Department of Internal Medicine, Tao-Yuan General Hospital Department of Health the Executive Yuan, Taoyuan, Taiwan.
J Ethnopharmacol. 2012 Jun 26;142(1):175-87. doi: 10.1016/j.jep.2012.04.034. Epub 2012 Apr 21.
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.
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.
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.
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.
葛根芩连汤（GGCLT）是一种由葛根、黄芩、黄连和甘草以 8:3:3:2 的比例组成的中药标准化复方制剂。本研究评价了 GGCLT 对动脉粥样硬化进展的益处。
采用 HPLC 法分析 GGCLT 的主要成分。给予载脂蛋白 E 基因敲除（ApoE-/-）小鼠 0.15%胆固醇饮食，同时给予 vehicle 或 GGCLT（2 g/kg/d），连续灌胃 12 周。检测血清中脂质和葡萄糖水平，通过组织学分析检测动脉粥样硬化情况。采用血管平滑肌细胞、肝细胞和骨髓源性巨噬细胞培养方法，探讨 GGCLT 的作用机制。
定量结果表明，GGCLT 含有葛根素、大豆苷、大豆苷元、黄芩苷、黄芩素、汉黄芩素、黄连碱、小檗碱、甘草酸。GGCLT 降低 ApoE-/-小鼠血清总胆固醇和 LDL 水平，但不降低 TG 和 HDL。同时，GGCLT 治疗可减少动脉粥样硬化病变和斑块中胶原的表达。在血管平滑肌细胞中，GGCLT 可减少细胞迁移，但不影响细胞活力和增殖。在肝细胞中，GGCLT 可减少脂质堆积，这一作用伴随着 AMPK 的激活、PPARs 的上调和 FAS 的下调。药理学方法表明，后两个事件导致的抗脂生成作用是通过 AMPK 途径，GGCLT 对肝细胞的降脂作用是通过 AMPK 和 PPARα 途径介导的。同时，GGCLT 的两种主要成分黄连碱和葛根素也能激活 AMPK，降低肝细胞中的脂质堆积，其中黄连碱的效果更高。除了在肝细胞中，AMPK 信号也被 GGCLT 在血管平滑肌细胞和巨噬细胞中激活。
这些结果表明，中药复方 GGCLT 在 ApoE-/-动脉粥样硬化小鼠模型中具有抗动脉粥样硬化作用。机制研究表明，AMPK 和 PPARα 在肝细胞中的激活导致脂质生成减少，这有助于 GGCLT 在动脉粥样硬化治疗中的有益作用。
