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Chinese Medicine
Published in: Chinese Medicine 1/2020

Open Access 01-12-2020 | Smoking and Nicotine Detoxification | Research

Loki zupa alleviates inflammatory and fibrotic responses in cigarette smoke induced rat model of chronic obstructive pulmonary disease

Authors: Nabijan Mohammadtursun, Qiuping Li, Muhammadjan Abuduwaki, Shan Jiang, Hu Zhang, Jing Sun, Jingcheng Dong

Published in: Chinese Medicine | Issue 1/2020

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Abstract

Background

Loki zupa formula is kind of a traditional medicines which used to treat airway diseases, especially those caused by abnormal phlegm, such as cough, asthma and chronic bronchitis. The study aim was to explore the anti-inflammatory and anti-remodeling effects of Loki zupa by using a cigarette-smoke induced rat model of chronic obstructive pulmonary disease.

Methods

The rats were divided into five groups: the normal group, the model group, the LZ 4 g/kg and LZ8g/kg group, and the positive control group. Rats were exposed to cigarette smoke for 24 weeks to induce a COPD rat model. Lung function was assessed. Histopathological changes were recorded using Haematoxylin–eosin and Masson’s trichrome staining. Mucus hypersecretion was evaluated by PAS staining. Inflammatory factors were measured in blood serum and bronchial alveolar lavage fluid using an enzyme-linked immunosorbent assay. Malondialdehyde and superoxide dismutase and glutathione S-transferase levels were tested by biochemical methods. Gene expression patterns were evaluated using GN-GeneChip Clariom S Array for rat from Affymetrix. And top upregulated and downregulated genes validated by qPCR. And these genes was also compared with gene transcriptomic data from smoker patients with emphysema and non-smokers in GEO dataset. IL-6/PLAGA2A signalling protein expression was assessed by western blot and immunohistochemistry. TGF-β1and smad2/3 signalling expressions were analysed by western Blot.

Results

Loki zupa improved COPD rats lung function as compared to the model group and pathological changes including inflammatory cell infiltration and goblet cell metaplasia was alleviated in rats treated with Loki zupa Inflammatory factors IL-6, TNF-α, IL-1β and TGF-β1 decreased while significant increase was observed in blood serum IL-10 content in rats treated with Loki zupa. And IL-6 and TNF-α level in bronchial alveolar lavage fluid showed same expression trend in blood serum, while there was no change in MMP-9 content. It also increased antioxidant enzyme SOD and GPX activity while reducing the lipid peroxidation. Gene microarray analysis showed that there were 355 differentially expressed gene in LZ treated COPD rat lung as compared to model group. Both microarray and qPCR results showed that top differentially expressed genes nxt1 (up regulated) and pla2g2a (down regulated) expression were also reversed by LZ treatment. And protein expression level of IL-6 and pla2g2a was also elevated in CS exposed rats while significant reduction was observed in LZ treated rats. Accordingly, Loki zupa inhibited Collagen-1 upstream protein expression of TGF-β/smad2/3 signalling pathway.

Conclusion

These results demonstrated that Loki zupa showed protective effects in the lung of the COPD rat model. This mainly because of Loki zupa exerts anti-inflammatory effects by blocking IL-6/pla2g2a signalling and inhibiting inflammatory gene expression and attenuates fibrotic responses by inhibiting TGF-β/smad2/3 signalling pathway.
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Literature
1.
Vogelmeier CF, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 Report GOLD executive summary. Am J Respir Crit Care Med. 2017;195(5):557–82.PubMed
2.
Naghavi M, Abajobir AA, Abbafati C, Abbas KM, Abd-Allah F, Abera SF, Aboyans V, Adetokunboh O, Afshin A, Agrawal A, Ahmadi A. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390(10100):1151–210.
3.
Barnes PJ. New anti-inflammatory targets for chronic obstructive pulmonary disease. Nat Rev Drug Discov. 2013;12(7):543–59.PubMed
4.
Ding M, et al. Measuring airway remodeling in patients with different COPD staging using endobronchial optical coherence tomography. Chest. 2016;150(6):1281–90.PubMed
5.
Fischer BM, Pavlisko E, Voynow JA. Pathogenic triad in COPD: oxidative stress, protease-antiprotease imbalance, and inflammation. Int J Chron Obstruct Pulmon Dis. 2011;6:413–21.PubMedPubMedCentral
6.
Camilli AE, et al. Longitudinal changes in forced expiratory volume in one second in adults. Effects of smoking and smoking cessation. Am Rev Respir Dis. 1987;135(4):794–9.PubMed
7.
Scanlon PD, et al. Smoking cessation and lung function in mild-to-moderate chronic obstructive pulmonary disease. The Lung Health Study. Am J Respir Crit Care Med. 2000;161(2 Pt 1):381–90.PubMed
8.
Willemse BW, et al. The impact of smoking cessation on respiratory symptoms, lung function, airway hyperresponsiveness and inflammation. Eur Respir J. 2004;23(3):464–76.PubMed
9.
Oostwoud LC, et al. Apocynin and ebselen reduce influenza A virus-induced lung inflammation in cigarette smoke-exposed mice. Sci Rep. 2016;6:20983.PubMedPubMedCentral
10.
Ti H, et al. Targeted treatments for chronic obstructive pulmonary disease (COPD) using low-molecular-weight drugs (LMWDs). J Med Chem. 2019;62:5944–78.PubMed
11.
Chen T, et al. The protective effect of CDDO-Me on lipopolysaccharide-induced acute lung injury in mice. Int Immunopharmacol. 2015;25(1):55–64.PubMed
12.
Robinson MB, et al. IL-6 trans-signaling increases expression of airways disease genes in airway smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2015;309(2):L129–L138138.PubMedPubMedCentral
13.
Kitsiouli E, et al. Effect of azithromycin on the LPS-induced production and secretion of phospholipase A2 in lung cells. Biochim Biophys Acta. 2015;1852(7):1288–97.PubMed
14.
Wang M, et al. Group IIa secretory phospholipase A2 (sPLA2IIa) and progression in patients with lung cancer. Eur Rev Med Pharmacol Sci. 2014;18(18):2648–54.PubMed
15.
Al-Alawi M, Hassan T, Chotirmall S. Transforming growth factor β and severe asthma: a perfect storm. Respir Med. 2014;108(10):1409–23.PubMed
16.
Coker RK et al. Cellular localisation of transforming growth factor beta 1 and 3 gene expression in normal human lung and in the lungs of patients with pulmonary fibrosis. Thorax; 1998.
17.
U.M.V.E.C.o.C.M. Encyclopedia. Uyghur medical encyclopedia. Urumqi: Xinjiang people's publishing House; 2009. p. 204.
18.
Wei Y, et al. Loki zupa (Luooukezupa) decoction reduced airway inflammation in an OVA-induced asthma mouse model. Chin Med. 2016;11:22.PubMedPubMedCentral
19.
Lv Y, et al. A multicenter, randomized, double-blind, placebo-controlled study of the effects of Loki zupa in patients with chronic asthma. Front Pharmacol. 2018;9:351.PubMedPubMedCentral
20.
Yuan F, et al. JAX2, an ethanol extract of Hyssopus cuspidatus Boriss, can prevent bronchial asthma by inhibiting MAPK/NF-kappaB inflammatory signaling. Phytomedicine. 2019;57:305–14.PubMed
21.
Shomirzoeva O, et al. Chemical components of Hyssopus cuspidatus Boriss.: isolation and identification, characterization by HPLC-DAD-ESI-HRMS/MS, antioxidant activity and antimicrobial activity. Nat Prod Res. 2018;34:1–7.
22.
Min J, et al. Effects of Uygur medicine Hyssopus officinalis L on balance of Th1/Th2 and Th17/Treg of COPD Mice. World Sci Technol Mod Trad Chin Med. 2013;3:591–4.
23.
Wang G, et al. Baicalin exerts anti-airway inflammation and anti-remodelling effects in severe stage rat model of chronic obstructive pulmonary disease. Evid Based Complement Alternat Med. 2018;2018:7591348.PubMedPubMedCentral
24.
Wang G, et al. Establishment and evaluation of a rat model of sidestream cigarette smoke-induced chronic obstructive pulmonary disease. Front Physiol. 2018;9:58.PubMedPubMedCentral
25.
Verhamme FM, et al. Role of activin-A in cigarette smoke-induced inflammation and COPD. Eur Respir J. 2014;43(4):1028–41.PubMed
26.
Vestbo J, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013;187(4):347–65.PubMed
27.
Barnes PJ. The cytokine network in asthma and chronic obstructive pulmonary disease. J Clin Invest. 2008;118(11):3546–56.PubMedPubMedCentral
28.
Hubeau C, et al. Interleukin-6 neutralization alleviates pulmonary inflammation in mice exposed to cigarette smoke and poly(I:C). Clin Sci. 2013;125(10):483–93.PubMed
29.
Febbraio MA, et al. Is Interleukin-6 Receptor Blockade the Holy Grail for Inflammatory Diseases? Clin Pharmacol Ther. 2010;87(4):396–8.PubMed
30.
Kim DK, et al. Bronchoalveolar lavage fluid phospholipase A2 activities are increased in human adult respiratory distress syndrome. Am J Physiol Lung Cell Mol Physiol. 1995;269(1):109–18.
31.
Hite RD, et al. Hydrolysis of surfactant-associated phosphatidylcholine by mammalian secretory phospholipases A2. Am J Physiol. 1998;275(4):L740–L747747.PubMed
32.
Yu JA, et al. Knockdown of secretory phospholipase A2 IIa reduces lung cancer growth in vitro and in vivo. J Thorac Cardiovasc Surg. 2012;144(5):1185–91.PubMed
33.
34.
Barnes PJ. Corticosteroid resistance in patients with asthma and chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2013;131(3):636–45.PubMed
35.
Barnes PJ. How corticosteroids control inflammation: Quintiles Prize Lecture 2005. Br J Pharmacol. 2006;148(3):245–54.PubMedPubMedCentral
36.
Xu F, et al. Scutellaria baicalensis attenuates airway remodelling via PI3K/Akt/NF-kappaB pathway in cigarette smoke mediated-COPD rats model. Evid Based Complement Alternat Med. 2018;2018:1281420.PubMedPubMedCentral
37.
Ko JW, et al. Silibinin inhibits the fibrotic responses induced by cigarette smoke via suppression of TGF-beta1/Smad 2/3 signaling. Food Chem Toxicol. 2017;106(Pt A):424–9.PubMed
38.
Zhou R, et al. Liujunzi Tang, a famous traditional Chinese medicine, ameliorates cigarette smoke-induced mouse model of COPD. J Ethnopharmacol. 2016;193:643–51.PubMed
39.
Esa SA, et al. Study the level of sputum matrix metalloproteinase-9 and tissue inhibitor metaloprotienase-1 in patients with interstitial lung diseases. Egypt J Chest Dis Tuberc. 2016;65(1):303–9.
40.
Finlay GA, et al. Elevated levels of matrix metalloproteinases in bronchoalveolar lavage fluid of emphysematous patients. Thorax. 1997;52(6):502–6.PubMedPubMedCentral
41.
Thorley AJ, Tetley TD. Pulmonary epithelium, cigarette smoke, and chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2007;2(4):409–28.PubMedPubMedCentral
42.
Li J, et al. System biology analysis of long-term effect and mechanism of Bufei Yishen on COPD revealed by system pharmacology and 3-omics profiling. Sci Rep. 2016;6:25492.PubMedPubMedCentral
43.
Wright JL, Churg A. Animal models of cigarette smoke-induced COPD. Chest. 2002;122(6 Suppl):301S–6S.PubMed
44.
Barnes PJ, Shapiro SD, Pauwels RA. Chronic obstructive pulmonary disease: molecular and cellular mechanisms. Eur Respir J. 2003;22(4):672–88.PubMed
45.
Chunhua M, et al. Betulin inhibited cigarette smoke-induced COPD in mice. Biomed Pharmacother. 2017;85:679–86.PubMed
46.
Rogers DF. Mucus hypersecretion in COPD. Basel: Birkhäuser; 2011.
47.
Martin C, Frija-Masson J, Burgel PR. Targeting mucus hypersecretion: new therapeutic opportunities for COPD? Drugs. 2014;74(10):1073–89.PubMed
48.
Das B, Maity PC, Sil AK. Vitamin C forestalls cigarette smoke induced NF-kappaB activation in alveolar epithelial cells. Toxicol Lett. 2013;220(1):76–81.PubMed
49.
Cheng L, et al. Forsythiaside inhibits cigarette smoke-induced lung inflammation by activation of Nrf2 and inhibition of NF-kappaB. Int Immunopharmacol. 2015;28(1):494–9.PubMed
50.
51.
Baarsma HA, et al. Activation of WNT/beta-catenin signaling in pulmonary fibroblasts by TGF-beta(1) is increased in chronic obstructive pulmonary disease. PLoS ONE. 2011;6(9):e25450.PubMedPubMedCentral
52.
Zuniga JE, et al. Assembly of TbetaRI:TbetaRII:TGFbeta ternary complex in vitro with receptor extracellular domains is cooperative and isoform-dependent. J Mol Biol. 2005;354(5):1052–68.PubMed
Metadata
Title
Loki zupa alleviates inflammatory and fibrotic responses in cigarette smoke induced rat model of chronic obstructive pulmonary disease
Authors
Nabijan Mohammadtursun
Qiuping Li
Muhammadjan Abuduwaki
Shan Jiang
Hu Zhang
Jing Sun
Jingcheng Dong
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Chinese Medicine / Issue 1/2020
Electronic ISSN: 1749-8546
DOI
https://doi.org/10.1186/s13020-020-00373-3

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