Verbascoside and isoverbascoside ameliorate transforming growth factor?1-induced collagen expression by lung fibroblasts through Smad/ non-Smad signaling pathways

Aims: 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.Main methods: Transforming growth factor-beta 1 (TGF-beta 1) 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-beta 1-stimulated murine lung fibroblasts (MLg 2908) and also human lung fibroblasts (confirmed by immunostaining).Key findings: Neither VB nor isoVB had a cytotoxic effect on MLg 2908 fibroblasts. Both compounds (10 mu M) reduced intracellular reactive oxygen species and markedly attenuated collagen I expression in TGF-beta 1 (5 ng/ ml)-induced MLg 2908 cells compared to TGF-beta 1 alone. Both compounds suppressed the TGF-beta 1-induced phosphorylation of Smad2/3 and ERK/p38 mitogen-activated protein kinases (MAPKs). VB and isoVB, but not pirfenidone and nintedanib, inhibited TGF-beta 1-induced pSmad2/3, ERK/p38 MAPK, and collagen I expression. VB and isoVB also decreased collagen I deposition in TGF-beta 1-induced MLg 2908 cells. Only isoVB significantly suppressed collagen I deposition in TGF-beta 1-induced human pulmonary cells. Our results indicated that VB and isoVB may exert antifibrotic effects by inhibiting TGF-beta 1-induced collagen I expression via inhibition of oxidative stress and downregulation of the Smad/non-Smad pathway.Significance: The present findings suggest that VB or isoVB may be used as a supplement to alleviate PF.

Automated summary

VB and isoVB show potential as anti-fibrotic agents by inhibiting TGF-beta 1-induced collagen I expression through oxidative stress inhibition and downregulation of the Smad/non-Smad pathway.