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

Feng Ming Ho, Yi Hsiang Liao, Ai Jen Yang, Pei Dawn Lee Chao, Yu Chi Hou, Chen Tsung Huang, Shu Rung Lin, Kueir Rarn Lee, Kuo Chin Huang, Wan Wan Lin

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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 -/- 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 -/- 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 PPARα 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 -/- atherosclerotic mouse model. Mechanistic study suggests that activation of AMPK and PPARα in hepatocytes leading to a decrease of lipid formation contributes to the beneficial action of GGCLT in atherosclerosis treatment.

Original languageEnglish
Pages (from-to)175-187
Number of pages13
JournalJournal of Ethnopharmacology
Volume142
Issue number1
DOIs
Publication statusPublished - Jun 26 2012

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AMP-Activated Protein Kinases
Hepatocytes
Berberine
Lipids
Peroxisome Proliferator-Activated Receptors
Apolipoproteins E
Vascular Smooth Muscle
Smooth Muscle Myocytes
Atherosclerosis
Macrophages
Pueraria
Scutellaria baicalensis
Glycyrrhizic Acid
Lipogenesis
Herbal Medicine
Atherosclerotic Plaques
Serum
LDL Cholesterol
Cell Movement
Cell Survival

Keywords

  • AMPK
  • ApoE knockout
  • Atherosclerosis
  • GGCLT
  • PPARs

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

Ho, F. M., Liao, Y. H., Yang, A. J., Lee Chao, P. D., Hou, Y. C., Huang, C. T., ... Lin, W. W. (2012). Anti-atherosclerotic action of Ger-Gen-Chyn-Lian-Tang and AMPK-dependent lipid lowering effect in hepatocytes. Journal of Ethnopharmacology, 142(1), 175-187. https://doi.org/10.1016/j.jep.2012.04.034

Anti-atherosclerotic action of Ger-Gen-Chyn-Lian-Tang and AMPK-dependent lipid lowering effect in hepatocytes. / Ho, Feng Ming; Liao, Yi Hsiang; Yang, Ai Jen; Lee Chao, Pei Dawn; Hou, Yu Chi; Huang, Chen Tsung; Lin, Shu Rung; Lee, Kueir Rarn; Huang, Kuo Chin; Lin, Wan Wan.

In: Journal of Ethnopharmacology, Vol. 142, No. 1, 26.06.2012, p. 175-187.

Research output: Contribution to journalArticle

Ho, FM, Liao, YH, Yang, AJ, Lee Chao, PD, Hou, YC, Huang, CT, Lin, SR, Lee, KR, Huang, KC & Lin, WW 2012, 'Anti-atherosclerotic action of Ger-Gen-Chyn-Lian-Tang and AMPK-dependent lipid lowering effect in hepatocytes', Journal of Ethnopharmacology, vol. 142, no. 1, pp. 175-187. https://doi.org/10.1016/j.jep.2012.04.034
Ho, Feng Ming ; Liao, Yi Hsiang ; Yang, Ai Jen ; Lee Chao, Pei Dawn ; Hou, Yu Chi ; Huang, Chen Tsung ; Lin, Shu Rung ; Lee, Kueir Rarn ; Huang, Kuo Chin ; Lin, Wan Wan. / Anti-atherosclerotic action of Ger-Gen-Chyn-Lian-Tang and AMPK-dependent lipid lowering effect in hepatocytes. In: Journal of Ethnopharmacology. 2012 ; Vol. 142, No. 1. pp. 175-187.
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AU - Yang, Ai Jen

AU - Lee Chao, Pei Dawn

AU - Hou, Yu Chi

AU - Huang, Chen Tsung

AU - Lin, Shu Rung

AU - Lee, Kueir Rarn

AU - Huang, Kuo Chin

AU - Lin, Wan Wan

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