Immune and Metabolic Regulation Mechanism of Dangguiliuhuang Decoction against Insulin Resistance and Hepatic Steatosis.

Immune and Metabolic Regulation Mechanism of Dangguiliuhuang Decoction against Insulin Resistance and Hepatic Steatosis.
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当归六黄汤抗胰岛素抵抗及肝脂肪变性的免疫代谢调节机制

DOI:
10.3389/fphar.2017.00445
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发表时间:
2017
影响因子:
5.6
通讯作者:
Xiang M
Xiang M
中科院分区:
医学2区
文献类型:
--
作者:
Cao H;Tuo L;Tuo Y;Xia Z;Fu R;Liu Y;Quan Y;Liu J;Yu Z;Xiang M

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当归六黄汤(Dangguiliuhuang汤剂,简称DGLHD)是一种以当归、黄芪、黄芩、黄连、黄芪、黄柏等为主要成分的中药方剂,用于治疗糖尿病及某些自身免疫性疾病。本研究通过体内外实验,探讨了当归补血汤抗胰岛素抵抗和脂肪肝的可能机制。我们的数据显示,DGLHD正常化葡萄糖和胰岛素水平,增加脂联素的表达,减少脂肪积累和脂肪生成,并促进葡萄糖摄取。代谢组学分析还表明,DGLHD降低了ob/ob小鼠肝脏和内脏脂肪组织(VAT)中的异亮氨酸、腺苷和胆固醇,增加了谷氨酰胺水平。重要的是,DGLHD促进促炎性细胞因子向抗炎性细胞因子的转变,抑制T淋巴细胞增殖,并增强调节性T细胞(Tcells)分化。DGLHD还可抑制树突状细胞(DCs)的成熟,抑制DCs刺激的T细胞增殖和DCs分泌IL-12 p70细胞因子,促进DCs与T细胞的相互作用。进一步的研究表明,DGLHD不仅能改善脂肪细胞和肝细胞的糖脂代谢,还能改变DCs和T细胞的PI 3 K/Akt信号通路,提高PPAR-γ的表达。总的来说,我们的研究结果表明,DGLHD发挥抗胰岛素抵抗和抗脂肪变性的作用,通过改善异常的免疫和代谢稳态。结论:DGLHD可能是治疗肥胖相关胰岛素抵抗和脂肪肝的新途径。
Dangguiliuhuang decoction (DGLHD) is a traditional Chinese medicine (TCM) formula, which mainly consists of angelica, radix rehmanniae, radix rehmanniae praeparata, scutellaria baicalensis, coptis chinensis, astragalus membranaceus, and golden cypress, and used for the treatment of diabetes and some autoimmune diseases. In this study, we explored the potential mechanism of DGLHD against insulin resistance and fatty liver in vivo and in vitro. Our data revealed that DGLHD normalized glucose and insulin level, increased the expression of adiponectin, diminished fat accumulation and lipogenesis, and promoted glucose uptake. Metabolomic analysis also demonstrated that DGLHD decreased isoleucine, adenosine, and cholesterol, increased glutamine levels in liver and visceral adipose tissue (VAT) of ob/ob mice. Importantly, DGLHD promoted the shift of pro-inflammatory to anti-inflammatory cytokines, suppressed T lymphocytes proliferation, and enhanced regulatory T cells (Tregs) differentiation. DGLHD also inhibited dendritic cells (DCs) maturation, attenuated DCs-stimulated T cells proliferation and secretion of IL-12p70 cytokine from DCs, and promoted the interaction of DCs with Tregs. Further studies indicated that the changed PI3K/Akt signaling pathway and elevated PPAR-γ expression were not only observed with the ameliorated glucose and lipid metabolism in adipocytes and hepatocytes, but also exhibited in DCs and T cells by DGLHD. Collectively, our results suggest that DGLHD exerts anti-insulin resistant and antisteatotic effects by improving abnormal immune and metabolic homeostasis. And DGLHD may be a novel approach to the treatment of obesity-related insulin resistance and hepatic steatosis.
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发表时间: 2013-06-05
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