Journal
DRUG DESIGN DEVELOPMENT AND THERAPY
Volume 16, Issue -, Pages 1793-1809Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/DDDT.S361748
Keywords
G-Rb1; pulmonary fibrosis; NLRP3 inflammasome; macrophages
Categories
Funding
- National Key Research and Development Program of China, key special projects of major chronic non-communicable disease prevention and control [2016YFC1304600]
- Shandong Provincial Natural Science Foundation Youth Project [ZR2020QH289]
- National Natural Science Foundation of China youth project [82103803]
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G-Rb1 exerts anti-inflammatory and anti-fibrotic effects by suppressing the activation of NLRP3 inflammasome and NF-KB pathway, which may provide a potential therapeutic approach for idiopathic pulmonary fibrosis.
Purpose: Idiopathic pulmonary fibrosis is a chronic and irreversible fibrotic interstitial pneumonia of unknown etiology and therapeutic strategies are limited. Emerging evidence suggests that the continuous activation of the central nucleotide-binding oligomerization-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is involved in the pathogenesis of pulmonary fibrosis. Ginsenoside Rb1 (G-Rb1) is the most abundant component in the traditional Chinese herb ginseng and has antiinflammatory and anti-fibrotic activities. The purpose of this study was to explore whether G-Rb1 exerts anti-inflammatory and anti fibrotic activities in vivo and in vitro by suppressing the activation of the NLRP3 inflammasome and NF-KB pathway. Methods: Forty-eight male C57BL/6 mice were randomly divided into four groups (n=12/group) as follows: control, bleomycin (BLM), BLM/G-Rb1, and G-Rb1. A pulmonary fibrosis model was developed via an intratracheal injection of BLM. Six mice from each group were euthanized on days 3 and 21. The degree of pulmonary fibrosis was examined by histological evaluation and assessing alpha-smooth muscle actin levels. THP-1 cells were differentiated into macrophages, and stimulated by lipopolysaccharide and adenosine triphosphate. Activation of the NLRP3 inflammasome and NF-KB pathway was determined by Western blotting. Interleukin1 beta and interleukin-18 levels were measured by ELISA. MRC-5 cells were cultured in the conditioned medium of the treated macrophages, after which markers of myofibroblasts were determined by Western blotting. Results: G-Rb1 ameliorated BLM-induced pulmonary inflammation and fibrosis in mice, and suppressed NLRP3 inflammasome activation and the NF-KB pathway in lung tissues. Moreover, interleukin-1 beta secreted after NLRP3 inflammasome activation in macrophages promoted fibroblast differentiation. G-Rb1 inhibited lipopolysaccharide-and adenosine triphosphate-induced NLRP3 inflammasome activation in macrophages and disturbed the crosstalk between macrophages and fibroblasts. Conclusion: G-Rb1 ameliorates BLM-induced pulmonary inflammation and fibrosis by suppressing NLRP3 inflammasome activation and the NF-KB pathway. Hence, G-Rb1 is a potential novel therapeutic drug for idiopathic pulmonary fibrosis.
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