lespenefril and Inflammation

Acute lung injury (ALI) causes severe and uncontrolled pulmonary inflammation and has high morbidity in dying patients.. This study aimed to evaluate the potential function of Kaempferitrin (Kae) and uncover its mechanisms in ALI.. We evaluated the role of Kae in ALI through the lipopolysaccharide (LPS)-induced histopathological changes, lung wet/dry (W/D) ratio, total bronchoalveolar lavage fluid (BALF) cells count, pulmonary inflammation, and the levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-1β. The effect of Kae on NF-κB signaling pathway was discovered through the protein expression levels of transcription factors p65, p-p65, IκBα, and p-IκBα by Western blot analysis.. The results showed that Kae could improve lung injury by reducing apoptosis, histopathological changes, and lung W/D ratio; more importantly, Kae enhanced the survival of ALI mice. Moreover, Kae relieved inflammation, as it reduced total BALF cells count, and deceased the levels of TNF-α, IL-6, and IL-1β in serum. In addition, Western blot analysis data suggested that Kae could decrease the protein expression levels of transcription factors p65, p-p65, IκB-α, and p-IκB-α, which were promoted by LPS.. The results of this study suggested that Kae could relieve LPS-induced ALI in mice and reduce inflammation and apoptosis through NF-κB pathway.

Topics: Acute Lung Injury; Animals; Humans; Inflammation; Interleukin-6; Lipopolysaccharides; Lung; Mice; NF-kappa B; NF-KappaB Inhibitor alpha; Pneumonia; Tumor Necrosis Factor-alpha

Rheumatoid arthritis (RA) is a complex chronic inflammatory disease that is associated with the aberrant activation of fibroblast-like synoviocytes (FLS). Kaempferitrin is a natural flavonoid glycoside that possesses anti-inflammatory bioactivity. However, the effect of kaempferitrin on RA has not yet been revealed. The aim of the present study was to investigate the effect of kaempferitrin on human RA-FLS MH7A cell line. We found that kaempferitrin inhibited proliferation and induced apoptosis of MH7A cells. Kaempferitrin decreased the levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, matrix metalloproteinase (MMP)-1, and MMP-3 in MH7A cells. Moreover, kaempferitrin blocked the activation of nuclear factor-κB (NF-κB) and protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathways. Furthermore, treatment with kaempferitrin decreased paw thickness and arthritis scores, and reduced the serum levels of IL-1β, IL-6, and TNF-α in a collagen-induced arthritis mouse model. In conclusion, kaempferitrin inhibited cell proliferation, induced cell apoptosis, and ameliorated inflammation of RA-FLS by suppressing the NF-κB and Akt/mTOR pathways.

Topics: Animals; Apoptosis; Arthritis, Experimental; Arthritis, Rheumatoid; Cell Proliferation; Cells, Cultured; Female; Fibroblasts; Humans; Inflammation; Interleukin-1beta; Kaempferols; Matrix Metalloproteinase 3; Mice; Mice, Inbred DBA; NF-kappa B; Proto-Oncogene Proteins c-akt; Synoviocytes; Tumor Necrosis Factor-alpha