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. 2019 Sep;234(9):15654-15667.
doi: 10.1002/jcp.28216. Epub 2019 Feb 11.

Galangin ameliorates cardiac remodeling via the MEK1/2-ERK1/2 and PI3K-AKT pathways

Hui-Bo Wang  1 , Si-Hui Huang  1 , Man Xu  1 , Jun Yang  2 , Jian Yang  2 , Ming-Xin Liu  1 , Chun-Xia Wan  1 , Hai-Han Liao  1 , Di Fan  1 , Qi-Zhu Tang  1
Affiliations

Galangin ameliorates cardiac remodeling via the MEK1/2-ERK1/2 and PI3K-AKT pathways

Hui-Bo Wang et al. J Cell Physiol. 2019 Sep.

Erratum in

Abstract

Cardiac remodeling is associated with inflammation and apoptosis. Galangin, as a natural flavonol, has the potent function of regulating inflammation and apoptosis, which are factors related to cardiac remodeling. Beginning 3 days after aortic banding (AB) or Sham surgery, mice were treated with galangin for 4 weeks. Cardiac remodeling was assessed according to echocardiographic parameters, histological analyses, and hypertrophy and fibrosis markers. Our results showed that galangin administration attenuated cardiac hypertrophy, dysfunction, and fibrosis response in AB mice and angiotensin II-treated H9c2 cells. The inhibitory action of galangin in cardiac remodeling was mediated by MEK1/2-extracellular-regulated protein kinases 1/2 (ERK1/2)-GATA4 and phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT)-glycogen synthase kinase 3β (GSK3β) activation. Furthermore, we found that galangin inhibited inflammatory response and apoptosis. Our findings suggest that galangin protects against cardiac remodeling through decreasing inflammatory responses and apoptosis, which are associated with inhibition of the MEK1/2-ERK1/2-GATA4 and PI3K-AKT-GSK3β signals.

Keywords: AKT; ERK1/2; GATA4; cardiac remodeling; fibrosis; galangin; hypertrophy.

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Conflict of interest statement

The authors declare that there are no conflict of interests.

Figures

Figure 1
Figure 1
Galangin attenuated cardiac hypertrophy and improved cardiac function induced by pressure overload in vivo. (a–c) Statistical results of HW/BW ratio, LW/BW ratio, and HW/TL ratio at 4 weeks after AB surgery (n = 10). (d) HE staining of Sham and AB mice at 4 weeks after surgery in treatment by vehicle and Galangin mice (n = 6); (e) Statistical results for the cross‐sectional area (n = 6). (f–h) The mRNA levels of hypertrophic markers (n = 6). (i–k) Echocardiographic parameters in galangin‐treated mice (n = 8). # p < 0.05 versus Sham group; *p < 0.05 or **p < 0.01, versus AB group. AB: aortic banding; HE: haematoxylin and eosin; HW/BW: heart weight/body weight; HW/TL: heart weight/tibia length; LW/BW: lung weight/body weight; mRNA: messenger RNA [Color figure can be viewed at wileyonlinelibrary.com]
Figure 2
Figure 2
Galangin attenuated cardiac fibrosis induced by pressure overload in vivo. (a,b) Representative PSR staining on histological sections of the LV and the statistical results (6 = 5). (c–e) Representative blots of TGF‐β1, Smad2 phosphorylation, and Smad2 from indicated groups (n = 6). (d) Real‐time PCR analyses of fibrosis‐related genes (n = 6). # p < 0.05 versus Sham group; *p < 0.05 or **p < 0.01, versus AB group. AB: aortic banding; LV: left ventricle; PCR: polymerase chain reaction; PSR, Picro‐Sirius red; TGF‐β1: transforming growth factor β1; α‐SMA: α‐smooth muscle actin [Color figure can be viewed at wileyonlinelibrary.com]
Figure 3
Figure 3
Galangin suppresses Ang II‐induced H9c2 cardiomyocyte hypertrophy. (a) Cell viability was accessed by the Cell Counting Kit‐8 assay. Cell Counting Kit‐8 assay was used to detect the cell viability of H9c2 cells in different concentrations (0, 5, 10, 25, 50, 75, 100, 150, 200, and 300 μM) of galangin (n = 6). (b, c) Immunofluorescence staining of α‐actinin and the cell surface area of H9c2 cells in the indicated groups (n = 6 samples, and 100 + cells per group). (d, f) H9c2 cells were stimulated with 1 μM Ang II and treated with galangin (0, 5, 10, 25, and 50 mM). The mRNA levels of ANP, BNP, and β‐MHC in H9c2 cells in each group (n = 6). # p < 0.05 versus Sham group or control group; *p < 0.05 or **p < 0.01, versus AB or Ang II group. AB: aortic banding; Ang II: angiotensin II; CCK8: Cell Counting Kit‐8; mRNA: messenger RNA [Color figure can be viewed at wileyonlinelibrary.com]
Figure 4
Figure 4
Galangin protected against cardiomyocyte apoptosis. (a) TUNEL staining exhibited the cellular apoptosis in vitro. (b) Counting of the TUNEL‐positive nuclear. (c–f) Representative western blot demonstrating Bcl2 and Bax protein expressions with the GAPDH in vitro and in vivo. #p < 0.05 versus Sham group or control group. *p < 0.05 or **p < 0.01, versus AB or Ang II group. AB: aortic banding; Ang II: angiotensin II; GAPDH: glyceraldehyde‐3‐phosphate dehydrogenase; TUNEL: transferase‐mediated dUTP nick end‐labeling [Color figure can be viewed at wileyonlinelibrary.com]
Figure 5
Figure 5
Galangin protected against cardiomyocyte inflammatory responses in vivo and in vitro. (a, b) The mRNA expression of inflammatory cytokines IL‐1 cytok‐6 in mouse heart. (c–h) Representative blots and quantification of P‐NFκB‐P65/T‐NFκB‐P65 and P‐IκBα/T‐IκBακ in vivo and in vitro. # p < 0.05 versus Sham group or control group. *p < 0.05 or **p < 0.01, versus AB or Ang II group. AB: aortic banding; Ang II: angiotensin II; mRNA: messenger RNA
Figure 6
Figure 6
Effect of galangin on the PI3K–AKT‐GSK3β signaling pathway. (a, b) Representative western blots for total and phosphorylation of PI3K, AKT, GSK3β. (c, d) Quantitative results of western blot (n = 5/ group). # p < 0.05 versus Sham group or control group. *p < 0.05 or **p < 0.01, versus AB or Ang II group. AB: aortic banding; AKT: protein kinase B; Ang II: angiotensin II; GSK3β: glycogen synthase kinase 3β; PI3K: phosphoinositide 3‐kinase
Figure 7
Figure 7
Effects of galangin on the MEK1/2–ERK1/2–GATA4 signaling pathway. (a, b) Representative western blots for total and phosphorylation of MEK1/2, ERK1/2, and GATA4. (c, d) Quantitative results of western blot (n = 5 per experimental group) # p < 0.05 versus the Sham group or the control group; *p< 0.05 or **p < 0.01, versus AB or Ang II group. AB: aortic banding; Ang II: angiotensin II; ERK1/2: extracellular‐regulated protein kinases 1/2
Figure 8
Figure 8
Galangin's molecular structure and proposed model of the effect of galangin on cardiac remodeling. (a) Representative galangin's molecular structure. (b) Representative proposed a model of the effect of galangin on cardiac remodeling. AKT: protein kinase B; Ang II: angiotensin II; ERK1/2: extracellular‐regulated protein kinases 1/2; PI3K: phosphoinositide 3‐kinase [Color figure can be viewed at wileyonlinelibrary.com]
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