Kurarinone Attenuates BLM-Induced Pulmonary Fibrosis via Inhibiting TGF-β Signaling Pathways

Abstract

Idiopathic pulmonary fibrosis (IPF) is a refractory interstitial lung disease for which there is no effective treatment. Although the pathogenesis of IPF is not fully understood, TGF-β and epithelial–mesenchymal transition (EMT) have been shown to be involved in the fibrotic changes of lung tissues. Kurarinone is a prenylated flavonoid isolated from Sophora Flavescens with antioxidant and anti-inflammatory properties. In this study, we investigated the effect of kurarinone on pulmonary fibrosis. Kurarinone suppressed the TGF-β-induced EMT of lung epithelial cells. To assess the therapeutic effects of kurarinone in bleomycin (BLM)-induced pulmonary fibrosis, mice were treated with kurarinone daily for 2 weeks starting 7 days after BLM instillation. Oral administration of kurarinone attenuated the fibrotic changes of lung tissues, including accumulation of collagen and improved mechanical pulmonary functions. Mechanistically, kurarinone suppressed phosphorylation of Smad2/3 and AKT induced by TGF-β1 in lung epithelial cells, as well as in lung tissues treated with BLM. Taken together, these results suggest that kurarinone has a therapeutic effect on pulmonary fibrosis via suppressing TGF-β signaling pathways and may be a novel drug candidate for pulmonary fibrosis.

Kurarinone alleviates hemin‐induced neuroinflammation and microglia‐mediated neurotoxicity by shifting microglial M1/M2 polarization via regulating the IGF1/PI3K/Akt signaling

“…Moreover, Kur elevated IGF1 abundance and activated the PI3K/Akt signaling pathway in hemin-treated HMC3 cells. Previous reports suggested Kur could inhibit the TGF-β signaling, 7 and inhibition of the TGF-β signaling could result in an increase of IGF-1 in activated microglia. 35 Hence, we hypothesized that the regulation of Kur on IGF1 expression in hemin-treated HMC3 cells was mediated by the TGF-β signaling.…”

“…It can inhibit cell immune response and resist oxidative stress 5,6 . In addition, Kur could diminish bleomycin‐tempted pulmonary fibrosis through constraining transforming growth factor beta (TGF‐β) signaling pathways 7 . Moreover, Sun et al confirmed that Kur might be a prospective medicine for the treatment of Parkinson's disease by modulating soluble epoxide hydrolase 8 .…”

“…5,6 In addition, Kur could diminish bleomycin-tempted pulmonary fibrosis through constraining transforming growth factor beta (TGF-β) signaling pathways. 7 Moreover, Sun et al confirmed that Kur might be a prospective medicine for the treatment of Parkinson's disease by modulating soluble epoxide hydrolase. 8 Besides, Nishikawa et al confirmed that Kur activated the activating transcription factor 4 (ATF4) by protein kinase-like ER kinase (PERK) and served as a cytostatic agent in cancer.…”

Theophylline Attenuates BLM-Induced Pulmonary Fibrosis by Inhibiting Th17 Differentiation

“…Consequently, TGF-β-induced EMT contributes to the development of IPF as the central activator. We previously showed that kurarinone has an anti-fibrotic effect using our experimental system based on the relationship between TGF-β and epithelial cells [ 62 ]. Using our experimental condition, theophylline decreased TGF-β-induced pro-fibrotic phenotypes in epithelial cells.…”

Berberine regulates pulmonary inflammatory microenvironment and decreases collagen deposition in response to bleomycin‐induced pulmonary fibrosis in mice

“…The expression levels of IL-8, IL-6, TNF-α, PDGF-AB and TGF-β1 (R&D Systems, Minneapolis, MN, USA) in bronchoalveolar lavage fluid, the content of HYP (MyBiosource, San Diego, CA, USA) per 500 mg of the lung tissue (to assess the collagen content), and the expression levels of total p38 MAPKα and p38 MAPKα (pT180/Y182) (ab221013, Abcam) were determined using an ELISA kit (Thermo Fisher Scientific, Waltham, MA, USA) at an absorbance of 450 nm, according to the manufacturer's instructions. 28 Two replicate wells were considered for each specimen. The expression level of each factor in each sample was determined using the calibration curve of absorbance versus concentration.…”