juglanin and Pulmonary-Fibrosis

Idiopathic pulmonary fibrosis (IPF), characterized by excessive collagen deposition, is a progressive and typically fatal lung disease without effective therapeutic strategies. Juglanin, as a natural product mainly isolated from green walnut husks of Juglans mandshuric, has various bioactivities, including anti-oxidative, anti-inflammatory and anti-fibrotic effects. Stimulator of interferon genes (Sting) is a signaling molecule and plays an essential role in meditating fibrosis. However, the effects of Jug and Sting on pulmonary fibrosis are not fully understood. In this study, we investigated the role of Jug in bleomycin (BLM)-induced inflammation and fibrosis mouse model, as well as the underlying molecular mechanism. The results here indicated that Jug-treated mice exhibited a definitively improved survival rate than that of the BLM-challenged mice. Jug administration significantly alleviated neutrophil alveolar infiltration, lung vascular permeability and pro-inflammatory response in BLM mice. Subsequently, the pulmonary fibrosis induced by BLM was markedly attenuated by Jug through reducing the expression of fibrotic hallmarks, including transforming growth factor-β1 (TGF-β1), fibronectin, matrix metallo-proteinase-9 (MMP-9), α-smooth muscle actin (α-SMA) and collagen I. Importantly, we found that BLM mice showed higher expression levels of Sting in lung tissues, which were notably restrained by Jug treatment. The role of Jug in suppressing Sting was confirmed in TGF-β-incubated cells. Notably, the in vitro analysis further showed that Sting knockdown could ameliorate TGF-β-triggered collagen accumulation. In contrast, TGF-β-induced fibrosis was accelerated by Sting over-expression. Therefore, BLM may induce lung fibrosis through activating Sting signaling, and Jug could be used therapeutically to improve tissue repair and attenuate the intractable disease.

Topics: Actins; Animals; Bleomycin; Collagen Type I; Fibronectins; Gene Knockdown Techniques; Glycosides; Inflammation; Kaempferols; Male; Matrix Metalloproteinase 9; Membrane Proteins; Mice; Pulmonary Fibrosis; Signal Transduction; Survival Rate; Transforming Growth Factor beta1

Acute lung injury in children is a complication showing devastating disorders linked to fibrosis progression and inflammation response. Fibrosis and inflammation response are two markers for acute lung injury. Juglanin is a natural product mainly isolated from green walnut husks of Juglans mandshurica, which isconsidered as the functional composition among a series of compounds. It exhibited effective role in various diseases by inhibiting inflammation response. In our study, the protective effects and anti-inflammatory activity of juglanin were investigated in mice and lung cells treated by lipopolysaccharide (LPS) to reveal the possible mechanism by which juglanin attenuates acute lung injury. The mice were separated into four groups. The mouse model was established with 15 mg/kg LPS injection. Juglanin dramatically reduced the inflammation of cell infiltration. Compared to mice only treated with LPS, LPS-treated mice in the presence of juglanin developed less lung fibrosis with lower levels of α-smooth muscle-actin (α-SMA), collagen type I, collagen type III, and transforming growth factor-β1 (TGF-β1). Additionally, juglanin markedly downregulated inflammatory cytokine secretion and phosphorylated nuclear factor-κB (NF-κB) expression via inhibiting IKKα/IκBα signaling pathway. Our results indicate that juglanin has a protective role in LPS-triggered acute lung injury via suppression of fibrosis and inflammation response by NF-κB signaling pathways inactivation. Thus, juglanin may be a potential candidate as dietary supplement for acute lung injury for children in future.

Topics: Acute Lung Injury; Animals; Collagen Type I; Glycosides; Inflammation; Kaempferols; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Pulmonary Fibrosis; Signal Transduction; Transforming Growth Factor beta1