Nucleosides isolated from Ophiocordyceps sinensis inhibit cigarette smoke extract-induced inflammation via the SIRT1–nuclear factor-κB/p65 pathway in RAW264.7 macrophages and in COPD mice
Authors Sun X, Dong Z, Li N, Feng X, Liu Y, Li A, Zhu X, Li C, Zhao Z
Received 28 April 2018
Accepted for publication 8 June 2018
Published 10 September 2018 Volume 2018:13 Pages 2821—2832
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Andrew Yee
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Chunxue Bai
Xiao Sun,1 Zhonghua Dong,1 Nan Li,1 Xiuli Feng,1 Yan Liu,1 Ang Li,1 Xiaosong Zhu,1 Chunyan Li,1 Zhongxi Zhao1–3
1School of Pharmaceutical Sciences, Shandong University, Jinan, People’s Republic of China; 2Shandong Engineering and Technology Research Center for Jujube Food and Drug, Jinan, People’s Republic of China; 3Shandong Provincial Key Laboratory of Mucosal and Transdermal Drug Delivery Technologies, Shandong Academy of Pharmaceutical Sciences, Jinan, People’s Republic of China
Background: Ophiocordyceps sinensis (C. sinensis) extracts have been found to have a therapeutic effect on patients with chronic obstructive pulmonary disease (COPD). Silent information regulator 1 (SIRT1) plays an important role in the regulation of inflammatory mediators and correlates with lung function and COPD exacerbations. The objective of this work was to explore the anti-inflammatory effect and preliminary pathways of nucleosides from cultured C. sinensis on RAW264.7 macrophages and COPD mice.
Materials and methods: The nucleosides were extracted from cultured C. sinensis powder and further purified by macroporous resin D101 and glucan G10 columns. Inflammation and oxidative stress models in RAW264.7 macrophages and in mice were established by injection of cigarette smoke extract (CSE). We then examined how the isolated nucleosides regulated the production of the associated inflammatory mediators in vitro and in vivo by enzyme-linked immunosorbent assay, reverse transcription polymerase chain reaction, and Western blot.
Results: The nucleosides inhibited inflammatory mediator expression of tumor necrosis factor-α, interleukin-6, interleukin-1β, and nitric oxide in both the CSE-stimulated RAW264.7 macrophages and mice. Moreover, the nucleosides elevated SIRT1 activation and suppressed nuclear factor-κB (NF-κB)/p65 activation in vitro and in vivo. Nucleoside treatment significantly decreased the levels of the inflammatory mediators in the bronchoalveolar lavage fluid (BALF) and serum of the CSE-induced mice. The nucleosides also altered the recruitment of inflammatory cells in BALF and improved characteristic features of the lungs in the CSE-induced mice.
Conclusion: These results show that the nucleosides suppressed COPD inflammation through the SIRT1–NF-κB/p65 pathway, suggesting that the nucleosides may be partly responsible for the therapeutic effects of cultured C. sinensis on COPD patients.
Keywords: Ophiocordyceps sinensis, nucleosides, COPD, anti-inflammatory, SIRT1, NF-κB/p65
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