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The Korean herbal medicine, Do In Seung Gi-Tang, attenuates atherosclerosis via AMPK in high-fat diet-induced ApoE − / − mice

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ABSTRACT

Background: Do In Seung Gi-Tang (DISGT) is an herbal mixture of traditional Korean medicine that is composed of Rheum undulatum Linne, Prunus Persica (L.) Batsch, Conyza canadensis L., Cinnamomum Cassia Presl, and Glycytthiza uralensis Fischer (8: 6: 4: 4: 4 ratio). We investigated the effect of DISGT on vascular inflammation and lipid accumulation in apolipoprotein E-deficient (ApoE−/−) mice.

Methods: ApoE−/− mice that were fed a high-fat diet (HFD) were treated with DISGT (300 mg/kg/day) or statin (10 mg/kg/day) for 16 weeks. Serum lipid levels were analyzed. Oil Red O staining was used to evaluate atherosclerotic lesions and lipid accumulation in the aorta and liver, respectively. The expression of adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], and E-selectin), fatty acid synthase (FAS), adenosine monophosphate-activated protein kinase (AMPK), and acetyl-coA carboxylase (ACC) in the aorta or liver tissues was measured by western blot analysis. Lipid synthesis and inflammatory responses were assessed by immunohistochemistry and hematoxylin & eosin staining, respectively.

Results: Treatment of HFD-fed mice with DISGT significantly lowered body weight, liver weight, and the levels of lipids, including total cholesterol, low-density lipoprotein-cholesterol, and triglycerides. Glucose levels were also lowered. In the aorta, DISGT attenuated atherosclerotic lesions and reduced the expression of ICAM-1, VCAM-1, and E-selectin. Moreover, DISGT decreased lipid accumulation, inflammatory responses, and FAS levels, and it activated AMPK and reduced ACC expression in liver tissues.

Conclusions: The beneficial, anti-lipolytic, and anti-inflammatory effects of DISGT were mediated by the AMPK pathway. As a result, the expression of inflammatory factors was reduced. Our data provide evidence that DISGT may have strong therapeutic potential in treating vascular diseases, such as atherosclerosis.

No MeSH data available.


Related in: MedlinePlus

Effect of DISGT on reducing aortic lesions and expression of adhesion molecules in the aorta. a The aorta was collected from HFD-fed mice that were treated with DISGT or statin orally for 16 weeks. Representative photomicrographs of Oil Red O staining are shown. (Cross sections; ×100, above; ×200, under, magnification). b Quantification of Oil Red O-stained atherosclerotic lesion areas from each group. c Western blots of ICAM-1, VCAM-1, and E-selectin. d Densitometric analysis showing the relative protein expression levels of ICAM-1, VCAM-1, and E-selectin that were normalized to β-actin. Values are mean ± SEM. **p < 0.01, ***p < 0.001 vs. ND; #p < 0.05, ##p < 0.01, ###p < 0.001vs. HFD
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Fig2: Effect of DISGT on reducing aortic lesions and expression of adhesion molecules in the aorta. a The aorta was collected from HFD-fed mice that were treated with DISGT or statin orally for 16 weeks. Representative photomicrographs of Oil Red O staining are shown. (Cross sections; ×100, above; ×200, under, magnification). b Quantification of Oil Red O-stained atherosclerotic lesion areas from each group. c Western blots of ICAM-1, VCAM-1, and E-selectin. d Densitometric analysis showing the relative protein expression levels of ICAM-1, VCAM-1, and E-selectin that were normalized to β-actin. Values are mean ± SEM. **p < 0.01, ***p < 0.001 vs. ND; #p < 0.05, ##p < 0.01, ###p < 0.001vs. HFD

Mentions: The extent of atherosclerotic lesions in the aorta was determined by isolution analysis, and it was confined to the cross-section of the aortic root. Oli Red O staining was used to detect atherosclerotic plaques. The aortic root lesion area was markedly increased in HFD-fed mice (27.72 ± 2.87 mm2; p < 0.01), and it was significantly reduced by treatment with DISGT or statin (7.24 ± 1.81 mm2 or 11.90 ± 1.07 mm2; p < 0.01) (Fig. 2a and b). As demonstrated by western blot analysis, the expression of ICAM-1, VCAM-1, and E-selectin in HFD-fed mice was significantly increased compared with that in ND-fed mice. In contrast, DISGT- or statin-treated mice showed lower expression levels of ICAM-1, VCAM-1, and E-selectin compared with HFD-fed mice (Fig. 2c), and this decrease by DISGT was statistically significant (Fig. 2d).Fig. 2


The Korean herbal medicine, Do In Seung Gi-Tang, attenuates atherosclerosis via AMPK in high-fat diet-induced ApoE − / − mice
Effect of DISGT on reducing aortic lesions and expression of adhesion molecules in the aorta. a The aorta was collected from HFD-fed mice that were treated with DISGT or statin orally for 16 weeks. Representative photomicrographs of Oil Red O staining are shown. (Cross sections; ×100, above; ×200, under, magnification). b Quantification of Oil Red O-stained atherosclerotic lesion areas from each group. c Western blots of ICAM-1, VCAM-1, and E-selectin. d Densitometric analysis showing the relative protein expression levels of ICAM-1, VCAM-1, and E-selectin that were normalized to β-actin. Values are mean ± SEM. **p < 0.01, ***p < 0.001 vs. ND; #p < 0.05, ##p < 0.01, ###p < 0.001vs. HFD
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Related In: Results  -  Collection

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Fig2: Effect of DISGT on reducing aortic lesions and expression of adhesion molecules in the aorta. a The aorta was collected from HFD-fed mice that were treated with DISGT or statin orally for 16 weeks. Representative photomicrographs of Oil Red O staining are shown. (Cross sections; ×100, above; ×200, under, magnification). b Quantification of Oil Red O-stained atherosclerotic lesion areas from each group. c Western blots of ICAM-1, VCAM-1, and E-selectin. d Densitometric analysis showing the relative protein expression levels of ICAM-1, VCAM-1, and E-selectin that were normalized to β-actin. Values are mean ± SEM. **p < 0.01, ***p < 0.001 vs. ND; #p < 0.05, ##p < 0.01, ###p < 0.001vs. HFD
Mentions: The extent of atherosclerotic lesions in the aorta was determined by isolution analysis, and it was confined to the cross-section of the aortic root. Oli Red O staining was used to detect atherosclerotic plaques. The aortic root lesion area was markedly increased in HFD-fed mice (27.72 ± 2.87 mm2; p < 0.01), and it was significantly reduced by treatment with DISGT or statin (7.24 ± 1.81 mm2 or 11.90 ± 1.07 mm2; p < 0.01) (Fig. 2a and b). As demonstrated by western blot analysis, the expression of ICAM-1, VCAM-1, and E-selectin in HFD-fed mice was significantly increased compared with that in ND-fed mice. In contrast, DISGT- or statin-treated mice showed lower expression levels of ICAM-1, VCAM-1, and E-selectin compared with HFD-fed mice (Fig. 2c), and this decrease by DISGT was statistically significant (Fig. 2d).Fig. 2

View Article: PubMed Central - PubMed

ABSTRACT

Background: Do In Seung Gi-Tang (DISGT) is an herbal mixture of traditional Korean medicine that is composed of Rheum undulatum Linne, Prunus Persica (L.) Batsch, Conyza canadensis L., Cinnamomum Cassia Presl, and Glycytthiza uralensis Fischer (8: 6: 4: 4: 4 ratio). We investigated the effect of DISGT on vascular inflammation and lipid accumulation in apolipoprotein E-deficient (ApoE&minus;/&minus;) mice.

Methods: ApoE&minus;/&minus; mice that were fed a high-fat diet (HFD) were treated with DISGT (300&nbsp;mg/kg/day) or statin (10&nbsp;mg/kg/day) for 16&nbsp;weeks. Serum lipid levels were analyzed. Oil Red O staining was used to evaluate atherosclerotic lesions and lipid accumulation in the aorta and liver, respectively. The expression of adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], and E-selectin), fatty acid synthase (FAS), adenosine monophosphate-activated protein kinase (AMPK), and acetyl-coA carboxylase (ACC) in the aorta or liver tissues was measured by western blot analysis. Lipid synthesis and inflammatory responses were assessed by immunohistochemistry and hematoxylin &amp; eosin staining, respectively.

Results: Treatment of HFD-fed mice with DISGT significantly lowered body weight, liver weight, and the levels of lipids, including total cholesterol, low-density lipoprotein-cholesterol, and triglycerides. Glucose levels were also lowered. In the aorta, DISGT attenuated atherosclerotic lesions and reduced the expression of ICAM-1, VCAM-1, and E-selectin. Moreover, DISGT decreased lipid accumulation, inflammatory responses, and FAS levels, and it activated AMPK and reduced ACC expression in liver tissues.

Conclusions: The beneficial, anti-lipolytic, and anti-inflammatory effects of DISGT were mediated by the AMPK pathway. As a result, the expression of inflammatory factors was reduced. Our data provide evidence that DISGT may have strong therapeutic potential in treating vascular diseases, such as atherosclerosis.

No MeSH data available.


Related in: MedlinePlus