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

Abstract

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

Acknowledgments

This work was supported by funds from the National “Major Science and Technology Project of Prevention and Treatment of AIDS, Viral Hepatitis, and Other Major Infectious Diseases” (grant no 2013ZX10005004), Major Project of Science and Technology of Shandong Province (grant no 2015ZDJS04001), Science & Technology Enterprise Technology Innovation Fund of Jiangsu Province (grant no BC2014172), and Small & Medium Enterprise Technology Innovation Project of Lianyungang City (grant no CK1333).

Disclosure

The authors report no conflicts of interest in this work.