Fe-Capsaicin Nanozymes Attenuate Sepsis-Induced Acute Lung Injury via NF-κB Signaling

Int J Nanomedicine. 2024 Jan 3:19:73-90. doi: 10.2147/IJN.S436271. eCollection 2024.

Abstract

Background: In sepsis, the lungs are one of the most severely affected organs, usually resulting in acute lung injury (ALI). Capsaicin (CAP) is a natural compound found in chili peppers that has pain-relieving and anti-inflammatory properties. Here, we report that nanoparticles containing capsaicin and iron (Fe-CAP NPs) exhibited anti-inflammatory effects in the treatment of ALI.

Methods: The morphological characteristics of nanozymes were detected. RAW 264.7 cells were divided into four groups: control, lipopolysaccharide (LPS), CAP+LPS and Fe-CAP+LPS groups. The expression of inducible nitric oxide synthase (iNOS), transforming growth factor-β (TGF-β), and tumor necrosis factor-α (TNF-α) was assessed by immunofluorescence, Western blot, and enzyme-linked immunosorbent assay (ELISA). Nuclear factor kappa-B (NF-κB) expression was determined by Western blot. C57 mice were divided into control, LPS, CAP+LPS and Fe-CAP+LPS groups. Interleukin-6 (IL-6) and iNOS expression in the lung was detected by Western Blot. IL-6 and TNF-α expression in serum was detected by ELISA. Extravasated Evans blue, histopathological evaluation and wet-to-dry (W/D) weight ratio were used to assess pulmonary capillary permeability. The blood and major organs (heart, liver, spleen, lung and kidney) of mice were tested for the toxicity of Fe-CAP NPs.

Results: In the LPS group, TNF-α, iNOS, p-NF-κB and p-IKBα expression increased. However, their expression was significantly decreased in the Fe-CAP+LPS group. TGF-β expression showed the opposite trend. In vivo, IL-6 and iNOS expression was notably increased in the lungs of LPS group of mice but decreased with Fe-CAP pretreatment. Fe-CAP significantly ameliorated lung EB leakage, improved the histopathology of lung tissue and reduced the W/D weight ratio. The nanoparticles showed non-cytotoxicity, when studying these biological activities.

Conclusion: Fe-CAP NPs could alleviated inflammation by inhibiting the expression of pro-inflammatory factors in macrophages, increasing the expression of anti-inflammatory factors, and alleviating lung tissue damage.

Keywords: capsaicin; iron; macrophage; nanoparticles; sepsis.

MeSH terms

  • Acute Lung Injury* / drug therapy
  • Acute Lung Injury* / etiology
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Body Weight
  • Capsaicin
  • Interleukin-6
  • Lipopolysaccharides / toxicity
  • Mice
  • NF-kappa B
  • Sepsis* / complications
  • Sepsis* / drug therapy
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha

Substances

  • NF-kappa B
  • Capsaicin
  • Interleukin-6
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Anti-Inflammatory Agents
  • Transforming Growth Factor beta

Grants and funding

This study was funded by CAMS Innovation Fund for Medical Sciences (2019-I2M-5-023), National Natural Science Foundation of China (82303712), China Postdoctoral Science Foundation (2023M740520),Hainan Provincial Key Research and Development Project (ZDYF2020112) and Finance Science and Technology Program of Sichuan Province (2022YFS0602).