Anti-atherosclerotic action of Ger-Gen-Chyn-Lian-Tang and AMPK-dependent lipid lowering effect in hepatocytes

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• 作者：Feng-Ming Ho^a ; ^b ; Yi-Hsiang Liao^c ; Ai-Jen Yang^c ; Pei-Dawn Lee Chao^d ; Yu-Chi Hou^d ; ^e ; Chen-Tsung Huang^c ; Shu-Rung Lin^f ; Kueir-Rarn Lee^g ; Kuo-Chin Huang^h ; Wan-Wan Lin^c ; ⁱ ; ^{wwllaura1119@ntu.edu.tw}
• 关键词：AMPK ; AMP-activated protein kinase ; ACC ; acetyl-CoA carboxylase ; BMDM ; bone marrow-derived macrophages ; FAS ; fatty acid synthase ; FG ; fasting glucose ; GGCLT ; Ger-Gen-Chyn-Lian-Tang ; HCD ; high cholesterol diet ; HDL ; high-density lipoprotein ; LDL ; low-densi
• 刊名：Journal of Ethnopharmacology
• 出版年：2012
• 期刊代码：26_03788741
• 类别：pha
• 出版时间：26 June, 2012
• 卷：142
• 期：1
• 页码：175-187
• 文件大小：1949 K

摘要

Ethnopharmacological relevance

The Ger-Gen-Chyn-Lian-Tang (GGCLT), an officially standardized mixture of Chinese herbal medicines, consists of Puerariae Radix, Scutellariae Radix, Coptidis Rhizoma and Glycyrrhizae Radix in a ratio of 8:3:3:2. In this study, we evaluated the benefits of GGCLT in atherosclerotic progression.

Methods

The major constituents of GGCLT were analyzed by HPLC. ApoE^{鈭?鈭?/sup> mice taken 0.15%cholesterol diet were orally given vehicle or GGCLT (2 g/kg/day) for 12 weeks. Serum levels of lipid and glucose were analyzed, and atherosclerosis was examined by histological analyses. Cultures of vascular smooth muscle cells, hepatocytes and bone marrow-derived macrophages were used to investigate the action mechanisms of GGCLT.}

Results

Our quantitation results indicated that GGCLT contains puerarin, daidzin, daidzein, baicalin, baicalein, wogonin, palmatine, coptisine, berberine and glycyrrhizin. GGCLT decreased serum levels of total cholesterol and LDL, but not TG and HDL in ApoE^{鈭?鈭?/sup> mice. In parallel, GGCLT treatment reduced atherosclerotic lesions and collagen expression in atheroma plaques. In vascular smooth muscle cells, GGCLT could reduce cell migration, but failed to affect cell viability and proliferation. In hepatocytes, GGCLT can reduce lipid accumulation, and this action was accompanied by the activation of AMPK, upregulation of PPARs, and downregulation of FAS. Pharmacological approach indicated that the latter two events contributing to the anti-lipogenesis is resulting from AMPK pathway, and the lipid lowering effect of GGCLT in hepatocytes is mediated by AMPK and PPAR伪 pathways. Meanwhile, two of the major components of GGCLT, berberine and puerarin, also activated AMPK and decreased lipid accumulation in hepatocytes with berberine of higher efficacy. Besides in hepatocytes, AMPK signaling was also activated by GGCLT in vascular smooth muscle cells and macrophages.}

Conclusions

These results demonstrate the anti-atherosclerotic action of Chinese medicine mixture GGCLT in ApoE^{鈭?鈭?/sup> atherosclerotic mouse model. Mechanistic study suggests that activation of AMPK and PPAR伪 in hepatocytes leading to a decrease of lipid formation contributes to the beneficial action of GGCLT in atherosclerosis treatment.}