, et al. (2012b) Grape seed proanthocyanidin extract attenuates allergic inflammation in murine models of asthma. Journal of Clinical & Experimental Immunology. 32 (6): 1292–1304.

Lee YH, Seo EK and Lee ST (2019) Skullcapflavone II Inhibits degradation of type I collagen by suppressing MMP‐1 transcription in human skin fibroblasts. International Journal of Molecular Sciences 20 (11): 2734–2749.

Leyva‐López N, Gutierrez‐Grijalva E, Ambriz‐Perez D, et al. (2016) Flavonoids as cytokine modulators: a possible therapy for inflammation‐related diseases. International Journal of Molecular Sciences 17 (6): E921.

Li B, Duan X, Xu C, et al. (2014a) Icariin attenuates glucocorticoid insensitivity mediated by repeated psychosocial stress on an ovalbumin‐induced murine model of asthma. International Immunopharmacology 19 (2): 381–390.

Li X, Chen Q and Chu C (2014b) Ovalbumin‐induced experimental allergic asthma is Toll‐like receptor 2 dependent. Allergy & Asthma Proceedings 35 (2): e15–e20.

Li D, Hu J, Wang T, et al. (2016) Silymarin attenuates cigarette smoke extract‐induced inflammation via simultaneous inhibition of autophagy and ERK/p38 MAPK pathway in human bronchial epithelial cells. Scientific Reports 6: 37751.

Li Y, Yu Q, Zhao W, et al. (2017) Oligomeric proanthocyanidins attenuate airway inflammation in asthma by inhibiting dendritic cells maturation. Molecular Immunology 91: 209–217.

Liang OD, Kleibrink BE, Schuette‐Nuetgen K, et al. (2011) Green tea epigallo‐catechin‐galleate ameliorates the development of obliterative airway disease. Experimental Lung Research 37 (7): 435–444.

Lim HJ, Jin HG, Woo ER, et al. (2013) The root barks of Morus alba and the flavonoid constituents inhibit airway inflammation. Journal of Ethnopharmacology 149 (1): 169–175.

Lim H, Heo MY and Kim HP (2019) Flavonoids: broad spectrum agents on chronic inflammation. Biomolecules and Therapeutics 27 (3): 241–253.

Lin Y, Tan D, Kan Q, et al. (2018) The protective effect of naringenin on airway remodeling after Mycoplasma Pneumoniae infection by inhibiting autophagy‐mediated lung inflammation and fibrosis. Mediators of Inflammation 2018: 8753894.

Liou CJ, Len WB, Wu SJ, et al. (2014) Casticin inhibits COX‐2 and iNOS expression via suppression of NF‐κB and MAPK signalling in lipopolysaccharide‐stimulated mouse macrophages. Journal of Ethnopharmacology 158 (Pt A): 310–316.

Liu H, Ren J, Chen H, et al. (2014) Resveratrol protects against cigarette smoke‐induced oxidative damage and pulmonary inflammation. Journal of Biochemical and Molecular Toxicology 28 (10): 465–471.

Liu C, Yang N, Song Y, et al. (2015a) Ganoderic acid C1 isolated from the anti‐asthma formula, ASHMI™ suppresses TNF‐α production by mouse macrophages and peripheral blood mononuclear cells from asthma patients. International Immunopharmacology 27 (2): 224–231.

Liu YN, Zha WJ, Ma Y, et al. (2015b) Galangin attenuates airway remodelling by inhibiting TGF‐β1‐mediated ROS generation and MAPK/Akt phosphorylation in asthma. Scientific Report 5: 11758.

Liu J, Wei Y, Luo Q, et al. (2016a) Baicalin attenuates inflammation in mice with OVA‐induced asthma by inhibiting NF‐κB and suppressing CCR7/CCL19/CCL21. International Journal of Molecular Medicine 38 (5): 1541–1548.

Liu X, Yu D and Wang T (2016b) Sappanone A attenuates allergic airway inflammation in ovalbumin‐induced asthma. International Archives of Allergy and Immunology 170 (3): 180–186.

Liu XJ, Bao HR, Zeng XL, et al. (2016c) Effects of resveratrol and genistein on nuclear factor κB, tumor necrosis factor α and matrix metalloproteinase 9 in patients with chronic obstructive pulmonary disease. Molecular Medicine Reports 13 (5): 4266–4272.

Liu Z, Han B, Chen X, et al. (2016d) Pycnogenol ameliorates asthmatic airway inflammation and inhibits the function of goblet Cells. DNA and Cell Biology 35 (11): 730–739.

Liu LL, Li FH, Zhang Y, et al. (2017) Tangeretin has anti‐asthmatic effects via regulating PI3K and Notch signaling and modulating Th1/Th2/Th17 cytokine balance in neonatal asthmatic mice. Brazilian Journal of Medical and Biological Research 50 (8): e5991.

Lukacs NW (2001) Role of chemokines in the pathogenesis of asthma. Nature Reviews Immunology 1 (2): 108–116.

Luo YL, Zhang CC, Li PB, et al. (2012) Naringin attenuates enhanced cough, airway hyperresponsiveness and airway inflammation in a guinea pig model of chronic bronchitis induced by cigarette smoke. International Immunopharmacology 13 (3): 301–307.

Luo J, Dong B and Wang K (2017) Baicalin inhibits biofilm formation, attenuates the quorum sensing‐controlled virulence and enhances Pseudomonas aeruginosa clearance in a mouse peritoneal implant infection model. Plos One 12 (4): e0176883.

Ma Y, Ge A, Zhu W, et al. (2016) Morin attenuates ovalbumin‐induced airway inflammation by modulating oxidative stress‐responsive MAPK signaling. Oxidative Medicine and Cellular Longevity 2016: 58436722016.

Mabalirajan U, Ahmad T, Rehman R, et al. (2013) Baicalein reduces airway injury in allergen and IL‐13 induced airway inflammation. PLoS One 8 (4): e62916.

Malcomson B, Wilson H, Veglia E, et al. (2016) Connectivity mapping (ssCMap) to predict A20‐inducing drugs and their anti‐inflammatory action in cystic fibrosis. Proceedings of the National Academy of Sciences USA 113 (26): E3725–E3734.

Maleki SJ, Crespo JF and Cabanillas B (2019) Anti‐inflammatory effects of flavonoids. Food Chemistry 299: 125124.

Mahmoud AM, Hernández Bautista RJ, Sandhu MA, et al. (2019) Beneficial effects of Citrus flavonoids on cardiovascular and metabolic health. Oxidative Medicine and Cellular Longevity 2019: 1–19.

Martin RA, Ather JL, Lundblad LK, et al. (2013) Interleukin‐1 receptor and caspase‐1 are required for the Th17 response in nitrogen dioxide‐promoted allergic airway disease. American Journal of Respiratory Cell and Molecular Biology 48 (5): 655–664.

Martinez FD and Vercelli D (2013) Asthma. Lancet 382 (9901): 1360–1372.

Medeiros KCP, Faustino L and Borduchi E (2009) Preventive and curative glycoside kaempferol treatments attenuate the TH2‐driven allergic airway disease. International Immunopharmacology 9 (13‐14): 1540–1548.

Mishra V, Banga J and Silveyra P (2018) Oxidative stress and cellular pathways of asthma and inflammation: therapeutic strategies and pharmacological targets. Pharmacology & Therapeutics 181: 169–182.

Moon H, Choi HH, Lee JY, et al. (2008) Quercetin inhalation inhibits the asthmatic responses by exposure to aerosolized‐ovalbumin in conscious guinea‐pigs. Archives of Pharmacal Research 31 (6): 771–778.

Mosmann TR and Moore KW (1991) The role of IL‐10 in cross regulation of Th1 and Th2 responses. Immunology Today 12 (3): A49–A53.

Mullane K (2011) The increasing challenge of discovering asthma drugs. Biochemical Pharmacology 82 (6): 586–599.

Nanua S, Zick SM, Andrade JE, et al. (2006) Quercetin blocks airway epithelial cell chemokine expression. American Journal of Respiratory Cell and Molecular Biology 35 (5): 602–610.

Nishizumi H and Yamamto T (1997) Impaired tyrosine phosphorylation and Ca2+ mobilization, but not degranulation, in lyn‐deficient bone marrow‐derived mast cells. The Journal of Immunology 1 (5): 2350–2355.

Oh CK, Geba GP and Molfino N (2010) Investigational therapeutics targeting the IL‐4/IL‐13/STAT‐6 pathway for the treatment of asthma. European Respiratory Review 19 (115): 46–54.

Oliveira TT, Campos KM, Cerqueira‐Lima AT, et al. (2015) Potential therapeutic effect of Allium cepa L. and quercetin in a murine model of Blomia tropicalis induced asthma. DARU Journal of Pharmaceutical Sciences 23: 18.

Papi A, Contoli M, Adcock IM, et al. (2013) Rhinovirus infection causes steroid resistance in airway epithelium through nuclear factor kappa B and c‐Jun N‐terminal kinase activation. Journal of Allergy and Clinical Immunolology 132 (5): 1075–1085.

Park SJ, Shin WH, Seo JW, et al. (2007) Anthocyanins inhibit airway inflammation and hyperresponsiveness in a murine asthma model. Food and Chemical Toxicology 45 (8): 1459–1467.

Park H, Lee CM, Jung ID, et al. (2009) Quercetin regulates Th1/Th2 balance in a murine model of asthma. International Immunopharmacology 9 (3): 261–267.

Park JY, Han X, Piao MJ, et al. (2016) Hyperoside induces endogenous antioxidant system to alleviate oxidative stress. Journal of Cancer Prevention 21 (1): 41–47.

Pease JE and Williams TJ (2001) Eotaxin and asthma. Current Opinion in Immunology 3: 248–253.

Peng HL, Huang WC, Cheng SC, et al. (2018) Fisetin inhibits the generation of inflammatory mediators in interleukin‐1β‐induced human lung epithelial cells by suppressing the NF‐κB and ERK1/2 pathways. International Immunopharmacology 60: 202–210.

Pérez‐Cano F and Castell M (2016) Flavonoids, inflammation and immune System. Nutrients 8 (10): 659.

Pietta PG (2000) Flavonoids as antioxidants. Journal of Natural Products 63 (7): 1035–1042.

Ponath PD, Qin S, Ringler DJ, et al. (1996) Cloning of the human eosinophil chemoattractant, eotaxin. Expression, receptor binding, and functional properties suggest a mechanism for the selective recruitment of eosinophils. Journal of Clinical Investigation 97 (3): 604–612.

Poynter ME, Irvin CG and Janssen‐Heininger YM (2002) Rapid activation of NF‐κB in airway epithelium in a murine model of allergic airway inflammation. The American Journal of Pathology 160 (4): 325–1334.

Poynter ME, Irvin CG and Janssen‐Heininger YM (2003) A prominent role for airway epithelial NF‐κB activation in lipopolysaccharide‐induced airway inflammation. Journal of Immunology 170 (12): 6257–6265.

Poynter ME, Cloots R, van Woerkom T, et al. (2004) NF‐κB activation in airways modulates allergic inflammation but not hyper responsiveness. Journal of Immunology 173 (11): 7003–7009.

Prado CM, Leick‐Maldonado EA, Yano L, et al. (2006) Effects of nitric oxide synthase in chronic allergic airway inflammation and remodelling. American Journal of Respiratory Cell and Molecular Biology 35: 457–465.

Quinton LJ, Jones MR, Simms BT, et al. (2007) Functions and regulation of NF‐κB RelA during pneumococcal pneumonia. Journal of Immunology 178 (3): 1896–1903.

Rab A, Rowe SM, Raju SV, et al. (2013) Cigarette smoke and CFTR: implications in the pathogenesis of COPD. American Journal of Physiology‐Lung Cellular and Molecular Physiology 305 (8): L530eL541.

Raby BA, Steen KV, Lazarus R, et al. (2006) Eotaxin polymorphisms and serum total IgE levels in children with asthma. Journal of Allergy and Clinical Immunology 117 (2): 298–305.

Rajajendram R, Tham CL, Akhtar MN, et al. (2015) Inhibition of epithelial CC‐family chemokine synthesis by the synthetic chalcone DMPF‐1 via disruption of NF‐κB nuclear translocation and suppression of experimental asthma in mice. Mediators of Inflammation 2015: 176926.

Rangasamy T, Guo J, Mitzner WA, et al. (2005) Disruption of Nrf2 enhances susceptibility to severe airway inflammation and asthma in mice. Journal of Experiment Medicine 202 (1): 47–59.

Rasul A, Millimouno FM, Eltayb WA, et al. (2013) Pinocembrin: a novel natural compound with versatile pharmacological and biological activities. Biomed Research International 2013 (2013): 379850.

Raval CM and Lee PJ (2010) Heme oxygenase‐1 in lung disease. Current Drug Targets 11 (12): 1532–1540.

Rice JB, White AG, Scarpati LM, et al. (2017) Long‐term systemic corticosteroid exposure: a systematic literature review. Clinical Therapeutics 39 (11): 2216–2229.

Robinett KS, Koziol‐White CJ, Akoluk A, et al. (2014) Bitter taste receptor function in asthmatic and non‐asthmatic human airway smooth muscle cells. American Journal of Respiratory Cell and Molecular Biology 50 (4): 678–683.

Rogerio AP, Kanashiro A, Fontanari C, et al. (2007) Anti‐inflammatory activity of quercetin and isoquercitrin in experimental murine allergic asthma. Inflammation Research 56 (10): 402–408.

Ryter SW, Kim HP, Nakahira K, et al. (2007) Protective functions of heme oxygenase‐1 and carbon monoxide in the respiratory system. Antioxidants & Redox Signaling 9 (12): 2157–2173.

Sallusto F, Mackay CR and Lanzavecchia A (1997) A selective expression of the eotaxin receptor CCR3 by human T helper 2 cells. Science 277 (5334): 2005–2007.

Samanta K, Bakowski D and Parekh AB (2014) Key role for store‐operated Ca2+ channels in activating gene expression in human airway bronchial epithelial cells. PLoS One 9 (8): e105586.

Schroder K and Tschopp J (2010) The inflammasomes. Cell 140 (6): 821–832.

Schuliga M (2015) NF‐kappa B signalling in chronic inflammatory airway disease. Biomolecules 5 (3): 1266–1283.

Sebastian RS, Wilkinson‐Enns C, Goldman JD, et al. (2015) A new database facilitates characterization of flavonoid intake, sources, and positive associations with diet quality among US adults. Journal of Nutrition 145 (6): 1239–1248.

Sergejeva S, Ivanov S, Lotvall J, et al. (2005) IL‐17 as a recruitment and survival factor for airway macrophages in allergic airway inflammation. American Journal of Respiratory Cell and Molecular Biology 33 (3): 248–253.

Shan L, Kang X, Liu F, et al. (2018) Epigallocatechin gallate improves airway inflammation through TGF‐β1 signalling pathway in asthmatic mice. Molecular Medicine Reports 18 (2): 2088–2096.

Shaw OM, Nyanhanda T, McGhie TK, et al. (2016) Blackcurrant anthocyanins modulate CCL11 secretion and suppress allergic airway inflammation. Molecular Nutrition & Food Research 61 (9): 1600868.

Shi Y and Massague J (2003) Mechanisms of TGF‐beta signaling from cell membrane to the nucleus. Cell 113 (6): 685–700.

Shi Y, Dai J, Liu H, et al. (2009) Naringenin inhibits allergen‐induced airway inflammation and airway responsiveness and inhibits NF‐kappaB activity in a murine model of asthma. Canadian Journal of Physiology and Pharmacology 87 (9): 729–735.

Shi Y, Tan Y, Mao S, et al. (2014) Naringenin inhibits allergen induced airway remodelling in a murine model of asthma. Molecular Medicine Reports 9 (4): 1204–1208.

Shimizu T, Lin F, Hasegawa M, et al. (2012) The potential bioproduction of the pharmaceutical agent sakuranetin, a flavonoid phytoalexin in rice. Bioengineered 3 (6): 352–357.

Shin IS, Shin NR, Jeon CM, et al. (2013) Inhibitory effects of Pycnogenol® (French maritime pine bark extract) on airway inflammation in ovalbumin‐induced allergic asthma. Food and Chemical Toxicology 62: 681–686.

Song MY, Jeong GS, Lee HS, et al. (2010) Sulfuretin attenuates allergic airway inflammation in mice. Biochemical and Biophysical Research Communications 400 (1): 83–88.

Steenwinckel V, Louahed J, Lemaire MM, et al. (2009) IL‐9 promotes IL‐13‐dependent paneth cell hyperplasia and up‐regulation of innate immunity mediators in intestinal mucosa. The Journal of Immunology 182 (8): 4737–4743.

Sun J, Li L, Wu J, et al. (2013) Effects of baicalin on airway remodelling in asthmatic mice. Planta Medica 79 (3‐4): 199–206.

Sung HC, Liang CJ, Lee CW, et al. (2015) The protective effect of eupafolin against TNF‐α‐induced lung inflammation via the reduction of intercellular cell adhesion molecule‐1 expression. Journal of Ethnopharmacology 170: 136–147.

Sutterwala FS, Ogura Y, Szczepanik M, et al. (2006) Critical role for NALP3/CIAS1/Cryopyrin in innate and adaptive immunity through its regulation of caspase‐1. Immunity 24 (3): 317–327.

Tak PP and Firestein GS (2001) NF‐κB: a key role in inflammatory diseases. Journal of Clinical Investigation 107 (1): 7–11.

Takeda M, Ito W, Tanabe M, et al. (2010) The pathophysiological roles of PI3Ks and therapeutic potential of selective inhibitors in allergic inflammation. International Archives of Allergy and Immunology 152 (1): 90–95.

Toledo AC, Sakoda CP, Perini A, et al. (2013) Flavonone treatment reverses airway inflammation and remodelling in an asthma murine model. British Journal of Pharmacology 168 (7): 1736–1749.

Tully JE, Hoffman SM, Lahue KG, et al. (2013) Epithelial NF‐κB orchestrates house dust mite‐induced airway inflammation, hyperresponsiveness, and fibrotic remodeling. Journal of Immunology 191 (12): 5811–5821.

Wang H, Guo Y, Guo Y, et al. (2013) An estrogen receptor dependent mechanism of oroxylin A in the repression of inflammatory response. Plos One 8 (7): 1–7.

Wang HH, Hsieh HL and Yang CM (2011) Nitric oxide production by endothelin‐1 enhances astrocytic migration via the tyrosine nitration of matrix metalloproteinase‐9. Journal of Cellular Physiolology 226 (9): 2244–2256.

Wang J, Zhang T, Ma C, et al. (2015) Puerarin attenuates airway inflammation by regulation of eotaxin‐3. Immunology Letters 163 (2): 173–178.

Wang H, Yang T, Wang T, et al. (2018) Phloretin attenuates mucus hypersecretion and airway inflammation induced by cigarette smoke. International Immunopharmacology 55: 112–119.

Wardlaw AJ, Dunnette S, Gleich GJ, et al. (1988) Eosinophils and mast cells in bronchoalveolar lavage in subjects with mild asthma. Relationship to bronchial hyper reactivity. American Review of Respiratory Disease 137 (1): 62–69.

Wei J, Bhatt S, Chang LM, et al. (2012a) Isoflavones, genistein and daidzein, regulate mucosal immune response by suppressing dendritic cell function. Plos One 7 (10): e47979.

Wei D, Ci X, Chu X, et al. (2012b) Hesperidin suppresses ovalbumin‐induced airway inflammation in a mouse allergic asthma model. Inflammation 35 (1): 114–121.

Wei Y, Liu B, Sun J, et al. (2015) Regulation of Th17/Treg function contributes to the attenuation of chronic airway inflammation by icariin in ovalbumin‐induced murine asthma model. Immunobiology 220 (6): 789–797.

Wenzel SE (2012) Asthma phenotypes: the evolution from clinical to molecular approaches. Nature Medicine 18 (5): 716–725.

Wills‐Karp M (1999) Immunologic basis of antigen‐induced airway hyperresponsiveness. Annual Review of Immunology 17: 255–281.

Willingham SB, Allen IC, Bergstralh DT, et al. (2009) NLRP3 (NALP3, Cryopyrin) facilitates in vivo caspase‐1 activation, necrosis, and HMGB1 release via inflammasome‐dependent and ‐independent pathways. The Journal of Immunology 183 (3): 2008–2015.

Wu YQ, Zhou CH, Tao J, et al. (2006) Antagonistic effects of nobiletin, a polymethoxyflavonoid, on eosinophilic airway inflammation of asthmatic rats and relevant mechanisms. Life Sciences 78 (23): 2689–2696.

Wu MY, Hung SK and Fu SL (2011) Immunosuppressive effects of fisetin in ovalbumin‐induced asthma through inhibition of NF‐κB activity. Journal of Agricultural and Food Chemistry 59 (19): 10496–10504.

Xie YC, Dong XW, Wu XM, et al. (2009) Inhibitory effects of flavonoids extracted from licorice on lipopolysaccharide‐induced acute pulmonary inflammation in mice. International Immunopharmacology 9 (2): 194–200.

Xie XH, Zang N, Li SM, et al. (2012) Resveratrol inhibits respiratory syncytial virus‐induced IL‐6 production, decreases viral replication, and down regulates TRIF expression in airway epithelial cells. Inflammation 35 (4): 1392–1401.

Xu CQ, Le JJ, Duan XH, et al. (2011) Molecular mechanism of icariin on rat asthmatic model. Chinese Medical Journal 124 (18): 2899–2906.

Yao H, Edirisinghe I, Yang SR, et al. (2008) Genetic ablation of NADPH oxidase enhances susceptibility to cigarette smoke‐induced lung inflammation and emphysema in mice. American Journal of Pathology 172 (5): 1222–1237.

Yao J, Jiang M, Zhang Y, et al. (2016) Chrysin alleviates allergic inflammation and airway remodeling in a murine model of chronic asthma. International Immunopharmacology. 32: 24–31.

Ye P, Yang XL, Chen X, et al. (2017) Hyperoside attenuates OVA‐induced allergic airway inflammation by activating Nrf2. International Immunopharmacology 44: 168–173.

Ye Y, Mo S, Feng W, et al. (2018) The ethanol extract of Involucrum castaneae ameliorated ovalbumin‐induced asthma in guinea pigs. Journal of Ethnopharmacology 230: 9–19.

Yu B, Cai W, Zhang HH, et al. (2017) Selaginella uncinata flavonoids ameliorated ovalbumin‐induced airway inflammation in a rat model of asthma. Journal of Ethnopharmacology 195: 71–80.

Zang N, Xie X, Deng Y, et al. (2011) Resveratrol‐mediated gamma interferon reduction prevents airway inflammation and airway hyperresponsiveness in respiratory syncytial virus‐infected immunocompromised mice. Journal of Virology 85 (24): 13061–13068.

Zakaryan H, Arabyan E, Oo A, et al. (2017) Flavonoids: promising natural compounds against viral infections. Archives of Virology 162 (9): 2539–2551.

Zar HJ and Levin ME (2012) Challenges in treating pediatric asthma in developing countries. Pediatric Drugs 14 (6): 353–359.

Zhang YJ, Gan RY, Li S, et al. (2015a) Antioxidant phytochemicals for the prevention and treatment of chronic diseases. Molecules 20 (12): 21138–21156.

Zhang W, Zhang X, Sheng A, et al. (2015b) Gamma‐Secretase inhibitor alleviates acute airway inflammation of allergic asthma in mice by down regulating Th17 cell differentiation. Mediators of Inflammation 2015: 258168.

Zhang B, Wang B, Cao S, et al. (2017) Silybin attenuates LPS‐induced lung injury in mice by inhibiting NF‐κB signalling and NLRP3 activation. International Journal of Molecular Medicine 39 (5): 1111–1118.

Zhou DY, Du Q, Li RR, et al. (2011) Grape seed proanthocyanidin extract attenuates airway inflammation and hyperresponsiveness in a murine model of asthma by down regulating inducible nitric oxide synthase. Planta Medica 77 (14): 1575–1581.

Zhou W and Nie X (2015) Afzelin attenuates asthma phenotypes by down regulation of GATA3 in a murine model of asthma. Molecular Medicine Reports 12 (1): 71–76.

Zhou DY, Fang SR, Zou CF, et al. (2015) Proanthocyanidin from grape seed extract inhibits airway inflammation and remodeling in a murine model of chronic asthma. Natural Product Communications 10 (2): 257–262.

Zhou DG, Diao BZ, Zhou W, et al. (2016) Oroxylin A inhibits allergic airway inflammation in ovalbumin (OVA)‐induced asthma murine model. Inflammation 39 (2): 867–872.

Zhu Q, Yang J, Han S, et al. (2011) Suppression of glycogen synthase kinase 3 activity reduces tumor growth of prostate cancer in vivo. Prostate 71 (8): 835–845.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Gandhi, Gopalsamy R, Karthik, Dhanabalan, Vasconcelos, Alan BS, de Sousa Leão, Gabriel C, Almeida, Maria LD, Sridharan, Gurunagarajan, Jothi, Gnanasekaran, Mohana, Thiruchenduran, Narain, Narendra, and Gurgel, Ricardo Q(May 2020) Flavonoids as Cytokine Immunomodulators to Reduce Airway Inflammation via Inhibition of the NF‐κB Signalling Pathway: A Systematic Overview. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0028888]