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

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−/−) 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

Effects of DISGT on body weights and liver weights. Mice (8 weeks old) were placed in four groups: normal diet (ND), high-fat diet (HFD), HFD with 300 mg/kg Do In Seung Gi-Tang (DISGT), and HFD with 10 mg/kg atorvastatin (statin). Experiments were carried out for 16 weeks. a Images of mice from all groups. b Body weights were measured every week for 16 weeks. c After 16 weeks of ND or HFD, liver tissues were collected and washed with cold phosphate-buffered solution, after which they were weighed. Values are mean ± SEM. **p < 0.01, ***p < 0.001 vs. ND; ###p < 0.001 vs. HFD
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Fig1: Effects of DISGT on body weights and liver weights. Mice (8 weeks old) were placed in four groups: normal diet (ND), high-fat diet (HFD), HFD with 300 mg/kg Do In Seung Gi-Tang (DISGT), and HFD with 10 mg/kg atorvastatin (statin). Experiments were carried out for 16 weeks. a Images of mice from all groups. b Body weights were measured every week for 16 weeks. c After 16 weeks of ND or HFD, liver tissues were collected and washed with cold phosphate-buffered solution, after which they were weighed. Values are mean ± SEM. **p < 0.01, ***p < 0.001 vs. ND; ###p < 0.001 vs. HFD

Mentions: The body weight, liver weight, and serum parameters were measured in mice. HFD-fed ApoE−/− mice showed significantly increased body weight compared with ND-fed mice (34.8 ± 0.59 vs. 49.7 ± 1.16 g, p < 0.001). However, treatment of HFD-fed mice with DISGT or statin decreased the body weight (Fig. 1a-b and Table 2; 36.7 ± 2.48 or 42.2 ± 1.24 g vs. HFD group; p < 0.001). Furthermore, the liver weights showed an increased in the HFD-fed ApoE−/− mice (p < 0.001), and the elevated liver weight was reduced by DISGT (Fig. 1c and Table 2; p < 0.001, versus HFD group). In addition, HFD-fed mice showed significantly higher serum levels of T-chole, LDL, TGs, glucose, AST, ALT, and creatinine than that of ND-fed mice. These levels were all significantly reduced by DISGT or statin treatment (Table 3).Fig. 1


The Korean herbal medicine, Do In Seung Gi-Tang, attenuates atherosclerosis via AMPK in high-fat diet-induced ApoE − / − mice
Effects of DISGT on body weights and liver weights. Mice (8 weeks old) were placed in four groups: normal diet (ND), high-fat diet (HFD), HFD with 300 mg/kg Do In Seung Gi-Tang (DISGT), and HFD with 10 mg/kg atorvastatin (statin). Experiments were carried out for 16 weeks. a Images of mice from all groups. b Body weights were measured every week for 16 weeks. c After 16 weeks of ND or HFD, liver tissues were collected and washed with cold phosphate-buffered solution, after which they were weighed. Values are mean ± SEM. **p < 0.01, ***p < 0.001 vs. ND; ###p < 0.001 vs. HFD
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5016892&req=5

Fig1: Effects of DISGT on body weights and liver weights. Mice (8 weeks old) were placed in four groups: normal diet (ND), high-fat diet (HFD), HFD with 300 mg/kg Do In Seung Gi-Tang (DISGT), and HFD with 10 mg/kg atorvastatin (statin). Experiments were carried out for 16 weeks. a Images of mice from all groups. b Body weights were measured every week for 16 weeks. c After 16 weeks of ND or HFD, liver tissues were collected and washed with cold phosphate-buffered solution, after which they were weighed. Values are mean ± SEM. **p < 0.01, ***p < 0.001 vs. ND; ###p < 0.001 vs. HFD
Mentions: The body weight, liver weight, and serum parameters were measured in mice. HFD-fed ApoE−/− mice showed significantly increased body weight compared with ND-fed mice (34.8 ± 0.59 vs. 49.7 ± 1.16 g, p < 0.001). However, treatment of HFD-fed mice with DISGT or statin decreased the body weight (Fig. 1a-b and Table 2; 36.7 ± 2.48 or 42.2 ± 1.24 g vs. HFD group; p < 0.001). Furthermore, the liver weights showed an increased in the HFD-fed ApoE−/− mice (p < 0.001), and the elevated liver weight was reduced by DISGT (Fig. 1c and Table 2; p < 0.001, versus HFD group). In addition, HFD-fed mice showed significantly higher serum levels of T-chole, LDL, TGs, glucose, AST, ALT, and creatinine than that of ND-fed mice. These levels were all significantly reduced by DISGT or statin treatment (Table 3).Fig. 1

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