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Vol 61, No 1 (2023)
Original paper
Submitted: 2022-08-11
Accepted: 2023-01-24
Published online: 2023-02-03
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6-Gingerol attenuates sepsis-induced acute lung injury by suppressing NLRP3 inflammasome through Nrf2 activation

Quanli Pan1, Peng Liu1, Min Wan1
DOI: 10.5603/FHC.a2023.0002
·
Pubmed: 36734635
·
Folia Histochem Cytobiol 2023;61(1):68-80.
Affiliations
  1. Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei, China

open access

Vol 61, No 1 (2023)
ORIGINAL PAPERS
Submitted: 2022-08-11
Accepted: 2023-01-24
Published online: 2023-02-03

Abstract

Introduction. Sepsis is characterized by an overactive inflammatory response. Acute lung injury (ALI) is the most common type of organ injury in sepsis, with high morbidity and mortality. 6-Gingerol is the main bioactive compound of ginger, and it possesses anti-inflammatory bioactivity in different diseases. This study is aimed to explore the specific function of 6-Gingerol in sepsis-induced ALI. Material and methods. Lipopolysaccharide (LPS) was intraperitoneally injected into Sprague-Dawley rats for establishing the ALI models in vivo. The ALI rats were intraperitoneally injected with 20 mg/kg 6-Gingerol. The contents of oxidative stress markers malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were detected in the lung tissues of ALI rats. The concentrations of inflammatory factors [Tumor Necrosis Factor alpha (TNF-α), interleukin (IL)-6, and IL-1β] were measured by ELISA. Inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF) of rats was tested. Western blot was utilized to test the protein levels of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1) in lung tissues. Furthermore, immunohistochemical staining was applied for testing the expression of NLRP3 inflammasome in lung tissues. Results. The pathological changes in ALI rats were characterized by increased accumulation of inflammatory cells, alveolar hemorrhage, and pulmonary interstitial edema. However, the degree of pathological injury of lung tissues was significantly improved after 6-Gingerol treatment. Additionally, 6-Gingerol significantly attenuated the lung wet/dry ratio and protein permeability index (PPI) of LPS-induced rats. Furthermore, 6-Gingerol repressed oxidative stress and inflammatory reaction in LPS-induced rats by reducing the contents of MDA, GSH, SOD, TNF-α, IL-6, and IL-1β in the lung. LPS-induced infiltration of eosinophils, macrophages, neutrophils, and lymphocytes into lung was suppressed by 6-Gingerol administration. Moreover, 6-Gingerol activated Nrf2/HO-1 signaling and repressed LPS-induced‑NLRP3 inflammasome expression in lung tissues of LPS-induced rats. Intraperitoneal injection of ML385 (Nrf2 inhibitor) treatment into rats reversed the effects of 6-Gingerol on lung injury, inflammation, and oxidative stress in LPS-subjected rats. Conclusions. 6-Gingerol attenuates sepsis-induced ALI by suppressing NLRP3 inflammasome activation via stimulation of Nrf2.

Abstract

Introduction. Sepsis is characterized by an overactive inflammatory response. Acute lung injury (ALI) is the most common type of organ injury in sepsis, with high morbidity and mortality. 6-Gingerol is the main bioactive compound of ginger, and it possesses anti-inflammatory bioactivity in different diseases. This study is aimed to explore the specific function of 6-Gingerol in sepsis-induced ALI. Material and methods. Lipopolysaccharide (LPS) was intraperitoneally injected into Sprague-Dawley rats for establishing the ALI models in vivo. The ALI rats were intraperitoneally injected with 20 mg/kg 6-Gingerol. The contents of oxidative stress markers malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were detected in the lung tissues of ALI rats. The concentrations of inflammatory factors [Tumor Necrosis Factor alpha (TNF-α), interleukin (IL)-6, and IL-1β] were measured by ELISA. Inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF) of rats was tested. Western blot was utilized to test the protein levels of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1) in lung tissues. Furthermore, immunohistochemical staining was applied for testing the expression of NLRP3 inflammasome in lung tissues. Results. The pathological changes in ALI rats were characterized by increased accumulation of inflammatory cells, alveolar hemorrhage, and pulmonary interstitial edema. However, the degree of pathological injury of lung tissues was significantly improved after 6-Gingerol treatment. Additionally, 6-Gingerol significantly attenuated the lung wet/dry ratio and protein permeability index (PPI) of LPS-induced rats. Furthermore, 6-Gingerol repressed oxidative stress and inflammatory reaction in LPS-induced rats by reducing the contents of MDA, GSH, SOD, TNF-α, IL-6, and IL-1β in the lung. LPS-induced infiltration of eosinophils, macrophages, neutrophils, and lymphocytes into lung was suppressed by 6-Gingerol administration. Moreover, 6-Gingerol activated Nrf2/HO-1 signaling and repressed LPS-induced‑NLRP3 inflammasome expression in lung tissues of LPS-induced rats. Intraperitoneal injection of ML385 (Nrf2 inhibitor) treatment into rats reversed the effects of 6-Gingerol on lung injury, inflammation, and oxidative stress in LPS-subjected rats. Conclusions. 6-Gingerol attenuates sepsis-induced ALI by suppressing NLRP3 inflammasome activation via stimulation of Nrf2.

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Keywords

6-Gingerol; acute lung injury; sepsis; NLRP3 inflammasome; Nrf2

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Title

6-Gingerol attenuates sepsis-induced acute lung injury by suppressing NLRP3 inflammasome through Nrf2 activation

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 61, No 1 (2023)

Article type

Original paper

Pages

68-80

Published online

2023-02-03

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2960

Article views/downloads

878

DOI

10.5603/FHC.a2023.0002

Pubmed

36734635

Bibliographic record

Folia Histochem Cytobiol 2023;61(1):68-80.

Keywords

6-Gingerol
acute lung injury
sepsis
NLRP3 inflammasome
Nrf2

Authors

Quanli Pan
Peng Liu
Min Wan

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