title: Intranasal curcumin ameliorates airway inflammation and obstruction by regulating MAPKinase activation (p38, Erk and JNK) and prostaglandin D2 release in murine model of asthma.
abstract: Asthma, a multifactorial, chronic inflammatory disease encompasses multiple complex pathways releasing number of mediators by activated mast cells, eosinophils and T lymphocytes, leading to its severity. Presently available medications are associated with certain limitations, and hence, it is imperative to search for anti-inflammatory drug preferably targeting signaling cascades involved in inflammation thereby suppressing inflammatory mediators without any side effect. Curcumin, an anti-inflammatory molecule with potent anti-asthmatic potential has been found to suppress asthmatic features by inhibiting airway inflammation and bronchoconstriction if administered through nasal route. The present study provides new insight towards anti-asthmatic potential of intranasal curcumin at lower doses (2.5 and 5.0 mg/kg) in Balb/c mice sensitized and challenged with ovalbumin (OVA) which is effective in inhibiting airway inflammation. These investigations suggest that intranasal curcumin (2.5 and 5.0 mg/kg) regulates airway inflammation and airway obstruction mainly by modulating cytokine levels (IL-4, 5, IFN-ƴ and TNF-α) and sPLA2 activity thereby inhibiting PGD2 release and COX-2 expression. Further, the suppression of p38 MAPK, ERK 42/44 and JNK54/56 activation elucidate the mechanism behind the inhibitory role of intranasal curcumin in asthma progression. Thus, curcumin could be better alternative for the development of nasal formulations and inhalers in near future.
authors.affiliation: Department of Zoology, MMV, Banaras Hindu University, Varanasi 221005, India.
authors.lastname: Subhashini
authors.affiliation: Department of Zoology, MMV, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Preeti S
authors.initials: PS
authors.lastname: Chauhan
authors.affiliation: Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University.
authors.forename: D
authors.initials: D
authors.lastname: Dash
authors.affiliation: Department of Immunobiology, Indian Institute of Toxicology and Research, Lucknow 226001, India.
authors.forename: B N
authors.initials: BN
authors.lastname: Paul
authors.affiliation: Department of Zoology, MMV, Banaras Hindu University, Varanasi 221005, India. Electronic address: rashmirs98@rediffmail.com.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Singh
mesh_terms: D000281:Administration, Intranasal; D000402:Airway Obstruction / Q000188:drug therapy*; D000818:Animals; D001249:Asthma / Q000188:drug therapy*; D003474:Curcumin / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015230:Prostaglandin D2 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D003474:Curcumin; D015230:Prostaglandin D2
keywords: Eosinophils; Extracellular regulated kinases and c-Jun N-terminal kinases; MAPK; Prostaglandin D2