Ganoderma lucidum polysaccharides ameliorate lipopolysaccharide-induced acute pneumonia via inhibiting NRP1-mediated inflammation

• Published in: Pharmaceutical biology 2022-12, Vol.60 (1), p.2201-2209
• Main Authors: Zhang, Xuelian, Wu, Daoshun, Tian, Yu, Chen, Xiangdong, Lan, Jin, Wei, Fei, Li, Ye, Luo, Yun, Sun, Xiaobo
• Format: Article
• Language: English
• Subjects: Animal models; anti-inflammatory; Apoptosis; Autophagy; BAX protein; Caspase-3; Cerebrospinal fluid; Colitis; COVID-19; Dexamethasone; Ganoderma lucidum; Ganodermataceae; Granulocyte-macrophage colony-stimulating factor; High-performance liquid chromatography; IL-1β; Infiltration; Inflammation; Interleukin 6; Lipopolysaccharides; Neuropilin; Pneumonia; pneumonocyte apoptosis; Polysaccharides; Trachea; Tumor necrosis factor-α; Western blotting
• ISSN: 1388-0209; 1744-5116
• DOI: 10.1080/13880209.2022.2142615

Ganoderma lucidum polysaccharides (GLP), from Ganoderma lucidum (Leyss. ex Fr.) Karst. (Ganodermataceae), are reported to have anti-inflammatory effects, including anti-neuroinflammation and anti-colitis. Nevertheless, the role of GLP in acute pneumonia is unknown. To explore the protective role of GLP against LPS-induced acute pneumonia and investigate possible mechanisms. GLP were extracted and used for high-performance liquid chromatography (HPLC) analysis after acid hydrolysis and PMP derivatization. Sixty C57BL/6N male mice were randomly divided into six groups: Sham, Model, LPS + GLP (25, 50 and 100 mg/kg/d administered intragastrically for two weeks) and LPS + dexamethasone (6 mg/kg/d injected intraperitoneally for one week). Acute pneumonia mouse models were established by intratracheal injection of LPS. Haematoxylin and eosin (H&E) staining was examined to evaluate lung lesions. ELISA and quantitative real-time PCR were employed to assess inflammatory factors expression. Western blots were carried out to measure Neuropilin-1 expression and proteins related to apoptosis and autophagy. GLP suppressed inflammatory cell infiltration. In BALF, cell counts were 1.1 × 10 6 (model) and 7.1 × 10 5 (100 mg/kg). Release of GM-CSF and IL-6 was reduced with GLP (25, 50 and 100 mg/kg) treatment. The expression of genes IL-1β, IL-6, TNF-α and Saa3 was reduced. GLP treatment also suppressed the activation of Neuropilin-1 (NRP1), upregulated the levels of Bcl2/Bax and LC3 and led to downregulation of the ratio C-Caspase 3/Caspase 3 and P62 expression. GLP could protect against LPS-induced acute pneumonia through multiple mechanisms: blocking the infiltration of inflammatory cells, inhibiting cytokine secretion, suppressing NRP1 activation and regulating pneumonocyte apoptosis and autophagy.