The Korean herbal medicine, Do In Seung Gi-Tang, attenuates atherosclerosis via AMPK in high-fat diet-induced ApoE(-/-) mice.
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.
Mibyeong Research Center, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 305-811, South Korea.|Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Gyeongnam, Yangsan, 626-870, South Korea.
Sun Haeng
SH
Park
Mibyeong Research Center, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 305-811, South Korea.
Yoon-Young
YY
Sung
Mibyeong Research Center, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 305-811, South Korea.
Seol
S
Jang
Mibyeong Research Center, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 305-811, South Korea.
Kyoung Jin
KJ
Nho
K-herb Research Center, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 305-811, South Korea.
Go Ya
GY
Choi
Mibyeong Research Center, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 305-811, South Korea. hkkim@kiom.re.kr.
Ho Kyoung
HK
Kim
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects; D008297:Male; D055670:Medicine, Korean Traditional; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*
D001057:Apolipoproteins E; D010936:Plant Extracts; D055372:AMP-Activated Protein Kinases
Adenosine monophosphate-activated protein kinase; Apolipoprotein E-deficient mice; Atherosclerosis; Do In Seung Gi-Tangm; Vascular inflammation