Evaluation of lung protection of Sanghuangporus sanghuang through TLR4/NF-κB/MAPK, keap1/Nrf2/HO-1, CaMKK/AMPK/Sirt1, and TGF-β/SMAD3 signaling pathways mediating apoptosis and autophagy

Biomed Pharmacother. 2023 Sep:165:115080. doi: 10.1016/j.biopha.2023.115080. Epub 2023 Jun 29.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a type of interstitial pneumonia characterized by chronic and progressive fibrosis with an unknown etiology. Previous pharmacological studies have shown that Sanghuangporus sanghuang possesses various beneficial properties including immunomodulatory, hepatoprotective, antitumor, antidiabetic, anti-inflammatory, and neuroprotective effects. This study used a bleomycin (BLM)-induced IPF mouse model to illustrate the possible benefits of SS in ameliorating IPF. BLM was administered on day 1 to establish a pulmonary fibrosis mouse model, and SS was administered through oral gavage for 21 d. Hematoxylin and eosin (H&E) and Masson's trichrome staining results showed that SS significantly reduced tissue damage and decreased fibrosis expression. We observed that SS treatment resulted in a substantial lowering in the level of pro-inflammatory cytokines like TGF-β, TNF-α, IL-1β, and IL-6 as well as MPO. In addition, we observed a notable increase in glutathione (GSH) levels. Western blot analysis of SS showed that it reduces inflammatory factors (TWEAK, iNOS, and COX-2), MAPK (JNK, p-ERK, and p-38), fibrosis-related molecules (TGF-β, SMAD3, fibronectin, collagen, α-SMA, MMP2, and MMP9), apoptosis (p53, p21, and Bax), and autophagy (Beclin-1, LC3A/B-I/II, and p62), and notably increases caspase 3, Bcl-2, and antioxidant (Catalase, GPx3, and SOD-1) levels. SS alleviates IPF by regulating the TLR4/NF-κB/MAPK, Keap1/Nrf2/HO-1, CaMKK/AMPK/Sirt1, and TGF-β/SMAD3 pathways. These results suggest that SS has a pharmacological activity that protects the lungs and has the potential to improve pulmonary fibrosis.

Keywords: Anti-inflammation; Apoptosis; Autophagy; Idiopathic pulmonary fibrosis; Oxidative stress; Sanghuangporus sanghuang.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Apoptosis
  • Autophagy
  • Basidiomycota
  • Bleomycin / pharmacology
  • Calcium-Calmodulin-Dependent Protein Kinase Kinase / metabolism
  • Disease Models, Animal
  • Fibrosis
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • Lung
  • Mice
  • NF-E2-Related Factor 2 / metabolism
  • NF-kappa B* / metabolism
  • Pulmonary Fibrosis* / chemically induced
  • Pulmonary Fibrosis* / drug therapy
  • Pulmonary Fibrosis* / metabolism
  • Signal Transduction
  • Sirtuin 1 / metabolism
  • Toll-Like Receptor 4 / metabolism
  • Transforming Growth Factor beta / metabolism

Substances

  • NF-kappa B
  • NF-E2-Related Factor 2
  • Toll-Like Receptor 4
  • AMP-Activated Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinase Kinase
  • Sirtuin 1
  • Kelch-Like ECH-Associated Protein 1
  • Transforming Growth Factor beta
  • Bleomycin
  • Sirt1 protein, mouse

Supplementary concepts

  • Sanghuangporus sanghuang