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

Abstract

Ruijie Wang,1,2 Quan Li,1 Pengxin Wu,3 Ke Ren,3 Yan Li,1 Yang Wang,3 Huadong Zhu,1 Chuanzhu Lv2– 4 1Emergency Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 2Research Unit of Island Emergency Medicine, Chinese Academy of Medical Sciences (No. 2019RU013), Hainan Medical University, Haikou, People’s Republic of China; 3Emergency Medicine Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 4Key Laboratory of Emergency and Trauma of Ministry of Education, Hainan Medical University, Haikou, People’s Republic of ChinaCorrespondence: Chuanzhu Lv; Huadong Zhu, Email [email protected]; [email protected]: 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, sepsis, macrophage, nanoparticles, iron

Keywords

• capsaicin
• sepsis
• macrophage
• nanoparticles
• iron