Limits...
Galangin attenuates airway remodelling by inhibiting TGF-β1-mediated ROS generation and MAPK/Akt phosphorylation in asthma.

Liu YN, Zha WJ, Ma Y, Chen FF, Zhu W, Ge A, Zeng XN, Huang M - Sci Rep (2015)

Bottom Line: Galangin significantly inhibited goblet cell hyperplasia, collagen deposition and α-SMA expression.Lowered level of TGF-β1 and suppressed expression of VEGF and MMP-9 were observed in BALF or lung tissue, implying that galangin has an optimal anti-remodelling effect in vivo.Consistently, the TGF-β1-induced proliferation of airway smooth muscle cells was reduced by galangin in vitro, which might be due to the alleviation of ROS levels and inhibition of MAPK pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

ABSTRACT
Galangin, a natural flavonol, has attracted much attention for its potential anti-inflammatory properties. However, its role in the regulation of airway remodelling in asthma has not been explored. The present study aimed to elucidate the effects of galangin on chronic inflammation and airway remodelling and to investigate the underlying mechanisms both in vivo and in vitro. Ovalbumin (OVA)-sensitised mice were administered with galangin 30 min before challenge. Our results showed that severe inflammatory responses and airway remodelling occurred in OVA-induced mice. Treatment with galangin markedly attenuated the leakage of inflammatory cells into bronchoalveolar lavage fluid (BALF) and decreased the level of OVA-specific IgE in serum. Galangin significantly inhibited goblet cell hyperplasia, collagen deposition and α-SMA expression. Lowered level of TGF-β1 and suppressed expression of VEGF and MMP-9 were observed in BALF or lung tissue, implying that galangin has an optimal anti-remodelling effect in vivo. Consistently, the TGF-β1-induced proliferation of airway smooth muscle cells was reduced by galangin in vitro, which might be due to the alleviation of ROS levels and inhibition of MAPK pathway. Taken together, the present findings highlight a novel role for galangin as a promising anti-remodelling agent in asthma, which likely involves the TGF-β1-ROS-MAPK pathway.

No MeSH data available.


Related in: MedlinePlus

Treatment with galangin inhibits the TGF-β1-induced ASMC proliferation.(A) Effect of stimulation with different concentrations of TGF-β1 on the proliferation of human ASMCs as assessed by the CCK-8 assay. (B) Effect of galangin on the viability of human ASMCs as assessed by the CCK-8 assay. (C-E) Effect of galangin on TGF-β1-stimulated human ASMCs as assessed by the CCK-8 and EdU assays. Scale bar: 100 μm. The values were presented as the means ± SEM of three replicates. *P < 0.05 compared with the control; #P < 0.05 compared with the TGF-β1 group. T1, TGF-β1, transforming growth factor-β1 (1 ng/mL); G, galangin (G0.1, 0.1 μM; G1, 1 μM; G10, 10 μM); DMSO, dimethylsulphoxide; ASMC, airway smooth muscle cell; CCK-8, cell counting kit; EDU, 5-ethynyl-2′-deoxyuridine.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4496730&req=5

f6: Treatment with galangin inhibits the TGF-β1-induced ASMC proliferation.(A) Effect of stimulation with different concentrations of TGF-β1 on the proliferation of human ASMCs as assessed by the CCK-8 assay. (B) Effect of galangin on the viability of human ASMCs as assessed by the CCK-8 assay. (C-E) Effect of galangin on TGF-β1-stimulated human ASMCs as assessed by the CCK-8 and EdU assays. Scale bar: 100 μm. The values were presented as the means ± SEM of three replicates. *P < 0.05 compared with the control; #P < 0.05 compared with the TGF-β1 group. T1, TGF-β1, transforming growth factor-β1 (1 ng/mL); G, galangin (G0.1, 0.1 μM; G1, 1 μM; G10, 10 μM); DMSO, dimethylsulphoxide; ASMC, airway smooth muscle cell; CCK-8, cell counting kit; EDU, 5-ethynyl-2′-deoxyuridine.

Mentions: The proliferation of human ASMCs was promoted by TGF-β1 stimulation (Fig. 6A). We determined the toxicity of galangin (0.1, 1, 10, 20, 40, 50 and 100 μM) on human ASMCs. The cell viabilities were 90% and 86% in the 10 μM-group at 24 h and 72 h (Fig. 6B). And galangin (0.1–10 μM) inhibited TGF-β1 (1 ng/mL, T1)-induced ASMC proliferation in a dose-dependent manner. Treatment with 10 μM galangin (G10) decreased T1-induced ASMC proliferation from 124% ± 8% to 101% ± 2% (P < 0.05); no significant effect was induced by 0.1 or 1 μM galangin (Fig. 6C). Furthermore, by using a 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay12, we observed that the number of cells incorporating EdU was notably increased after TGF-β1 stimulation compared to the control, whereas galangin pretreatment distinctly attenuated TGF-β1-induced proliferation (Fig. 6D,E).


Galangin attenuates airway remodelling by inhibiting TGF-β1-mediated ROS generation and MAPK/Akt phosphorylation in asthma.

Liu YN, Zha WJ, Ma Y, Chen FF, Zhu W, Ge A, Zeng XN, Huang M - Sci Rep (2015)

Treatment with galangin inhibits the TGF-β1-induced ASMC proliferation.(A) Effect of stimulation with different concentrations of TGF-β1 on the proliferation of human ASMCs as assessed by the CCK-8 assay. (B) Effect of galangin on the viability of human ASMCs as assessed by the CCK-8 assay. (C-E) Effect of galangin on TGF-β1-stimulated human ASMCs as assessed by the CCK-8 and EdU assays. Scale bar: 100 μm. The values were presented as the means ± SEM of three replicates. *P < 0.05 compared with the control; #P < 0.05 compared with the TGF-β1 group. T1, TGF-β1, transforming growth factor-β1 (1 ng/mL); G, galangin (G0.1, 0.1 μM; G1, 1 μM; G10, 10 μM); DMSO, dimethylsulphoxide; ASMC, airway smooth muscle cell; CCK-8, cell counting kit; EDU, 5-ethynyl-2′-deoxyuridine.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496730&req=5

f6: Treatment with galangin inhibits the TGF-β1-induced ASMC proliferation.(A) Effect of stimulation with different concentrations of TGF-β1 on the proliferation of human ASMCs as assessed by the CCK-8 assay. (B) Effect of galangin on the viability of human ASMCs as assessed by the CCK-8 assay. (C-E) Effect of galangin on TGF-β1-stimulated human ASMCs as assessed by the CCK-8 and EdU assays. Scale bar: 100 μm. The values were presented as the means ± SEM of three replicates. *P < 0.05 compared with the control; #P < 0.05 compared with the TGF-β1 group. T1, TGF-β1, transforming growth factor-β1 (1 ng/mL); G, galangin (G0.1, 0.1 μM; G1, 1 μM; G10, 10 μM); DMSO, dimethylsulphoxide; ASMC, airway smooth muscle cell; CCK-8, cell counting kit; EDU, 5-ethynyl-2′-deoxyuridine.
Mentions: The proliferation of human ASMCs was promoted by TGF-β1 stimulation (Fig. 6A). We determined the toxicity of galangin (0.1, 1, 10, 20, 40, 50 and 100 μM) on human ASMCs. The cell viabilities were 90% and 86% in the 10 μM-group at 24 h and 72 h (Fig. 6B). And galangin (0.1–10 μM) inhibited TGF-β1 (1 ng/mL, T1)-induced ASMC proliferation in a dose-dependent manner. Treatment with 10 μM galangin (G10) decreased T1-induced ASMC proliferation from 124% ± 8% to 101% ± 2% (P < 0.05); no significant effect was induced by 0.1 or 1 μM galangin (Fig. 6C). Furthermore, by using a 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay12, we observed that the number of cells incorporating EdU was notably increased after TGF-β1 stimulation compared to the control, whereas galangin pretreatment distinctly attenuated TGF-β1-induced proliferation (Fig. 6D,E).

Bottom Line: Galangin significantly inhibited goblet cell hyperplasia, collagen deposition and α-SMA expression.Lowered level of TGF-β1 and suppressed expression of VEGF and MMP-9 were observed in BALF or lung tissue, implying that galangin has an optimal anti-remodelling effect in vivo.Consistently, the TGF-β1-induced proliferation of airway smooth muscle cells was reduced by galangin in vitro, which might be due to the alleviation of ROS levels and inhibition of MAPK pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

ABSTRACT
Galangin, a natural flavonol, has attracted much attention for its potential anti-inflammatory properties. However, its role in the regulation of airway remodelling in asthma has not been explored. The present study aimed to elucidate the effects of galangin on chronic inflammation and airway remodelling and to investigate the underlying mechanisms both in vivo and in vitro. Ovalbumin (OVA)-sensitised mice were administered with galangin 30 min before challenge. Our results showed that severe inflammatory responses and airway remodelling occurred in OVA-induced mice. Treatment with galangin markedly attenuated the leakage of inflammatory cells into bronchoalveolar lavage fluid (BALF) and decreased the level of OVA-specific IgE in serum. Galangin significantly inhibited goblet cell hyperplasia, collagen deposition and α-SMA expression. Lowered level of TGF-β1 and suppressed expression of VEGF and MMP-9 were observed in BALF or lung tissue, implying that galangin has an optimal anti-remodelling effect in vivo. Consistently, the TGF-β1-induced proliferation of airway smooth muscle cells was reduced by galangin in vitro, which might be due to the alleviation of ROS levels and inhibition of MAPK pathway. Taken together, the present findings highlight a novel role for galangin as a promising anti-remodelling agent in asthma, which likely involves the TGF-β1-ROS-MAPK pathway.

No MeSH data available.


Related in: MedlinePlus