Effect of cryptotanshinone on airway inflammation and oxidative stress induced by cigarette smoke in mice_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

LIU Junhui , WU Yanqiu , HU Xueru ,  SHEN Yongchun , CHEN Lei

Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding?author：

SHEN Yongchun, Email: shen_yongchun@126.com

Keywords：

Cryptotanshinone; cigarette smoke; inflammation; oxidative stress

DOI：

10.7507/1671-6205.202111056

Video：

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Objectives To investigate the effects of cryptotanshinone (CTS) on cigarette smoke (CS) -induced airway inflammation and oxidative stress in mice and the possible mechanisms. Methods BALB/c mice were exposed to CS for 4 weeks to establish airway inflammation model. CTS was given by intraperitoneal injection before CS exposure at a dosage of 30 mg·kg^?1·d^?1 or 15 mg﹒kg^?1·d^?1. Bronchoalveolar lavage fluid (BALF) was acquired for cell counting and detection of pro-inflammatory cytokine [interleukine (IL)-17, monocyte chemotactic protein (MCP)-1, tumor necrosis factor (TNF)-α] levels. Lung tissue was collected for histological examination, superoxide dismutase (SOD) activities, malondialdehyde (MDA) levels, immunohistochemistry and polymerase chain reaction for Muc5ac detection, and western blot for lectin-like oxidized low-density lipoprotein-1 receptor (LOX-1) and nuclear factor (NF)-κB. Results CTS administration attenuated CS exposure induced thickening of the airway epithelium, peribronchial inflammatory cell infiltration, and lumen obstruction, increased numbers of total cells, macrophages, and neutrophils, and decreased the releases of IL-17, MCP-1, TNF-α in BALF of mice. CS exposure could induce the elevation in MDA levels and decrease in SOD activities, markers of oxidative stress. CTS could attenuate these changes. CTS also attenuated CS induced up-regulation of the protein levels of LOX-1 and phosphorylated p65, down-regulation of the levels of NF-κB inhibitor α. Conclusion CTS alleviates the airway inflammation, oxidative stress and mucus hypersecretion induced by CS, which may be through the regulation of LOX-1 and NF-κB signaling pathway.

Citation： LIU Junhui, WU Yanqiu, HU Xueru, SHEN Yongchun, CHEN Lei. Effect of cryptotanshinone on airway inflammation and oxidative stress induced by cigarette smoke in mice. Chinese Journal of Respiratory and Critical Care Medicine, 2022, 21(3): 189-194. doi: 10.7507/1671-6205.202111056 Copy

1.	中華醫學會呼吸病學分會慢性阻塞性肺疾病學組, 中國醫師協會呼吸醫師分會慢性阻塞性肺疾病工作委員會. 慢性阻塞性肺疾病診治指南(2021 年修訂版). 中華結核和呼吸雜志, 2021, 44(3): 170-205.
2.	Wang C, Xu J, Yang L, et al. Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health study): a national cross-sectional study. Lancet, 2018, 391(10131): 1706-1717.
3.	Zhou M, Wang H, Zeng X, et al. Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet, 2019, 394(10204): 1145-1158.
4.	Hikichi M, Mizumura K, Maruoka S, et al. Pathogenesis of chronic obstructive pulmonary disease (COPD) induced by cigarette smoke. J Thorac Dis, 2019, 11(Suppl 17): S2129-S2140.
5.	曾金, 張志榮, 繆萍, 等. 隱丹參酮的藥理作用研究進展. 中成藥, 2015, 37(6): 1309-1313.
6.	Liu H, Zhan X, Xu G, et al. Cryptotanshinone specifically suppresses NLRP3 inflammasome activation and protects against inflammasome-mediated diseases. Pharmacol Res, 2021, 164: 105384.
7.	Wang N, Dong X, Shi D, et al. Cryptotanshinone ameliorates placental oxidative stress and inflammation in mice with gestational diabetes mellitus. Arch Pharm Res, 2020, 43(7): 755-764.
8.	Tang Y, Chen YL, Chu Z, et al. Protective effect of cryptotanshinone on lipopolysaccharide-induced acute lung injury in mice. Eur J Pharmacol, 2014, 723: 494-500.
9.	Li J, Zheng M, Wang C, et al. Cryptotanshinone attenuates allergic airway inflammation through negative regulation of NF-κB and p38 MAPK. Biosci Biotechnol Biochem, 2020, 84(2): 268-278.
10.	Wu YH, Wu YR, Li B, et al. Cryptotanshinone: A review of its pharmacology activities and molecular mechanisms. Fitoterapia, 2020, 145: 104633.
11.	Barnes PJ. Targeting cytokines to treat asthma and chronic obstructive pulmonary disease. Nat Rev Immunol, 2018, 18(7): 454-466.
12.	向斌, 王瑋, 鄭勁平. 慢性阻塞性肺疾病氣道黏液高分泌研究進展. 國際呼吸雜志, 2019, 39(20): 1566-1571.
13.	饒敏, 陸月明. NF-κB 信號途徑在 COPD 中的研究進展. 國際呼吸雜志, 2017, 37(21): 1641-1645.
14.	Zhang P, Liu MC, Cheng L, et al. Blockade of LOX-1 prevents endotoxin-induced acute lung inflammation and injury in mice. J Innate Immun, 2009, 1(4): 358-365.
15.	Zou XZ, Gong ZC, Liu T, et al. Involvement of epithelial-mesenchymal transition afforded by activation of LOX-1/TGF-β1/KLF6 signaling pathway in diabetic pulmonary fibrosis. Pulm Pharmacol Ther, 2017, 44: 70-77.
16.	Wu Z, Sawamura T, Kurdowska AK, et al. LOX-1 deletion improves neutrophil responses, enhances bacterial clearance, and reduces lung injury in a murine polymicrobial sepsis model. Infect Immun, 2011, 79(7): 2865-2870.
17.	Deng W, Deng Y, Deng J, et al. Losartan attenuated lipopolysaccharide-induced lung injury by suppression of lectin-like oxidized low-density lipoprotein receptor-1. Int J Clin Exp Pathol, 2015, 8(12): 15670-15676.
18.	Ge X, Zhang DM, Li MM, et al. Microglial LOX-1/MAPKs/NF-κB positive loop promotes the vicious cycle of neuroinflammation and neural injury. Int Immunopharmacol, 2019, 70: 187-200.
19.	李俊峰, 王重陽, 徐暢, 等. 隱丹參酮通過抑制 p38 MAPK/NF-κB 通路改善哮喘氣道炎癥. 中藥新藥與臨床藥理, 2020, 31(1): 15-20.

1. 中華醫學會呼吸病學分會慢性阻塞性肺疾病學組, 中國醫師協會呼吸醫師分會慢性阻塞性肺疾病工作委員會. 慢性阻塞性肺疾病診治指南(2021 年修訂版). 中華結核和呼吸雜志, 2021, 44(3): 170-205.
2. Wang C, Xu J, Yang L, et al. Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health study): a national cross-sectional study. Lancet, 2018, 391(10131): 1706-1717.
3. Zhou M, Wang H, Zeng X, et al. Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet, 2019, 394(10204): 1145-1158.
4. Hikichi M, Mizumura K, Maruoka S, et al. Pathogenesis of chronic obstructive pulmonary disease (COPD) induced by cigarette smoke. J Thorac Dis, 2019, 11(Suppl 17): S2129-S2140.
5. 曾金, 張志榮, 繆萍, 等. 隱丹參酮的藥理作用研究進展. 中成藥, 2015, 37(6): 1309-1313.
6. Liu H, Zhan X, Xu G, et al. Cryptotanshinone specifically suppresses NLRP3 inflammasome activation and protects against inflammasome-mediated diseases. Pharmacol Res, 2021, 164: 105384.
7. Wang N, Dong X, Shi D, et al. Cryptotanshinone ameliorates placental oxidative stress and inflammation in mice with gestational diabetes mellitus. Arch Pharm Res, 2020, 43(7): 755-764.
8. Tang Y, Chen YL, Chu Z, et al. Protective effect of cryptotanshinone on lipopolysaccharide-induced acute lung injury in mice. Eur J Pharmacol, 2014, 723: 494-500.
9. Li J, Zheng M, Wang C, et al. Cryptotanshinone attenuates allergic airway inflammation through negative regulation of NF-κB and p38 MAPK. Biosci Biotechnol Biochem, 2020, 84(2): 268-278.
10. Wu YH, Wu YR, Li B, et al. Cryptotanshinone: A review of its pharmacology activities and molecular mechanisms. Fitoterapia, 2020, 145: 104633.
11. Barnes PJ. Targeting cytokines to treat asthma and chronic obstructive pulmonary disease. Nat Rev Immunol, 2018, 18(7): 454-466.
12. 向斌, 王瑋, 鄭勁平. 慢性阻塞性肺疾病氣道黏液高分泌研究進展. 國際呼吸雜志, 2019, 39(20): 1566-1571.
13. 饒敏, 陸月明. NF-κB 信號途徑在 COPD 中的研究進展. 國際呼吸雜志, 2017, 37(21): 1641-1645.
14. Zhang P, Liu MC, Cheng L, et al. Blockade of LOX-1 prevents endotoxin-induced acute lung inflammation and injury in mice. J Innate Immun, 2009, 1(4): 358-365.
15. Zou XZ, Gong ZC, Liu T, et al. Involvement of epithelial-mesenchymal transition afforded by activation of LOX-1/TGF-β1/KLF6 signaling pathway in diabetic pulmonary fibrosis. Pulm Pharmacol Ther, 2017, 44: 70-77.
16. Wu Z, Sawamura T, Kurdowska AK, et al. LOX-1 deletion improves neutrophil responses, enhances bacterial clearance, and reduces lung injury in a murine polymicrobial sepsis model. Infect Immun, 2011, 79(7): 2865-2870.
17. Deng W, Deng Y, Deng J, et al. Losartan attenuated lipopolysaccharide-induced lung injury by suppression of lectin-like oxidized low-density lipoprotein receptor-1. Int J Clin Exp Pathol, 2015, 8(12): 15670-15676.
18. Ge X, Zhang DM, Li MM, et al. Microglial LOX-1/MAPKs/NF-κB positive loop promotes the vicious cycle of neuroinflammation and neural injury. Int Immunopharmacol, 2019, 70: 187-200.
19. 李俊峰, 王重陽, 徐暢, 等. 隱丹參酮通過抑制 p38 MAPK/NF-κB 通路改善哮喘氣道炎癥. 中藥新藥與臨床藥理, 2020, 31(1): 15-20.

Chinese Journal of Respiratory and Critical Care Medicine

Effect of cryptotanshinone on airway inflammation and oxidative stress induced by cigarette smoke in mice

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