Cordyceps sinensis inhibits airway remodeling in rats with chronic obstructive pulmonary disease

Yang,Lei; Jiao,Xingai; Wu,Jinxiang; Zhao,Jiping; Liu,Tian; Xu,Jianfeng; Ma,Xiaohui; Cao,Liuzao; Liu,Lin; Liu,Yahui; Chi,Jingyu; Zou,Minfang; Li,Shuo; Xu,Jiawei; Dong,Liang

doi:10.3892/etm.2018.5777

Cordyceps sinensis inhibits airway remodeling in rats with chronic obstructive pulmonary disease

Authors:
- Lei Yang
- Xingai Jiao
- Jinxiang Wu
- Jiping Zhao
- Tian Liu
- Jianfeng Xu
- Xiaohui Ma
- Liuzao Cao
- Lin Liu
- Yahui Liu
- Jingyu Chi
- Minfang Zou
- Shuo Li
- Jiawei Xu
- Liang Dong
View Affiliations

Affiliations: Department of Pulmonary Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Department of Tuberculosis, Shandong Provincial Chest Hospital, Jinan, Shandong 250013, P.R. China
Published online on: January 19, 2018 https://doi.org/10.3892/etm.2018.5777
Pages: 2731-2738
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Cordyceps sinensis is a traditional Chinese herbal medicine that has been used for centuries in Asia as a tonic to soothe the lung for the treatment of respiratory diseases. The aim of the present study was to determine the effects of C. sinensis on airway remodeling in chronic obstructive pulmonary disease (COPD) and investigate the underlying molecular mechanisms. Rats with COPD were orally administered C. sinensis at low, moderate or high doses (2.5, 5 or 7.5 g/kg/day, respectively) for 12 weeks. Airway tissue histopathology, lung inflammation and airway remodeling were evaluated. C. sinensis treatment significantly ameliorated airway wall thickening, involving collagen deposition, airway wall fibrosis, smooth muscle hypertrophy and epithelial hyperplasia in model rats with COPD. Additionally, C. sinensis administration in rats with COPD reduced inflammatory cell accumulation and decreased inflammatory cytokine production, including tumor necrosis factor‑α, interleukin‑8 and transforming growth factor (TGF)‑β1 in bronchoalveolar lavage fluid. Meanwhile, the increased levels of α‑smooth muscle actin and collagen I in the COPD group were also markedly decreased by C. sinensis treatment. Furthermore, compared with untreated rats with COPD, C. sinensis reduced the expression level of phosphorylated (p)‑Smad2, p‑Smad3, TGF‑β1 and its receptors, with the concomitant increased expression of Smad7 in the lungs of rats with COPD. These results indicated that treatment with C. sinensis may be a useful approach for COPD therapy.

View Figures

View References

1	Global Initiative for Chronic Obstructive Lung Disease 2016. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. https://goldcopd.org2016
2	Caramori G, Casolari P, Giuffrè S, Barczyk A, Adcock I and Papi A: COPD pathology in the small airways. Panminerva Med. 53:51–70. 2011.PubMed/NCBI
3	Decramer M, Janssens W and Miravitlles M: Chronic obstructive pulmonary disease. Lancet. 379:1341–1351. 2012. View Article : Google Scholar : PubMed/NCBI
4	Hirota N and Martin JG: Mechanisms of airway remodeling. Chest. 144:1026–1032. 2013. View Article : Google Scholar : PubMed/NCBI
5	Aoshiba K and Nagai A: Differences in airway remodeling between asthma and chronic obstructive pulmonary disease. Clin Rev Allergy Immunol. 27:35–43. 2004. View Article : Google Scholar : PubMed/NCBI
6	Barnes PJ: The cytokine network in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol. 41:631–638. 2009. View Article : Google Scholar : PubMed/NCBI
7	Hogg JC and Timens W: The pathology of chronic obstructive pulmonary disease. Annu Rev Pathol. 4:435–459. 2009. View Article : Google Scholar : PubMed/NCBI
8	Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, Cherniack RM, Rogers RM, Sciurba FC, Coxson HO and Paré PD: The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med. 350:2645–2653. 2004. View Article : Google Scholar : PubMed/NCBI
9	Churg A, Tai H, Coulthard T, Wang R and Wright JL: Cigarette smoke drives small airway remodeling by induction of growth factors in the airway wall. Am J Respir Crit Care Med. 174:1327–1334. 2006. View Article : Google Scholar : PubMed/NCBI
10	Bartram U and Speer CP: The role of transforming growth factor beta in lung development and disease. Chest. 125:754–765. 2004. View Article : Google Scholar : PubMed/NCBI
11	de Boer WI, van Schadewijk A, Sont JK, Sharma HS, Stolk J, Hiemstra PS and van Krieken JH: Transforming growth factor beta1 and recruitment of macrophages and mast cells in airways in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 158:1951–1957. 1998. View Article : Google Scholar : PubMed/NCBI
12	Takizawa H, Tanaka M, Takami K, Ohtoshi T, Ito K, Satoh M, Okada Y, Yamasawa F, Nakahara K and Umeda A: Increased expression of transforming growth factor-beta1 in small airway epithelium from tobacco smokers and patients with chronic obstructive pulmonary disease (COPD). Am J Respir Crit Care Med. 163:1476–1483. 2001. View Article : Google Scholar : PubMed/NCBI
13	Yang YC, Zhang N, Crombruggen K, Hu GH, Hong SL and Bachert C: Transforming growth factor-beta1 in inflammatory airway disease: A key for understanding inflammation and remodeling. Allergy. 67:1193–1202. 2012. View Article : Google Scholar : PubMed/NCBI
14	Chung A, Tai H, Coulthard T, Wang R and Wright JL: Cigarette smoke drives small airway remodeling by induction of growth factors in the airway wall. Am J Respir Crit Care Med. 174:1327–1334. 2006. View Article : Google Scholar : PubMed/NCBI
15	Qu ZH, Yang ZC, Chen L, Lv ZD, Yi MJ and Ran N: Inhibition airway remodeling and transforming growth factor-β1/Smad signaling pathway by astragalus extract in asthmatic mice. Int J Mol Med. 29:564–568. 2012. View Article : Google Scholar : PubMed/NCBI
16	Gao GX, Li QM and Shen HH: Effect of Astragali-Cordyceps Mixtura on TGF-beta/Smad signal pathway in the lung of asthma airway remodeling. J Ethnopharmacol. 13:68–74. 2009. View Article : Google Scholar
17	Nakao A, Afrakhte M, Morén A, Nakayama T, Christian JL, Heuchel R, Itoh S, Kawabata M, Heldin NE, Heldin CH and ten Dijke P: Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. Nature. 389:631–635. 1997. View Article : Google Scholar : PubMed/NCBI
18	Weiss A and Attisano L: The TGFbeta superfamily signaling pathway. Wiley Interdiscip Rev Dev Biol. 2:47–63. 2013. View Article : Google Scholar : PubMed/NCBI
19	Wu Y, Sun H, Qin F, Pan Y and Sun C: Effect of various extracts and a polysaccharide from the edible mycelia of Cordycepssinensis on cellular and humoral immune response against ovalbumin in mice. Phytother Res. 20:646–652. 2006. View Article : Google Scholar : PubMed/NCBI
20	Zou Y, Liu Y, Ruan M, Feng X, Wang J, Chu Z and Zhang Z: Cordyceps sinensis oral liquid prolongs the lifespan of the fruit fly, Drosophila melanogaster, by inhibiting oxidative stress. Int J Mol Med. 36:939–946. 2015. View Article : Google Scholar : PubMed/NCBI
21	Zhou X, Gong Z, Su Y, Lin J and Tang K: Cordyceps fungi: Natural products, pharmacological functions and developmental products. J Pharm Pharmacol. 61:279–291. 2009. View Article : Google Scholar : PubMed/NCBI
22	Das SK, Masuda M, Sakurai A and Sakakibara M: Medicinal uses of the mushroom Cordyceps militaris: Current state and prospects. Fitoterapia. 81:961–968. 2010. View Article : Google Scholar : PubMed/NCBI
23	An X, Zhang AL, May BH, Lin L, Xu Y and Xue CC: Oral Chinese herbal medicine for improvement of quality of life in patients with stable chronic obstructive pulmonary disease: A systematic review. J Altern Complement Med. 18:731–743. 2012. View Article : Google Scholar : PubMed/NCBI
24	Huang TT, Lai HC, Ko YF, Ojcius DM, Lan YW, Martel J, Young JD and Chong KY: Hirsutella sinensis mycelium attenuates bleomycin-induced pulmonary inflammation and fibrosis in vivo. Sci Rep. 5:152822015. View Article : Google Scholar : PubMed/NCBI
25	Liu A, Wu J, Li A, Bi W, Liu T, Cao L, Liu Y and Dong L: The inhibitory mechanism of Cordyceps sinensis on cigarette smoke extract-induced senescence in human bronchial epithelial cells. Int J Chron Obstruct Pulmon Dis. 11:1721–1731. 2016. View Article : Google Scholar : PubMed/NCBI
26	Peng J, Li X, Feng Q, Chen L, Xu L and Hu Y: Anti-fibrotic effect of Cordyceps sinensis polysaccharide: Inhibiting HSC activation, TGF-β1/Smad signalling, MMPs and TIMPs. Exp Biol Med. 238:668–677. 2013. View Article : Google Scholar
27	Pan MM, Zhang MH, Ni HF, Chen JF, Xu M, Phillips AO and Liu BC: Inhibition of TGF-β1/Smad signal pathway is involved in the effect of Cordyceps sinensis against renal fibrosis in 5/6 nephrectomy rats. Food Chem Toxicol. 58:487–494. 2013. View Article : Google Scholar : PubMed/NCBI
28	Qi Y, Shang JY, Ma LJ, Sun BB, Hu XG, Liu B and Zhang GJ: Inhibition of AMPK expression in skeletal muscle by systemic inflammation in COPD rats. Respir Res. 15:1562014. View Article : Google Scholar : PubMed/NCBI
29	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
30	Bensky D, Clavey S and Stöger E: Chinese Herbal Medicine: Materia Medica. Eastland Press; Seattle, Wash, USA: 2004
31	Caramori G, Kirkham P, Barczyk A, Di Stefano A and Adcock I: Molecular pathogenesis of cigarette smoking-induced stable COPD. Ann N Y Acad Sci. 1340:55–64. 2015. View Article : Google Scholar : PubMed/NCBI
32	Durham AL, Caramori G, Chung KF and Adcock IM: Targeted anti-inflammatory therapeutics in asthma and chronic obstructive lung disease. Transl Res. 167:192–203. 2016. View Article : Google Scholar : PubMed/NCBI
33	Barnes PJ, Shapiro SD and Pauwels RA: Chronic obstructive pulmonary disease: Molecular and cellular mechanisms. Eur Respir J. 22:672–688. 2003. View Article : Google Scholar : PubMed/NCBI
34	Ganesan S and Sajjan US: Repair and remodeling of airway epithelium after injury in chronic obstructive pulmonary disease. Curr Respir Care Rep. 2:2013. View Article : Google Scholar : PubMed/NCBI
35	Camara J and Jarai G: Epithelial-mesenchymal transition in primary human bronchial epithelial cells is Smad-dependent and enhanced by fibronectin and TNF-alpha. Fibrogenesis Tissue Repair. 3:22010. View Article : Google Scholar : PubMed/NCBI
36	Doerner AM and Zuraw BL: TGF-beta1 induced epithelial to mesenchymal transition (EMT) in human bronchial epithelial cells is enhanced by IL-1beta but not abrogated by corticosteroids. Respir Res. 10:1002009. View Article : Google Scholar : PubMed/NCBI
37	Huang TT, Chong KY, Ojcius DM, Wu YH, Ko YF, Wu CY, Martel J, Lu CC, Lai HC and Young JD: Hirsutella sinensis mycelium suppresses interleukin-1β and interleukin-18 secretion by inhibiting bothcanonical and non-canonical inflammasomes. Sci Rep. 3:13742013. View Article : Google Scholar : PubMed/NCBI
38	Park SY, Jung SJ, Ha KC, Sin HS, Jang SH, Chae HJ and Chae SW: Anti-inflammatory effects of Cordyceps mycelium (Paecilomyces hepiali, CBG-CS-2) in Raw264.7 murine macrophages. Orient Pharm Exp Med. 15:7–12. 2015. View Article : Google Scholar : PubMed/NCBI
39	Kuo YC, Tsai WJ, Wang JY, Chang SC, Lin CY and Shiao MS: Regulation of bronchoalveolar lavage fluids cell function by the immunomodulatory agents from Cordycepssinensis. Life Sci. 68:1067–1082. 2001. View Article : Google Scholar : PubMed/NCBI
40	Leask A and Abraham DJ: TGF-beta signaling and the fibrutic response. FASEB J. 18:816–827. 2004. View Article : Google Scholar : PubMed/NCBI
41	Jinnin M, Ihn H and Tamaki K: Characterization of SIS3, a novel specific inhibitor of smad3 and its effect on transforming growth factor-β1-induced extracellular matrix expression. Mol Pharmacol. 69:597–607. 2006. View Article : Google Scholar : PubMed/NCBI
42	Le AV, Cho JY, Miller M, McElwain S, Golgotiu K and Broide DH: Inhibition of allergen-induced airway remodeling in Smad 3-deficient mice. J Immunol. 178:7310–7316. 2007. View Article : Google Scholar : PubMed/NCBI
43	Guan S, Liu Q, Han F, Gu W, Song L, Zhang Y, Guo X and Xu W: Ginsenoside Rg1 ameliorates cigarette smoke-induced airway fibrosis by suppressing the TGF-β1/Smad pathway in vivo and in vitro. Biomed Res Int. 2017:65101982017. View Article : Google Scholar : PubMed/NCBI
44	Liu X, Hao B, Ma A, He J, Liu X and Chen J: The expression of NOX4 in smooth muscles of small airway correlates with the disease severity of COPD. Biomed Res Int. 2016:28918102016.PubMed/NCBI
45	Aschner Y and Downey GP: Transforming growth factor-β: Master regulator of the respiratory system in health and disease. Am J Respir Cell Mol Biol. 54:647–655. 2016. View Article : Google Scholar : PubMed/NCBI