The effects of Gamijinhae-tang on elastase/lipopolysaccharide-induced lung inflammation in an animal model of acute lung injury

BMC Complementary and Alternative Medicine

Hyunsu Bae³  Sungki Jung²  Heejae Jung²  Seung-Hun Cho¹  Young Pyo Jang⁶  Youngeun Kim⁴  HaRyeon Jang²  Sung-Hwa Sohn⁵ 

[1] Department of Neuropsychiatry, College of Oriental Medicine, Kyung Hee University, #1, Hoegi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea;Division of Allergy and Respiratory System, Department of Oriental Internal Medicine, College of Oriental Medicine, Kyung Hee University, #1, Hoegi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea;Institute of Oriental Medicine, Kyung Hee University, Seoul, 130-701, South Korea;Department of Physiology, College of Oriental Medicine, Kyung Hee University, #1, Hoegi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea;Present Address: National Academy of Agricultural Science, Rural Development Administration, Suwon, 441-707, South Korea;Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, #1, Hoegi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea

关键词: Goblet cell;    IL-1β;    IL-6;    Elastase;    Gamijinhae-tang;    COPD;    ALI;   

Others  :  1221070
DOI  :  10.1186/1472-6882-13-176

 received in 2012-09-10, accepted in 2013-07-15,  发布年份 2013

【 摘 要 】

Background

Gamijinhae-tang (GJHT) has long been used in Korea to treat respiratory diseases. The therapeutic effect of GJHT is likely associated with its anti-inflammatory activity. However, the precise mechanisms underlying its effects are unknown. This study was conducted to evaluate the protective effects of GJHT in a porcine pancreatic elastase (PPE) and lipopolysaccharide(LPS) induced animal model of acute lung injury (ALI).

Methods

In this study, mice were intranasally exposed to PPE and LPS for 4 weeks to induce chronic obstructive pulmonary disease (COPD)-like lung inflammation. Two hours prior to PPE and LPS administration, the treatment group was administered GJHT extracts via an oral injection. The numbers of neutrophils, lymphocytes, macrophages and total cells in the bronchoalveolar lavage (BAL) fluid were counted, and pro-inflammatory cytokines were also measured. For histologic analysis, hematoxylin and eosin (H&E) stains and periodic acid-Schiff (PAS) stains were evaluated.

Results

After inducing ALI by treating mice with PPE and LPS for 4 weeks, the numbers of neutrophils, lymphocytes and total cells were significantly lower in the GJHT group than in the ALI group. In addition, the IL-1β and IL-6 levels were significantly decreased in the GJHT group. The histological results also demonstrated the attenuation effect of GJHT on PPE- and LPS-induced lung inflammation.

Conclusions

The results of this study indicate that GJHT has significantly reduces PPE- and LPS-induced lung inflammation. The remarkable protective effects of GJHT suggest its therapeutic potential in COPD treatment.

【 授权许可】

   
2013 Sohn et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】

• [1]Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, Fukuchi Y, Jenkins C, Rodriguez-Roisin R, van Weel C, et al.: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2007, 176(6):532-555.
• [2]Cho MH, Castaldi PJ, Wan ES, Siedlinski M, Hersh CP, Demeo DL, Himes BE, Sylvia JS, Klanderman BJ, Ziniti JP, et al.: A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13. Hum Mol Genet 2012, 21(4):947-957.
• [3]Pauwels RA, Buist AS, Ma P, Jenkins CR, Hurd SS: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: National Heart, Lung, and Blood Institute and World Health Organization Global Initiative for Chronic Obstructive Lung Disease (GOLD): executive summary. Respir Care 2001, 46(8):798-825.
• [4]Barnes PJ: Chronic obstructive pulmonary disease. N Engl J Med 2000, 343(4):269-280.
• [5]Konigshoff M, Kneidinger N, Eickelberg O: TGF-beta signaling in COPD: deciphering genetic and cellular susceptibilities for future therapeutic regimen. Swiss Med Wkly 2009, 139(39–40):554-563.
• [6]Groneberg DA, Chung KF: Models of chronic obstructive pulmonary disease. Respir Res 2004, 5:18. BioMed Central Full Text
• [7]Ferrer E, Peinado VI, Diez M, Carrasco JL, Musri MM, Martinez A, Rodriguez-Roisin R, Barbera JA: Effects of cigarette smoke on endothelial function of pulmonary arteries in the guinea pig. Respir Res 2009, 10:76. BioMed Central Full Text
• [8]Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, Cherniack RM, Rogers RM, Sciurba FC, Coxson HO, et al.: The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 2004, 350(26):2645-2653.
• [9]Barnes PJ: The cytokine network in asthma and chronic obstructive pulmonary disease. J Clin Invest 2008, 118(11):3546-3556.
• [10]Barnes PJ: Mediators of chronic obstructive pulmonary disease. Pharmacol Rev 2004, 56(4):515-548.
• [11]Hasday JD, Bascom R, Costa JJ, Fitzgerald T, Dubin W: Bacterial endotoxin is an active component of cigarette smoke. Chest 1999, 115(3):829-835.
• [12]Sebastian A, Pehrson C, Larsson L: Elevated concentrations of endotoxin in indoor air due to cigarette smoking. J Environ Monit 2006, 8(5):519-522.
• [13]Brass DM, Hollingsworth JW, Cinque M, Li Z, Potts E, Toloza E, Foster WM, Schwartz DA: Chronic LPS inhalation causes emphysema-like changes in mouse lung that are associated with apoptosis. Am J Respir Cell Mol Biol 2008, 39(5):584-590.
• [14]Sajjan U, Ganesan S, Comstock AT, Shim J, Wang Q, Nagarkar DR, Zhao Y, Goldsmith AM, Sonstein J, Linn MJ, et al.: Elastase- and LPS-exposed mice display altered responses to rhinovirus infection. Am J Physiol Lung Cell Mol Physiol 2009, 297(5):L931-L944.
• [15]Kim Y, Joo Y, Jung HJ, Seo U: Effects of Gamijinhae-tang (Jiaweizhenke-tang) on Tracheal Smooth Muscle Contraction and Mucin Secretion from Airway Epithelial Cells. J Korean Oriental Med 2008, 29(3):63-75.
• [16]Byun J, Park YB, Yang S, An J, Park S: Effects of Gamijinhae-tang and Socheongryong-tang-ga-seokgo on PMA- induced Production of Airway Mucin and Expression of Airway MUC5AC Gene. J Korean Oriental Inten Med 2008, 29(3):765-777.
• [17]Chung HS, Kang M, Cho C, Parvez S, Park CH, Kim D, Oh J, Kim H, Shin M, Hong M, et al.: Inhibition of nitric oxide and tumor necrosis factor-alpha by moutan cortex in activated mouse peritoneal macrophages. Biol Pharm Bull 2007, 30(5):912-916.
• [18]Sohn SH, Ko E, Oh BG, Kim J, Choi E, Kim SH, Kim Y, Shin M, Hong M, Bae H: Global gene analysis of Erigeron canadensis-treated TNF-alpha-, IL-4- and IL-1beta-stimulated A549 human epithelial cells. Ann Nutr Metab 2009, 54(3):227-235.
• [19]Sohn SH, Ko E, Kim Y, Shin M, Hong M, Bae H: Genomewide expression profile of forsythia suspensa on lipopolysaccaride-induced activation in microglial cells. Mol Cell Toxicol 2008, 4(2):113-123.
• [20]Sohn SH, Ko E, Oh BG, Kim SH, Kim Y, Shin M, Hong M, Bae H: Inhibition effects of Vitex rotundifolia on inflammatory gene expression in A549 human epithelial cells. Ann Allergy Asthma Immunol 2009, 103(2):152-159.
• [21]Tamimi A, Serdarevic D, Hanania NA: The effects of cigarette smoke on airway inflammation in asthma and COPD: therapeutic implications. Respir Med 2012, 106(3):319-328.
• [22]Barnes PJ: Immunology of asthma and chronic obstructive pulmonary disease. Nat Rev Immunol 2008, 8(3):183-192.
• [23]Masoli M, Fabian D, Holt S, Beasley R: The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy 2004, 59(5):469-478.
• [24]Bousquet J, Clark TJ, Hurd S, Khaltaev N, Lenfant C, O’Byrne P, Sheffer A: GINA guidelines on asthma and beyond. Allergy 2007, 62(2):102-112.
• [25]Burge PS, Lewis SA: So inhaled steroids slow the rate of decline of FEV1 in patients with COPD after all? Thorax 2003, 58(11):911-913.
• [26]Calverley PM, Boonsawat W, Cseke Z, Zhong N, Peterson S, Olsson H: Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease. Eur Respir J 2003, 22(6):912-919.
• [27]Busse WW, Lemanske RF Jr: Asthma. N Engl J Med 2001, 344(5):350-362.
• [28]Longui CA: Glucocorticoid therapy: minimizing side effects. J Pediatr (Rio J) 2007, 83(5 Suppl):S163-S177.
• [29]Lemanske RF Jr, Allen DB: Choosing a long-term controller medication in childhood asthma. The proverbial two-edged sword. Am J Respir Crit Care Med 1997, 156(3 Pt 1):685-687.
• [30]Page CP, Spina D: Phosphodiesterase inhibitors in the treatment of inflammatory diseases. Handb Exp Pharmacol 2011, 204:391-414.
• [31]Hawkins NM, Wang D, Petrie MC, Pfeffer MA, Swedberg K, Granger CB, Yusuf S, Solomon SD, Ostergren J, Michelson EL, et al.: Baseline characteristics and outcomes of patients with heart failure receiving bronchodilators in the CHARM programme. Eur J Heart Fail 2010, 12(6):557-565.
• [32]Hawkins NM, Jhund PS, Simpson CR, Petrie MC, Macdonald MR, Dunn FG, Macintyre K, McMurray JJ: Primary care burden and treatment of patients with heart failure and chronic obstructive pulmonary disease in Scotland. Eur J Heart Fail 2010, 12(1):17-24.
• [33]Carpenter DO, Briggs DB, Knox AP, Strominger N: Excitation of area postrema neurons by transmitters, peptides, and cyclic nucleotides. J Neurophysiol 1988, 59(2):358-369.
• [34]Blanc PD, Trupin L, Earnest G, Katz PP, Yelin EH, Eisner MD: Alternative therapies among adults with a reported diagnosis of asthma or rhinosinusitis : data from a population-based survey. Chest 2001, 120(5):1461-1467.
• [35]Clark CE, Arnold E, Lasserson TJ, Wu T: Herbal interventions for chronic asthma in adults and children: a systematic review and meta-analysis. Prim Care Respir J 2010, 19(4):307-314.
• [36]Turner J, Jones CE: Regulation of mucin expression in respiratory diseases. Biochem Soc Trans 2009, 37(Pt 4):877-881.
• [37]Rogers DF: Airway mucus hypersecretion in asthma: an undervalued pathology? Curr Opin Pharmacol 2004, 4(3):241-250.
• [38]Rose MC, Voynow JA: Respiratory tract mucin genes and mucin glycoproteins in health and disease. Physiol Rev 2006, 86(1):245-278.
• [39]Kubo M, Asano T, Shiomoto H, Matsuda H: Studies on rehmanniae radix. I. Effect of 50% ethanolic extract from steamed and dried rehmanniae radix on hemorheology in arthritic and thrombosic rats. Biol Pharm Bull 1994, 17(9):1282-1286.
• [40]Kiho T, Watanabe T, Nagai K, Ukai S: Hypoglycemic activity of polysaccharide fraction from rhizome of Rehmannia glutinosa Libosch. f. hueichingensis Hsiao and the effect on carbohydrate metabolism in normal mouse liver. Yakugaku Zasshi 1992, 112(6):393-400.
• [41]Baek GH, Jang YS, Jeong SI, Cha J, Joo M, Shin SW, Ha KT, Jeong HS: Rehmannia glutinosa suppresses inflammatory responses elicited by advanced glycation End products. Inflamm 2012, 35(4):1232-1241.
• [42]Kang DG, Sohn EJ, Moon MK, Lee YM, Lee HS: Rehmannia glutinose ameliorates renal function in the ischemia/reperfusion-induced acute renal failure rats. Biol Pharm Bull 2005, 28(9):1662-1667.
• [43]Yokozawa T, Kim HY, Yamabe N: Amelioration of diabetic nephropathy by dried Rehmanniae Radix (Di Huang) extract. Am J Chin Med 2004, 32(6):829-839.
• [44]Kim HM, An CS, Jung KY, Choo YK, Park JK, Nam SY: Rehmannia glutinosa inhibits tumour necrosis factor-alpha and interleukin-1 secretion from mouse astrocytes. Pharmacol Res 1999, 40(2):171-176.
• [45]Dong H, He L, Huang M, Dong Y: Anti-inflammatory components isolated from Atractylodes macrocephala Koidz. Nat Prod Res 2008, 22(16):1418-1427.
• [46]Li CQ, He LC, Dong HY, Jin JQ: Screening for the anti-inflammatory activity of fractions and compounds from Atractylodes macrocephala koidz. J Ethnopharmacol 2007, 114(2):212-217.
• [47]Shan JJ, Tian GY: [Studies on physico-chemical properties and hypoglycemic activity of complex polysaccharide AMP-B from Atractylodes macrocephala Koidz]. Yao Xue Xue Bao 2003, 38(6):438-441.
• [48]Yang T, Jia M, Zhou S, Pan F, Mei Q: Antivirus and immune enhancement activities of sulfated polysaccharide from Angelica sinensis. Int J Biol Macromol 2012, 50(3):768-772.
• [49]Lee YC, Lee JC, Seo YB, Kook YB: Liriopis tuber inhibit OVA-induced airway inflammation and bronchial hyperresponsiveness in murine model of asthma. J Ethnopharmacol 2005, 101(1–3):144-152.
• [50]Choi SB, Wha JD, Park S: The insulin sensitizing effect of homoisoflavone-enriched fraction in Liriope platyphylla Wang et Tang via PI3-kinase pathway. Life Sci 2004, 75(22):2653-2664.
• [51]Jeong S, Chae K, Jung YS, Rho YH, Lee J, Ha J, Yoon KH, Kim GC, Oh KS, Shin SS, et al.: The Korean traditional medicine Gyeongshingangjeehwan inhibits obesity through the regulation of leptin and PPARalpha action in OLETF rats. J Ethnopharmacol 2008, 119(2):245-251.
• [52]Kim SW, Chang IM, Oh KB: Inhibition of the bacterial surface protein anchoring transpeptidase sortase by medicinal plants. Biosci Biotechnol Biochem 2002, 66(12):2751-2754.
• [53]Hur J, Lee P, Kim J, Kim AJ, Kim H, Kim SY: Induction of nerve growth factor by butanol fraction of Liriope platyphylla in C6 and primary astrocyte cells. Biol Pharm Bull 2004, 27(8):1257-1260.
• [54]Li HB, Jiang Y, Chen F: Separation methods used for Scutellaria baicalensis active components. J Chromatogr B Analyt Technol Biomed Life Sci 2004, 812(1–2):277-290.
• [55]Kumagai T, Muller CI, Desmond JC, Imai Y, Heber D, Koeffler HP: Scutellaria baicalensis, a herbal medicine: anti-proliferative and apoptotic activity against acute lymphocytic leukemia, lymphoma and myeloma cell lines. Leuk Res 2007, 31(4):523-530.
• [56]Jung HS, Kim MH, Gwak NG, Im YS, Lee KY, Sohn Y, Choi H, Yang WM: Antiallergic effects of Scutellaria baicalensis on inflammation in vivo and in vitro. J Ethnopharmacol 2012, 141(1):345-349.
• [57]Kim WK, Kim JH, Jeong Da H, Chun YH, Kim SH, Cho KJ, Chang MJ: Radish (Raphanus sativus L. leaf) ethanol extract inhibits protein and mRNA expression of ErbB(2) and ErbB(3) in MDA-MB-231 human breast cancer cells. Nutr Res Pract 2011, 5(4):288-293.
• [58]Papi A, Orlandi M, Bartolini G, Barillari J, Iori R, Paolini M, Ferroni F, Grazia Fumo M, Pedulli GF, Valgimigli L: Cytotoxic and antioxidant activity of 4-methylthio-3-butenyl isothiocyanate from Raphanus sativus L. (Kaiware Daikon) sprouts. J Agric Food Chem 2008, 56(3):875-883.
• [59]Yan Q, Li Y, Jiang Z, Sun Y, Zhu L, Ding Z: Antiproliferation and apoptosis of human tumor cell lines by a lectin (AMML) of Astragalus mongholicus. Phytomedicine 2009, 16(6–7):586-593.
• [60]Huang LH, Yan QJ, Kopparapu NK, Jiang ZQ, Sun Y: Astragalus membranaceus lectin (AML) induces caspase-dependent apoptosis in human leukemia cells. Cell Prolif 2012, 45(1):15-21.
• [61]Lam SK, Ng TB: First report of a haemagglutinin-induced apoptotic pathway in breast cancer cells. Biosci Rep 2010, 30(5):307-317.
• [62]Zhang M, Chiu LC, Cheung PC, Ooi VE: Growth-inhibitory effects of a beta-glucan from the mycelium of Poria cocos on human breast carcinoma MCF-7 cells: cell-cycle arrest and apoptosis induction. Oncol Rep 2006, 15(3):637-643.
• [63]Lee S, Ra J, Song JY, Gwak C, Kwon HJ, Yim SV, Hong SP, Kim J, Lee KH, Cho JJ, et al.: Extracts from Citrus unshiu promote immune-mediated inhibition of tumor growth in a murine renal cell carcinoma model. J Ethnopharmacol 2011, 133(3):973-979.
• [64]Yadav VR, Prasad S, Sung B, Kannappan R, Aggarwal BB: Targeting inflammatory pathways by triterpenoids for prevention and treatment of cancer. Toxins (Basel) 2010, 2(10):2428-2466.
• [65]Yong Y, Shin SY, Lee YH, Lim Y: Antitumor activity of deoxypodophyllotoxin isolated from Anthriscus sylvestris: Induction of G2/M cell cycle arrest and caspase-dependent apoptosis. Bioorg Med Chem Lett 2009, 19(15):4367-4371.
• [66]FDA: Guidance for industry: estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. Rockville: Pharmacology and Toxicology; 2005.
• [67]Contoli M, Message SD, Laza-Stanca V, Edwards MR, Wark PA, Bartlett NW, Kebadze T, Mallia P, Stanciu LA, Parker HL, et al.: Role of deficient type III interferon-lambda production in asthma exacerbations. Nat Med 2006, 12(9):1023-1026.
• [68]Chung KF: Cytokines in chronic obstructive pulmonary disease. Eur Respir J Suppl 2001, 34:50s-59s.
• [69]Hackett TL, Stefanowicz D, Aminuddin F, Sin DD, Connett JE, Anthonisen NR, Pare PD, Sandford AJ: Effect of gene environment interactions on lung function and cardiovascular disease in COPD. Int J Chron Obstruct Pulmon Dis 2011, 6:277-287.
• [70]De Torres JP, Pinto-Plata V, Casanova C, Mullerova H, Cordoba-Lanus E, Muros De Fuentes M, Aguirre-Jaime A, Celli BR: C-reactive protein levels and survival in patients with moderate to very severe COPD. Chest 2008, 133(6):1336-1343.
• [71]Hurst JR, Donaldson GC, Perera WR, Wilkinson TM, Bilello JA, Hagan GW, Vessey RS, Wedzicha JA: Use of plasma biomarkers at exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2006, 174(8):867-874.
• [72]Hurst JR, Perera WR, Wilkinson TM, Donaldson GC, Wedzicha JA: Systemic and upper and lower airway inflammation at exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2006, 173(1):71-78.
• [73]Wilkinson TM, Hurst JR, Perera WR, Wilks M, Donaldson GC, Wedzicha JA: Effect of interactions between lower airway bacterial and rhinoviral infection in exacerbations of COPD. Chest 2006, 129(2):317-324.
• [74]Yende S, Waterer GW, Tolley EA, Newman AB, Bauer DC, Taaffe DR, Jensen R, Crapo R, Rubin S, Nevitt M, et al.: Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects. Thorax 2006, 61(1):10-16.
• [75]Kuhn C 3rd, Homer RJ, Zhu Z, Ward N, Flavell RA, Geba GP, Elias JA: Airway hyperresponsiveness and airway obstruction in transgenic mice. Morphologic correlates in mice overexpressing interleukin (IL)-11 and IL-6 in the lung. Am J Respir Cell Mol Biol 2000, 22(3):289-295.