Abstract
BackgroundPuerarin, extracted from Radix puerariae, was reported to ameliorate airway inflammation, lung injury and lung fibrosis induced by paraquat (PQ) in mice. However, effects of Radix puerariae extracts (RPEs) on lung fibrosis or signalling pathways in PQ-induced lung injury have not been well studied. Therefore, the goals of our study were to investigate whether Radix puerariae extracts are antifibrotic in a paraquat (PQ) induced lung fibrosis model in mice and to propose possible mechanisms of action of the RPE effects.MethodsWe used a long-term exposure model of PQ-induced lung fibrosis in mice to evaluate effects of antioxidant-containing RPE. We examined effects of miR-21 on follistatin-like 1 (Fstl 1) pathways and oxidative stress in the lung. Gene expression levels of miR-21, Fstl 1, transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), collagen-1 and collagen III were measured by real-time PCR. Protein expression levels of Fstl 1(FSTL1), heme oxygenase-1 (HO-1), nuclear factor erythroid 2p45-related factor-2 (Nrf2), Smad2/3, p38MAPK, nuclear factor-κB 65 (NF-κB65), and matrix metalloproteinase-9 were detected by western blotting. FSTL1 andalpha-smooth muscle actin (α-SMA) in lung tissue were detected by immunohistochemistry. Malondialdehyde, superoxide dismutase (SOD), reduced (GSH) and oxidised (GSSH) glutathione and reactive oxygen species levels, hydroxyproline and total lung collagen were also determined.ResultsLong-term challenge with PQ enhanced miRNA-21 (miR-21), Fstl 1 pathways, oxidative stress and development of fibrotic features in the lungs. RPE reduced features of lung fibrosis by blocking Fstl 1 pathways and oxidative stress through decreased miR-21 expression. This was accompanied by suppression of CTGF, TGF-β1, vascular endothelial growth factor, collagen I, and collagen III. In addition, PQ-induced activation of NF-κB, Nrf2 and α-SMA were enhanced by puerarin. We also found that puerarin increased HO-1, SOD and GSH levels.ConclusionsThese findings demonstrated that RPEs blocked PQ-induced Fstl 1 pathways and oxidative stress by inhibiting miR-21 expression, leading to attenuation of PQ-induced lung fibrosis.
Highlights
Puerarin, extracted from Radix puerariae, was reported to ameliorate airway inflammation, lung injury and lung fibrosis induced by paraquat (PQ) in mice
Liu et al BMC Complementary and Alternative Medicine (2016) 16:11 (Continued from previous page). These findings demonstrated that Radix puerariae extract (RPE) blocked PQ-induced follistatin-like 1 (Fstl 1) pathways and oxidative stress by inhibiting miR-21 expression, leading to attenuation of PQ-induced lung fibrosis
Effect of miR-21 knockdown on miR-21 expression in lungs from PQ-treated mice We investigated effects of miR-21 knockdown on miR-21 expression in lung tissue from mice treated with PQ
Summary
Puerarin, extracted from Radix puerariae, was reported to ameliorate airway inflammation, lung injury and lung fibrosis induced by paraquat (PQ) in mice. Effects of Radix puerariae extracts (RPEs) on lung fibrosis or signalling pathways in PQ-induced lung injury have not been well studied. The goals of our study were to investigate whether Radix puerariae extracts are antifibrotic in a paraquat (PQ) induced lung fibrosis model in mice and to propose possible mechanisms of action of the RPE effects. The major cause of death by PQ poisoning is respiratory failure, a consequence of oxidative injury to the alveolar epithelium [2]. Its initial effects are pulmonary oedema, infiltration of inflammatory cells and damage to the alveolar epithelium, followed by the resulting lung fibrosis and respiratory failure [2,3,4]. Overall mortality remains above 50 % even in intensive care facilities [2]
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