ReferenceID 4731
Betulinic acid attenuated bleomycin-induced pulmonary fibrosis by effectively intervening Wnt/β-catenin signaling
Phytomedicine
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal and progressive fibrotic lung disease lacking a validated and effective therapy. Aberrant activation of the Wnt/beta-catenin signaling cascade plays the key role
Relationship Network
Interactive first-hop connections across herbs, ingredients, formulas, targets, diseases, symptoms, syndromes, evidence, and monographs.
Click a node to open it in a new tab
Ingredient: 1Reference: 1Links: 1
Arranging relationship network...
Record Fields
Scalar fields from the final reference record.
- Reference Id
- 4731
- Evidence Id
- 21321
- Core Evidence Id
- 21321
- Source Reference Id
- 2707
- Herb2 Reference Id
- HBREF003504
- Subject Paper Key
- HBIN018373_33341025
- Pubmed Id
- 33341025
- Doi
- 10.1016/j.phymed.2020.153428
- Paper Title
- Betulinic acid attenuated bleomycin-induced pulmonary fibrosis by effectively intervening Wnt/β-catenin signaling
- Paper Abstract
- BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal and progressive fibrotic lung disease lacking a validated and effective therapy. Aberrant activation of the Wnt/beta-catenin signaling cascade plays the key role in the pathogenesis of IPF. Betulinic acid is a natural pentacyclic triterpenoid molecule that has excellent antitumor and antiviral activities. HYPOTHESIS: We hypothesized that BA has an anti-pulmonary fibrosis effect mediated by the suppression of the Wnt/beta-catenin pathway. Study design Pulmonary fibrosis markers were detected in vitro and in vivo to confirm the antifibrotic effect of BA. The Wnt/beta-catenin pathway-related proteins were overexpressed to determine the effect of BA on Wnt signaling. METHODS AND RESULTS: BA dose-dependently inhibited Wnt3a-induced fibroblast activation in vitro. Moreover, BA decreased Wnt3a- and LiCl-induced transcriptional activity, as assessed by the TOPFlash assay in fibroblasts, and repressed the expression of the Wnt target genes cyclin D1, axin 2, and S100A4. Further investigation indicated that BA restrained the nuclear accumulation of beta-catenin, mainly by increasing the phospho-beta-catenin ratio (S33/S37/T41 and S45), inhibited the phosphorylation of DVL2 and LRP, and decreased the levels of Wnt3a and LRP6. In agreement with the results of the in vitro assays, the in vivo experiments indicated that BA significantly decreased bleomycin-induced pulmonary fibrosis in mice and suppressed myofibroblast activation by inhibiting Wnt/beta-catenin signaling. CONCLUSION: BA may directly interfere with the Wnt/beta-catenin pathway to subsequently repress myofibroblast activation and pulmonary fibrosis.
- Journal
- Phytomedicine
- Publish Year
- 2021
- Experiment Subject
- mouse
- Experiment Type
- Cell Experiment
- Phenotype Related
- Fibrotic Lung Disease; Idiopathic Pulmonary Fibrosis; Pulmonary Fibrosis; Anti-pulmonary Fibrosis
- Paper Title Cn
- Paper Title En
- Betulinic acid attenuated bleomycin-induced pulmonary fibrosis by effectively intervening Wnt/β-catenin signaling
- Bilingual Status
- semi_complete