Astragaloside IV alleviates PM2.5-induced lung injury in rats by modulating TLR4/MyD88/NF-κB signalling pathway

• Published in: International immunopharmacology Vol. 91; p. 107290
• Main Authors: Wu, Yongcan, Xiao, Wei, Pei, Caixia, Wang, Mingjie, Wang, Xiaomin, Huang, Demei, Wang, Fei, Wang, Zhenxing
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2021; Elsevier BV
• Subjects: Alveoli; Animals; Anti-Inflammatory Agents - pharmacology; Antioxidants; Antioxidants - pharmacology; Astragaloside IV; Astragalus membranaceus; Bronchus; C-reactive protein; Cytokines; Cytokines - metabolism; Disease Models, Animal; Histology; Immunohistochemistry; In vivo methods and tests; Inflammation Mediators - metabolism; Inflammatory diseases; Injury analysis; Injury prevention; Interleukin 6; Lung - drug effects; Lung - metabolism; Lung - ultrastructure; Lung injury; Lung Injury - chemically induced; Lung Injury - metabolism; Lung Injury - pathology; Lung Injury - prevention & control; Lungs; Male; MyD88 protein; Myeloid Differentiation Factor 88 - metabolism; NF-kappa B - metabolism; NF-κB protein; Oxidative stress; Oxidative Stress - drug effects; Particulate Matter; Plant extracts; PM2.5; Proteins; Pulmonary Edema - chemically induced; Pulmonary Edema - metabolism; Pulmonary Edema - pathology; Pulmonary Edema - prevention & control; Rats; Rats, Sprague-Dawley; Rodents; Saponins - pharmacology; Signal Transduction; Signaling; Tissues; TLR4 protein; TLR4/MyD88/NF-κB signalling pathway; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Traditional Chinese medicine; Triterpenes - pharmacology; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Tumors; CRP; NCDs; DMSO; NS; HRP; MDA; Astragaloside IV; W/D; NF-κB; PRR; SD; ASH; PM2.5; TLR4/MyD88/NF-κB signalling pathway; ASL; Lung injury; AS IV; DAB; BALF; SOD; i.p; IL-6; i.t; AS; TNF-α; PMSF; CAT; GAPDH; COPD; ELISA
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2020.107290

•Airway instillation of PM2.5 standard can induce lung injury in rats.•The TLR4/MyD88/NF-κB signaling pathway is crucial in PM2.5-induced lung injury.•Astragaloside IV can modulates TLR4/MyD88/NF-kB signaling pathway.•Preventive administration of Astragaloside IV attenuates PM2.5-induced lung injury. Astragaloside IV (AS IV) is antioxidant and anti-inflammatory product, which is extracted from the Chinese herb Astragalus membranaceus. It is widely used in a variety of inflammatory diseases. The research was to explored the protective effects of AS IV against lung injury induced by particulate matter 2.5 (PM2.5) in vivo. Thirty-five male Sprague-Dawley rats were randomly divided into five groups (n=7 per group). (1) Normal saline group (NS), (2) AS IV group (AS) (100 mg/kg), (3) PM2.5 group (PM2.5), (4) PM2.5 + AS IV group (ASL) (50 mg/kg), and (5) PM2.5 + AS IVgroup (ASH) (100 mg/kg). Rats were pre-treated with AS IV intraperitoneally (50 and 100 mg/kg/day) for three days. Then, PM2.5 (7.5 mg/kg) was given by intratracheal instillation to induce lung injury. Six hours after PM2.5 stimulation, the rats were euthanized. Bronchoalveolar lavage fluid (BALF) was collected for assay of cytokines. Lung tissue was collected for oxidative stress, histology, immunohistochemistry, transmission electron microscope, and western blot analyses. AS IV alleviated PM2.5-induced lung injury by decreasing lung dry-wet ratio, reducing the level of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) in BALF, and reduced oxidative stress response in lung tissue. Western blot results revealed that AS-IV regulated the expression of TLR4/MyD88/NF-κB pathway proteins in lung tissues. AS IV mitigated PM2.5 induced lung injury by regulating the activity of TLR4/MyD88/NF-κB signalling pathway, reducing inflammatory and oxidative stress responses.