gingerol and Acute-Lung-Injury

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.. 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.. 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.. 6-Gingerol attenuates sepsis-induced ALI by suppressing NLRP3 inflammasome activation via stimulation of Nrf2.

Topics: Acute Lung Injury; Animals; Inflammasomes; Inflammation; Interleukin-6; Lipopolysaccharides; Lung; NF-E2-Related Factor 2; NLR Family, Pyrin Domain-Containing 3 Protein; Rats; Rats, Sprague-Dawley; Sepsis; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Acute lung injury (ALI) and sepsis are complicated syndromes that are often left untreated in critically ill patients. 6-Gingerol is a phenolic phytochemical compound that is found in fresh ginger, has pharmacological effects against inflammation. This study explored the roles of 6-gingerol in a mouse model of acute lung injury caused by lipopolysaccharide (LPS) and RAW-264.7 cells inflammation. The LPS-induced animal model underwent histopathological examinations, and RAW-264.7 cells viability was determined by Cell counting Kit-8 (CCk-8) assay. Additionally, qRT-PCR, Immunofluorescence, Western blot, and ELISA were used in vivo and in vitro to identify inflammatory factors and proteins associated with NF-κB and MAPK signaling pathways. In a histological examination 6-gingerol exhibited protective effects. Moreover, 6-gingerol elevated cell viability and downregulated inflammatory factors Interlukin-1β (IL-1β), Interlukin-6 (IL-6) and Tumor necrosis factor-α (TNF-α) in LPS-treated RAW-264.7 cells. Furthermore, 6-gingerol decreased phosphorylation of P65, P38 and the level of JNK in NF-κB and MAPK pathways. Importantly, 6-gingerol increased transcript abundance of miR-322-5p which suppressed by LPS and miR-322-5p downregulation negated the protective functions of 6-gingerol. The protective activity of 6-gingerol was mediated by miR-322-5p up-regulation.

Topics: Acute Lung Injury; Animals; Humans; Inflammation; Lipopolysaccharides; Mice; MicroRNAs; NF-kappa B; RAW 264.7 Cells; Signal Transduction