title: Tinospora cordifolia extract modulates COX-2, iNOS, ICAM-1, pro-inflammatory cytokines and redox status in murine model of asthma.
abstract: BACKGROUND
  Tinospora cordifolia (Willd.) Miers is an important constituent of several ayurvedic medicinal preparations. In Ayurveda it is mentioned as "rasayan" and traditionally used for the treatment of asthma, chronic cough besides other ailments. This study was carried out to study the mechanisms involved in protection accorded by extract of Tinospora cordifolia (Tc) stem to asthmatic mice by regulation of oxidative stress, pro-inflammatory mediator release and redox signaling involving NFκB.
  
  
  METHODS
  BALB/c mice were sensitized with intraperitoneal (i.p.) Ovalbumin (Ova) on days 0 and 14, followed by intranasal Ovalbumin (Ova) challenge on days 24 and 27 to generate an in vivo asthma model. Tc extract (hydroalcoholic, 100 mg/kg) and dexamethasone (1 mg/kg) were given orally from day 15 to 23 to the Tc+Ova treated group and Dex+Ova treated group respectively. Oxidative stress parameters e.g. activity of superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx) and catalase, lipid peroxidation, GSH/GSSG ratio, protein carbonyl content, eosinophil peroxidase, myeloperoxidase activity, and NO release were measured in tissue, blood and bronchoalveolar lavage fluid (BALF). Estimation of cytokines was done in BALF. Western blot analysis was done for IκB α, iNOS, COX-2, iCAM-1 and pJNK MAPKs along with histopathology.
  
  
  RESULTS
  Tc extract treated mice showed decreased airway hyper-responsiveness, eosinophil count and IgE content in blood as compared to Ova treated asthmatic mice. Increase in activities of SOD, catalase, glutathione reductase, glutathione peroxidase as well as GSH/GSSG ratio was observed while a decrease in MDA formation, protein carbonyl content, eosinophil peroxidase, myeloperoxidase activity and NO release in BALF was seen in Tc treated mice. In BALF, levels of cytokines IL-4 and TNF-α were reduced and IFN-γ levels increased in extract treated mice. At the same time Tc treatment of Ova-challenged mice significantly increased the level of IκB α, cytosolic inhibitor of redox sensitive transcription factor NFκB. Immunoblot analysis revealed considerable decrease in the levels of COX-2, ICAM-1, iNOS, and pJNK. Histopathology and PAS staining also indicate a protective effect of Tc extract in inflammation and mucus hyper-secretion due to goblet cell hyperplasia.
  
  
  CONCLUSIONS
  The results suggest a protective effect of Tc extract against oxidative stress, pro-inflammatory mediator release and redox signaling in the murine model of asthma. The Tc extract shows therapeutic potential for management of asthmatic inflammation and other lung inflammatory conditions.
authors.affiliation: Herbal Research Section, Food Drug & Chemical Toxicology Division, CSIR - Indian Institute of Toxicology Research, P.O. Box 80, M.G. Marg, Lucknow 226001, Uttar Pradesh, India. Electronic address: meetmt@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Tiwari
authors.affiliation: Department of Biochemistry, University of Lucknow, Lucknow 226007, Uttar Pradesh, India. Electronic address: upendradwivedi@hotmail.com.
authors.forename: U N
authors.initials: UN
authors.lastname: Dwivedi
authors.affiliation: Herbal Research Section, Food Drug & Chemical Toxicology Division, CSIR - Indian Institute of Toxicology Research, P.O. Box 80, M.G. Marg, Lucknow 226001, Uttar Pradesh, India. Electronic address: poonam_kakkar@yahoo.com.
authors.forename: P
authors.initials: P
authors.lastname: Kakkar
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010047:Ovalbumin / Q000633:toxicity; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D018547:Plant Stems; D031610:Tinospora
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D010936:Plant Extracts; D018799:Intercellular Adhesion Molecule-1; D010047:Ovalbumin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2
keywords: Asthma; COX-2; IκB; Oxidative stress; Redox signaling; TNF-α; pJNK