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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.
Abbreviations
LPS, Lipopolysaccharide; Elisa, Enzyme-linked immunosorbent assay; NF-κB, Nuclear factor kappa-B; W/D, Wet-to-dry; ICU, Intensive care units; ARDS, Acute respiratory distress syndrome; Fe-CAP NPs, Iron-capsaicin-based nanoparticles; iNOS, Inducible nitric oxide synthase; IL-6, Interleukin-6; PVP, Polyvinylpyrrolidone; TNF-α, Tumor Necrosis Factor-α; TGF-β, Transforming Growth Factor-β; PBS, Phosphate-Buffered Saline; DMEM, Dulbecco’s Modified Eagle Medium; FBS, Fetal Bovine Serum; CCK-8, Cell Counting Kit 8; BCA, Bicinchoninic acid; EB, Exosmotic Evans Blue; LIS, The Lung Injury Score; i.p., Intraperitoneal; TEM, Transmission electron microscopy; SEM, Scanning electron microscope; XPS, X-ray photoelectron spectroscopy; MODS, Multiple organ dysfunction syndrome.
Acknowledgments
The authors thank the Chinese Academy of Medical Sciences for the support.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
The authors declare that they have no competing financial interest conflicts or personal relationships in this work.