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      Antioxidant components of naturally-occurring oils exhibit marked anti-inflammatory activity in epithelial cells of the human upper respiratory system

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          Abstract

          Background

          The upper respiratory tract functions to protect lower respiratory structures from chemical and biological agents in inspired air. Cellular oxidative stress leading to acute and chronic inflammation contributes to the resultant pathology in many of these exposures and is typical of allergic disease, chronic sinusitis, pollutant exposure, and bacterial and viral infections. Little is known about the effective means by which topical treatment of the nose can strengthen its antioxidant and anti-inflammatory defenses. The present study was undertaken to determine if naturally-occurring plant oils with reported antioxidant activity can provide mechanisms through which upper respiratory protection might occur.

          Methods

          Controlled exposure of the upper respiratory system to ozone and nasal biopsy were carried out in healthy human subjects to assess mitigation of the ozone-induced inflammatory response and to assess gene expression in the nasal mucosa induced by a mixture of five naturally-occurring antioxidant oils - aloe, coconut, orange, peppermint and vitamin E. Cells of the BEAS-2B and NCI-H23 epithelial cell lines were used to investigate the source and potential intracellular mechanisms of action responsible for oil-induced anti-inflammatory activity.

          Results

          Aerosolized pretreatment with the mixed oil preparation significantly attenuated ozone-induced nasal inflammation. Although most oil components may reduce oxidant stress by undergoing reduction, orange oil was demonstrated to have the ability to induce long-lasting gene expression of several antioxidant enzymes linked to Nrf2, including HO-1, NQO1, GCLm and GCLc, and to mitigate the pro-inflammatory signaling of endotoxin in cell culture systems. Nrf2 activation was demonstrated. Treatment with the aerosolized oil preparation increased baseline levels of nasal mucosal HO-1 expression in 9 of 12 subjects.

          Conclusions

          These data indicate that selected oil-based antioxidant preparations can effectively reduce inflammation associated with oxidant stress-related challenge to the nasal mucosa. The potential for some oils to activate intracellular antioxidant pathways may provide a powerful mechanism through which effective and persistent cytoprotection against airborne environmental exposures can be provided in the upper respiratory mucosa.

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          Most cited references55

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          Oxidative stress and redox regulation of lung inflammation in COPD.

          Reactive oxygen species, either directly or via the formation of lipid peroxidation products, may play a role in enhancing inflammation through the activation of stress kinases (c-Jun activated kinase, extracellular signal-regulated kinase, p38) and redox-sensitive transcription factors, such as nuclear factor (NF)-kappaB and activator protein-1. This results in increased expression of a battery of distinct pro-inflammatory mediators. Oxidative stress activates NF-kappaB-mediated transcription of pro-inflammatory mediators either through activation of its activating inhibitor of kappaB-alpha kinase or the enhanced recruitment and activation of transcriptional co-activators. Enhanced NF-kappaB-co-activator complex formation results in targeted increases in histone modifications, such as acetylation leading to inflammatory gene expression. Emerging evidence suggests the glutathione redox couple may entail dynamic regulation of protein function by reversible disulphide bond formation on kinases, phosphatases and transcription factors. Oxidative stress also inhibits histone deacetylase activity and in doing so further enhances inflammatory gene expression and may attenuate glucocorticoid sensitivity. The antioxidant/anti-inflammatory effects of thiol molecules (glutathione, N-acetyl-L-cysteine and N-acystelyn, erdosteine), dietary polyphenols (curcumin-diferuloylmethane, cathechins/quercetin and reserveratol), specific spin traps, such as alpha-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (extracellular superoxide dismutase (SOD) mimetic, SOD mimetic M40419 and SOD, and catalase manganic salen compound, eukarion-8), porphyrins (AEOL 10150 and AEOL 10113) and theophylline have all been shown to play a role in either controlling NF-kappaB activation or affecting histone modifications with subsequent effects on inflammatory gene expression in lung epithelial cells. Thus, oxidative stress regulates both key signal transduction pathways and histone modifications involved in lung inflammation. Various approaches to enhance lung antioxidant capacity and clinical trials of antioxidant compounds in chronic obstructive pulmonary disease are also discussed.
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            Oxidant and antioxidant balance in the airways and airway diseases.

            Although oxygen is a prerequisite to life, at concentrations beyond the physiological limits it may be hazardous to the cells. Since the lungs are directly exposed to very high amounts of oxygen, it is imperative for the organ to possess defences against possible oxidative challenge. The lungs are therefore endowed with an armamentarium of a battery of endogenous agents called antioxidants. The antioxidant species help the lungs ward off the deleterious consequences of a wide variety of oxidants/reactive oxygen species such as superoxide anion, hydroxyl radical, hypohalite radical, hydrogen peroxide and reactive nitrogen species such as nitric oxide, peroxynitrite, nitrite produced endogenously and sometimes accessed through exposure to the environment. The major non-enzymatic antioxidants of the lungs are glutathione, vitamins C and E, beta-carotene, uric acid and the enzymatic antioxidants are superoxide dismutases, catalase and peroxidases. These antioxidants are the first lines of defence against the oxidants and usually act at a gross level. Recent insights into cellular redox chemistry have revealed the presence of certain specialized proteins such as peroxiredoxins, thioredoxins, glutaredoxins, heme oxygenases and reductases, which are involved in cellular adaptation and protection against an oxidative assault. These molecules usually exert their action at a more subtle level of cellular signaling processes. Aberrations in oxidant: antioxidant balance can lead to a variety of airway diseases, such as asthma, chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis which is the topic of discussion in this review.
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              A review of the bioactivity and potential health benefits of peppermint tea (Mentha piperita L.).

              Peppermint (Mentha piperita L.) is one of the most widely consumed single ingredient herbal teas, or tisanes. Peppermint tea, brewed from the plant leaves, and the essential oil of peppermint are used in traditional medicines. Evidence-based research regarding the bioactivity of this herb is reviewed. The phenolic constituents of the leaves include rosmarinic acid and several flavonoids, primarily eriocitrin, luteolin and hesperidin. The main volatile components of the essential oil are menthol and menthone. In vitro, peppermint has significant antimicrobial and antiviral activities, strong antioxidant and antitumor actions, and some antiallergenic potential. Animal model studies demonstrate a relaxation effect on gastrointestinal (GI) tissue, analgesic and anesthetic effects in the central and peripheral nervous system, immunomodulating actions and chemopreventive potential. Human studies on the GI, respiratory tract and analgesic effects of peppermint oil and its constituents have been reported. Several clinical trials examining the effects of peppermint oil on irritable bowel syndrome (IBS) symptoms have been conducted. However, human studies of peppermint leaf are limited and clinical trials of peppermint tea are absent. Adverse reactions to peppermint tea have not been reported, although caution has been urged for peppermint oil therapy in patients with GI reflux, hiatal hernia or kidney stones.
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                Author and article information

                Journal
                Respir Res
                Respiratory Research
                BioMed Central
                1465-9921
                1465-993X
                2011
                13 July 2011
                : 12
                : 1
                : 92
                Affiliations
                [1 ]Health Effects Assessment Laboratory, Department of Environmental Health Sciences, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
                Article
                1465-9921-12-92
                10.1186/1465-9921-12-92
                3154159
                21752292
                264ee7c4-e3c1-4d1c-9b36-cc62d3d9e9bb
                Copyright ©2011 Gao et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 January 2011
                : 13 July 2011
                Categories
                Research

                Respiratory medicine
                Respiratory medicine

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