Abstract：
Dahuang Huanglian Xiexin Decoction (DHXD) is the representative clinical formula for treating epigastric oppression. In this study, we aim to explore the effect of DHXD on obesity and attempt to investigate its potential mechanism. 3T3-L1 preadipocytes were differentiated and high-fat diet-induced obese rat model was established. DHXD was used for treatment and tunicamycin, the activator of endoplasmic reticulum (ER) stress, was adopted to investigate the related regulatory mechanism. Cell viability was evaluated using CCK-8 assay. Oil-Red O staining was performed to determine lipid accumulation. Glycerol production and Triglyceride content were measured using their commercial kits. Western blot was conducted to examine the expression of critical proteins. Results indicated that DHXD could greatly reduce intracellular lipid droplets and triglyceride in differentiated 3T3-L1 cells. Moreover, the elevated expression of mature adipocytes markers, PPARγ, aP2, during adipogenesis was decreased by DHXD treatment. In addition, DHXD aggravated the lipolysis in differentiated 3T3-L1 cells, as evidenced by the upregulated ATGL expression and the downregulated HSL expression. Besides, DHXD inhibited endoplasmic reticulum (ER) stress in 3T3-L1 cells. Further experiments indicated that the impacts of DHXD on adipocyte differentiation and lipid degradation were partly abolished by tunicamycin. Finally, DHXD alleviated lipid accumulation and ER stress in obese rats. In conclusion, DHXD ameliorates obesity via modulating adipocyte differentiation and lipid degradation through inhibiting ER stress.
摘要：
大黄黄连泻心汤（DHXD）是治疗上腹部压迫的代表性临床方剂。在这项研究中,本研究旨在探讨DHXD对肥胖的影响，并试图探讨其潜在的作用机制。分化3T3-L1前脂肪细胞,建立高脂饮食诱导的肥胖大鼠模型。DHXD用于治疗和衣霉素，内质网（ER）应激的激活剂，对相关监管机制进行了研究。使用CCK-8测定评价细胞活力。进行油红O染色以确定脂质积累。使用其商业试剂盒测量甘油产量和甘油三酯含量。进行Western印迹以检测关键蛋白的表达。结果表明，DHXD可以大大减少分化的3T3-L1细胞的细胞内脂滴和甘油三酸酯。此外，成熟脂肪细胞标志物的表达升高，PPARγ,在脂肪生成期间,通过DHXD处理降低了aP2。此外,DHXD加重分化的3T3-L1细胞的脂解,如ATGL表达上调和HSL表达下调所证明。此外,DHXD抑制3T3-L1细胞内质网应激。进一步的实验表明，衣霉素部分消除了DHXD对脂肪细胞分化和脂质降解的影响。最后,DHXD减轻肥胖大鼠的脂质积累和内质网应激。总之,DHXD通过抑制内质网应激调节脂肪细胞分化和脂质降解来改善肥胖。
