Protective effects of liquiritin apioside on cigarette smoke-induced lung epithelial cell injury
Yan Guan
Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Yuhangtang Rd-866, Hangzhou, China
Affiliated Sir Run Run Shaw Hospital of Medical College, Zhejiang University, Qingchundong Rd-3, Hangzhou, China
These authors contributed equally to this work.
Search for more papers by this authorFen-Fen Li
Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Yuhangtang Rd-866, Hangzhou, China
These authors contributed equally to this work.
Search for more papers by this authorLing Hong
Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Yuhangtang Rd-866, Hangzhou, China
Search for more papers by this authorXiao-Feng Yan
Affiliated Second Hospital of Medical College, Zhejiang University, Jiefang Rd-88, Hangzhou, China
Search for more papers by this authorGong-Li Tan
Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Yuhangtang Rd-866, Hangzhou, China
Search for more papers by this authorJun-Shan He
Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Yuhangtang Rd-866, Hangzhou, China
Search for more papers by this authorXin-Wei Dong
Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Yuhangtang Rd-866, Hangzhou, China
Search for more papers by this authorMeng-Jing Bao
Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Yuhangtang Rd-866, Hangzhou, China
Search for more papers by this authorCorresponding Author
Qiang-Min Xie
Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Yuhangtang Rd-866, Hangzhou, China
Correspondence and reprints: [email protected]Search for more papers by this authorYan Guan
Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Yuhangtang Rd-866, Hangzhou, China
Affiliated Sir Run Run Shaw Hospital of Medical College, Zhejiang University, Qingchundong Rd-3, Hangzhou, China
These authors contributed equally to this work.
Search for more papers by this authorFen-Fen Li
Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Yuhangtang Rd-866, Hangzhou, China
These authors contributed equally to this work.
Search for more papers by this authorLing Hong
Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Yuhangtang Rd-866, Hangzhou, China
Search for more papers by this authorXiao-Feng Yan
Affiliated Second Hospital of Medical College, Zhejiang University, Jiefang Rd-88, Hangzhou, China
Search for more papers by this authorGong-Li Tan
Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Yuhangtang Rd-866, Hangzhou, China
Search for more papers by this authorJun-Shan He
Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Yuhangtang Rd-866, Hangzhou, China
Search for more papers by this authorXin-Wei Dong
Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Yuhangtang Rd-866, Hangzhou, China
Search for more papers by this authorMeng-Jing Bao
Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Yuhangtang Rd-866, Hangzhou, China
Search for more papers by this authorCorresponding Author
Qiang-Min Xie
Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Yuhangtang Rd-866, Hangzhou, China
Correspondence and reprints: [email protected]Search for more papers by this authorAbstract
Cigarette smoking is associated with an increased incidence of chronic obstructive pulmonary disease (COPD). In this study, we hypothesized that liquiritin apioside (LA), a main flavonoid component from Glycyrrhiza uralensis, had antioxidant properties by inducing glutathione (GSH) biosynthesis via the inhibition of cytokines and protected lung epithelial cells against cigarette smoke-mediated oxidative stress. A549 cells were treated with cigarette smoke extract (CSE) and/or LA. ICR mice were exposed to cigarette smoke (CS) for four days with increasing exposure time for up to 6 h per day to elicit epithelial cells injury. One hour before smoke exposure, mice were treated with LA by gavage; 18 h after the last CS exposure all examinations were performed. Treatment with LA concentration-dependently prevented CSE-induced cytotoxicity, increase of TGF-β and TNF-α mRNA expression, depletion of GSH and apoptosis in A549 cells. LA at doses 3, 10 and 30 mg/kg dose-dependently inhibited pulmonary neutrophil and macrophage inflammation. Lung sections of the CS-exposed LA treated mice showed an apparently reduced pulmonary inflammation and a significant inhibitory effect on mucus containing goblet cells in the large airways. Furthermore, the CS-induced pulmonary release of TGF-β, TNF-α and myeloperoxidase activity was reduced, and superoxide dismutase activity was enhanced.These results indicate that protective roles of LA on CS-induced the lung epithelial cell injury are mediated by inhibiting TGF-β and TNF-α expression and increasing anti-oxidative levels of GSH, suggesting that LA might be effective as protective agent against epithelial injury in COPD.
References
- 1 Aoki F., Nakagawa K., Kitano M. et al. Clinical safety of licorice flavonoid oil (LFO) and pharmacokinetics of glabridin in healthy humans. J. Am. Coll. Nutr. (2007) 26 209–218.
- 2 Fiore C., Eisenhut M., Ragazzi E., Zanchin G., Armanini D. A history of the therapeutic use of liquorice in Europe. J. Ethnopharmacol. (2005) 99 317–324.
- 3 Isbrucker R.A., Burdock G.A. Risk and safety assessment on the consumption of Licorice root (Glycyrrhiza sp.), its extract and powder as a food ingredient,with emphasis on the pharmacology and toxicology of glycyrrhizin. Regul. Toxicol. Pharmacol. (2006) 46 167–192.
- 4 Olukoga A., Donaldson D. Liquorice and its health implications. J. R. Soc. Health (2000) 120 83–89.
- 5 Armanini D., Fiore C., Mattarello M.J., Bielenberg J., Palermo M. History of the endocrine effects of licorice. Exp. Clin. Endocrinol. Diabetes (2002) 110 257–261.
- 6 Xie Y.C., Dong X.W., Wu X.M., Yan X.F., Xie Q.M. Inhibitory effects of flavonoids extracted from licorice on lipopolysaccharide-induced acute pulmonary inflammation in mice, Int. Immunopharmacology (2009) 9 194–200.
- 7
Zhang Q.,
Ye M.
Chemical analysis of the Chinese herbal medicine Gan-Cao (licorice).
J. Chromatogr. A (2009) 216
1954–1969.
10.1016/j.chroma.2008.07.072 Google Scholar
- 8 Zhu Y.L., Xie Q.M., Chen J.Q., Zhang S.J. Inhibition of flavone from Glycyrrhiza uralensis on capsaicin-induced cough reflex in guinea pig. Chin. Trad. Herbal Drugs (2006) 37 1048–1051.
- 9 Kamei J., Saitoh A., Asano T. et al. Pharmacokinetic and pharmacodynamic profiles of the antitussive principles of Glycyrrhizae radix (licorice), a main component of the Kampo preparation Bakumondo-to (Mai-men-dong-tang). Eur. J. Pharmacol. (2005) 507 163–168.
- 10 Rathee P., Chaudhary H., Rathee S., Rathee D., Kumar V., Kohli K. Mechanism of action of flavonoids as anti-inflammatory agents: a review. Inflamm. Allergy Drug Targets (2009) 8 229–235.
- 11 Rice-Evans C. Flavonoid antioxidants. Curr. Med. Chem. (2001) 8 797–807.
- 12 Terao J. Dietary flavonoids as antioxidants. Forum Nutr. (2009) 61 87–94.
- 13 Furusawa J., Funakoshi-Tago M., Tago K. et al. Licochalcone A significantly suppresses LPS signaling pathway through the inhibition of NF-κB p65 phosphorylation at serine 276. Cell. Signal. (2009) 21 778–785.
- 14 Shin E.M., Zhou H.Y., Guo L.Y. et al. Anti-inflammatory effects of glycyrol isolated from Glycyrrhiza uralensis in LPS-stimulated RAW264.7 macrophages. Int. Immunopharmacol. (2008) 8 1524–1532.
- 15 Nakanishi T., Inada A., Kobayashi K., Yoneda K. Flavonoid glycosides of the roots of Glycyrrhiza uralensis. Phytochemistry (1985) 24 339–341.
- 16 Aida K., Tawata H., Shindo H. et al. The existence of aldose reductase inhibitors in some Kampo medicines (oriental herb prescriptions). Planta Med. (1989) 55 22–26.
- 17 Kobayashi S., Miyamoto T., Kimura I., Kimura M. Inhibitory effect of isoliquiritin, a compound in Licorice Root, on angiogenesis in vivo and tube formation in vitro. Biol. Pharm. Bull. (1995) 18 1382–1386.
- 18 Su Y., Han W., Giraldo C., De Li Y., Block E.R. Effect of cigarette smoke extract on nitric oxide synthase in pulmonary artery endothelial cells. Am. J. Respir. Cell Mol. Biol. (1998) 19 819–825.
- 19 Rahman I., Kode A., Biswas S.K. Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling method. Nat. Protoc. (2006) 1 3159–3165.
- 20 Lannan S., Donaldson K., Brown D., MacNee W. Effect of cigarette smoke and its condensates on alveolar epithelial cell injury in vitro. Am. J. Physiol. Lung Cell. Mol. Physiol. (1994) 266 L92–L100.
- 21 Reynolds P.R., Cosio M.G., Hoidal J.R. Cigarette smoke-induced Egr-1 upregulates proinflammatory cytokines in pulmonary epithelial cells. Am. J. Respir. Cell Mol. Biol. (2006) 35 314–319.
- 22 Wang R.D., Wright J.L., Churg A. Transforming growth factor-β1 drives airway remodeling in cigarette smoke-exposed tracheal explants. Am. J. Respir. Cell Mol. Biol. (2005) 33 387–393.
- 23 Tagawa Y., Hiramatsu N., Kasai A. et al. Induction of apoptosis by cigarette smoke via ROS-dependent endoplasmic reticulum stress and CCAAT/enhancer-binding protein-homologous protein (CHOP). Free Radic. Biol. Med. (2008) 45 50–59.
- 24 Pouli A.E., Hatzinikolaou D.G., Piperi C., Stavridou A., Psallidopoulos M.C., Stavrides J.C. The cytotoxic effect of volatile organic compounds of the gas phase of cigarette smoke on lung epithelial cells. Free Radic. Biol. Med. (2003) 34 345–355.
- 25 Rahman I., MacNee W. Oxidative stress and regulation of glutathione in lung inflammation. Eur. Respir. J. (2000) 16 534–554.
- 26 Araya J., Cambier S., Markovics J.A. et al. Squamous metaplasia amplifies pathologic epithelial-mesenchymal interactions in COPD patients. J. Clin. Invest. (2007) 117 3551–3562.
- 27 Sapey E., Wood A.M., Ahmad A., Stockley R.A. Tumor necrosis factor-α rs361525 polymorphism is associated with increased local production and downstream inflammation in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. (2010) 182 192–199.
- 28 Rahman I., Biswas S.K., Kode A. Oxidant and antioxidant balance in the airways and airway diseases. Eur. J. Pharmacol. (2006) 533 222–239.
- 29 Arsalane K., Dubois C.M., Muanza T. et al. Transforming growth factor-beta1 is a potent inhibitor of glutathione synthesis in the lung epithelial cell line A549: transcriptional effect on the GSH rate-limiting enzyme gamma-glutamylcysteine synthetase. Am. J. Respir. Cell Mol. Biol. (1997) 17 599–607.
- 30 Rahman I., Li X.Y., Donaldson K., Harrison D.J., MacNee W. Glutathione homeostasis in alveolar epithelial cells in vitro and lung in vivo under oxidative stress. Am. J. Physiol. Lung Cell. Mol. Physiol. (1995) 269 L285–L292.
- 31 Hecker L., Vittal R., Jones T. et al. NADPH oxidase-4 mediates myofibroblast activation and fibrogenic responses to lung injury. Nat. Med. (2009) 15 1077–1081.
- 32 Bellocq A., Azoulay E., Marullo S. et al. Reactive oxygen and nitrogen intermediates increase transforming growth factor-β1 release from human epithelial alveolar cells through two different mechanisms. Am. J. Respir. Cell Mol. Biol. (1999) 21 128–136.
- 33 Vignola A.M., Chanez P., Chiappara G. et al. Release of transforming growth factor-beta (TGF-beta) and fibronectin by alveolar macrophages in airway diseases. Clin. Exp. Immunol. (1996) 106 114–119.
- 34 Vignola A.M., Chanez P., Chiappara G. et al. Transforming growth factor-beta expression in mucosal biopsies in asthma and chronic bronchitis. Am. J. Respir. Crit. Care Med. (1997) 156 591–599.
- 35 Churg A., Wang R.D., Tai H., Wang X., Xie C., Wright J.L. Tumor necrosis factor-alpha drives 70% of cigarette smoke-induced emphysema in the mouse. Am. J. Respir. Crit. Care Med. (2004) 170 492–298.
- 36 Rahman I., Gilmour P.S., Jimenez L.A., MacNee W. Oxidative stress and TNF-alpha induce histone acetylation and NF-kappaB/AP-1 activation in alveolar epithelial cells: potential mechanism in gene transcription in lung inflammation. Mol. Cell. Biochem. (2002) 234–235 239–248.
- 37 Mackay F., Loetscher H., Stueber D., Gehr G., Lesslauer W. Tumor necrosis factor alpha (TNF-alpha)-induced cell adhesion to human endothelial cells is under dominant control of one TNF receptor type, TNF-R55. J. Exp. Med (1993) 177 1277–1286.
- 38 Di F.M., Barbier D., Mege J.L., Orehek J. Tumor necrosis factor-alpha levels and weight loss in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. (1994) 150 1453–1455.
- 39 Duong C., Seow H.J., Bozinovski S., Crack P.J., Anderson G.P., Vlahos R. Glutathione peroxidase-1 protects against cigarette smoke-induced lung inflammation in mice. Am. J. Physiol. Lung Cell. Mol. Physiol. (2010) 299 L425–L433.
- 40 Valença S.S., Pimenta W.A., Rueff-Barroso C.R. et al. Involvement of nitric oxide in acute lung inflammation induced by cigarette smoke in the mouse. Nitric Oxide (2009) 20 175–181.
- 41 Chin Y.W., Jung H.A., Liu Y. et al. Anti-oxidant constituents of the roots and stolons of licorice (Glycyrrhiza glabra). J. Agric. Food. Chem. (2007) 55 4691–4697.
- 42
Homma M.,
Oka K.,
Taniguchi C.,
Niitsuma T.,
Hayashi T.
Systematic analysis of post-administrative Saiboku-to urine by liquid chromatography to determine pharmacokinetics of traditional Chinese medicine.
Biomed. Chromatogr. (1997) 11
125–131.
10.1002/(SICI)1099-0801(199705)11:3<125::AID-BMC631>3.0.CO;2-L CAS PubMed Web of Science® Google Scholar
- 43 Homma M., Oka K., Yamada T., Niitsuma T., Ihto H., Takahashi N. A strategy for discovering biologically active compounds with high probability in traditional Chinese herb remedies: an application of Saiboku-to in bronchial asthma. Anal. Biochem. (1992) 202 179–187.
- 44 Tamaki T., Niitsuma T. The clinical effect of Bakumondo-to and the analysis of its urinary extracta: antitussive action of Bakmondo-to in bronchial asthma and its active components. J. Tokyo Med. Univ. (1999) 57 23–30.
- 45 Asano T., Ishihara K., Morota T., Takeda S., Aburada M. Permeability of the flavonoids liquiritigenin and its glycosides in licorice roots and davidigenin, a hydrogenated metabolite of liquiritigenin, using human intestinal cell line Caco-2. J. Ethnopharmacol. (2003) 89 285–289.
- 46 Dai J.Y., Yang J.L., Li C. Transport and metabolism of flavonoids from Chinese herbal remedy Xiaochaihu- tang across human intestinal Caco-2 cell monolayers. Acta Pharmacol. Sin. (2008) 29 1086–1093.
- 47 Yee S.. In vitro permeability across Caco-2 cell (colonic) can predict in vivo (small intestinal) absorption in man-fact or myth. Pharm. Res. (1997) 14, 763–766.
- 48 Li L., Liang S., Du F., Li C. Simultaneous quantification of multiple licorice flavonoids in rat plasma. J. Am. Soc. Mass Spectrom. (2007) 18 778–782.
Citing Literature
