Verbascoside and isoverbascoside ameliorate transforming growth factor β1-induced collagen expression by lung fibroblasts through Smad/non-Smad signaling pathways
| Autor: | Chung-Yu, Chen, Hsuan-Yin, Tung, Yu-Fang, Tseng, Jau-Shyang, Huang, Li-Shian, Shi, Yi-Ling, Ye |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Pulmonary Fibrosis
Polyphenols Smad Proteins General Medicine Fibroblasts p38 Mitogen-Activated Protein Kinases General Biochemistry Genetics and Molecular Biology Transforming Growth Factor beta1 Mice Glucosides Phenols Transforming Growth Factor beta Animals Humans Collagen General Pharmacology Toxicology and Pharmaceutics Reactive Oxygen Species Lung Signal Transduction |
| Zdroj: | Life Sciences. 308:120950 |
| ISSN: | 0024-3205 |
| Popis: | Pulmonary fibrosis (PF) is a chronic, irreversible, and debilitating lung disease that typically leads to respiratory failure, and is a major cause of morbidity and mortality. Few drugs are effective for the treatment of patients with PF or for reducing the rate of disease progression.Transforming growth factor-β1 (TGF-β1) is a profibrotic cytokine that signals through Smad and non-Smad pathways. Verbascoside (VB) and isoverbascoside (isoVB) exhibit anti-oxidative and anti-inflammatory activities, however, their anti-fibrotic effects remain unclear. This study evaluated the effects of VB and isoVB on TGF-β1-stimulated murine lung fibroblasts (MLg 2908) and also human lung fibroblasts (confirmed by immunostaining).Neither VB nor isoVB had a cytotoxic effect on MLg 2908 fibroblasts. Both compounds (10 μM) reduced intracellular reactive oxygen species and markedly attenuated collagen I expression in TGF-β1 (5 ng/ml)-induced MLg 2908 cells compared to TGF-β1 alone. Both compounds suppressed the TGF-β1-induced phosphorylation of Smad2/3 and ERK/p38 mitogen-activated protein kinases (MAPKs). VB and isoVB, but not pirfenidone and nintedanib, inhibited TGF-β1-induced pSmad2/3, ERK/p38 MAPK, and collagen I expression. VB and isoVB also decreased collagen I deposition in TGF-β1-induced MLg 2908 cells. Only isoVB significantly suppressed collagen I deposition in TGF-β1-induced human pulmonary cells. Our results indicated that VB and isoVB may exert antifibrotic effects by inhibiting TGF-β1-induced collagen I expression via inhibition of oxidative stress and downregulation of the Smad/non-Smad pathway.The present findings suggest that VB or isoVB may be used as a supplement to alleviate PF. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect