Ginsenoside Rg1 Ameliorates Cigarette Smoke-Induced Airway Fibrosis by Suppressing the TGF-β1/Smad Pathway In Vivo and In Vitro

Abstract

Small airway fibrosis is a key pathological process accompanying chronic obstructive pulmonary disease (COPD) and includes fibroblast/myofibroblast transdifferentiation and excessive extracellular matrix deposition. Ginsenoside Rg1, one of the main active ingredients of Panax ginseng, has been shown to exert an antifibrotic effect in many tissues. However, little is known about the underlying mechanism and whether ginsenoside Rg1 can exert an effect on small airway fibrosis. We investigated the anti-small airway fibrosis effects of ginsenoside Rg1 in human embryonic lung fibroblasts and in COPD rats. We found that ginsenoside Rg1 effectively reduced the degree of pulmonary fibrosis, decreased the expression of α-smooth muscle actin, collagen I, and matrix metalloproteinase 9, and maintained the ratio of matrix metalloproteinase 9 to tissue inhibitor of metalloproteinase 1. Importantly, ginsenoside Rg1 significantly attenuated cigarette smoke extract-induced upregulation of transforming growth factor β1, TGF-β receptor I, phospho-Smad2, and phospho-Smad3. In addition, ginsenoside Rg1 mimicked the effect of SB525334, a TGF-β receptor I-Smad2/3 inhibitor. Collectively, these results suggest that ginsenoside Rg1 may suppress cigarette smoke-induced airway fibrosis in pulmonary fibroblasts and COPD rats by inhibiting the TGF-β1/Smad signaling pathway.

Ginsenoside Rg1 Alleviates Podocyte EMT Passage by Regulating AKT/GSK3 β/β‐Catenin Pathway by Restoring Autophagic Activity

“…Ginsenoside Rg1 is the main active ingredient of the ginseng rhizome extract and has antiapoptotic, antioxidant, antiinflammatory, and neuroprotective functions [17][18][19]. In addition, studies show that ginsenoside Rg1 can alleviate liver fibrosis, chronic obstructive pulmonary disease, and [20][21][22]. Previous studies show that ginsenoside Rg1 combined with astragaloside IV can protect renal function, which may be related to antioxidant stress and inhibition of TGF-β1/Smads pathway [23].…”

Panax ginseng and Panax quinquefolius : From pharmacology to toxicology

“…Hepatoprotection through the modulation of the Keap1-Nrf2-ARE pathway in preclinical models; amelioration of cigarette smoke-induced lung fibrosis by the downregulation of TGF-b/Smad pathway in pulmonary fibroblasts and COPD rats; induction of neural differentiation of ADSC through the microRNA-124 signaling; improvement of d-gal-induced POF by increasing both antioxidamt pathways and FSH receptor protein expression. Gao et al, 2017;Guan et al, 2017;Dong et al, 2017;He et al, 2017 Rg2 4,8,10,14-pentamethyl-2,3,5,6,7,9,11,12,13,15,16, 4,8,10,14-pentamethyl-2,3,5,6,7,9,11,12,13,15,16,17dodecahydro-1H-cyclopenta[a]phenanthren-6-yl]oxy]-6-(hydroxymethyl)oxane-3,4,5-triol Prevention of sleep deprivation-induced cognitive impairment in mice by reducing oxidative stress in cortex and hippocampus; reduction of oxidative stress-induced damage in rat primary astrocytes through the upregulation of MAPK and Nrf2/ARE signaling; osteoblast differentiation, osteogenic stimulation and antioxidant effect in mouse proteoblastic MC3T3-E1 cells via the BMP-2/Runx2 signaling pathways. Lu et al, 2017;Jung et al, 2016;Siddiqi et al, 2014 Rb1 plasma levels vis-a-vis with a significant increase in compound K plasma levels compared to those eating an Asian diet (Wan et al, 2017).…”

Combination of Ginsenoside Rg1 and Astragaloside IV reduces oxidative stress and inhibits TGF-β1/Smads signaling cascade on renal fibrosis in rats with diabetic nephropathy

“…Its proportion is the main criterion which determines the quality of P. ginseng . 10 Studies have reported that Ginsenoside Rg1 has a strong anti-oxidative and anti-fibrotic effect. 11 – 14 Astragaloside IV, a characteristic and active constituent of Radix Astragali , possesses many biological effects.…”