Zhang Ruiyao, Zhang Yu, Xi Xi, Du Pengcheng, Guo Chao, Zhang Yanying, Song Bing, Xu Xiaoyan, Ni Zhitao, Wang Yongfeng, Bai Min
Gansu University of Chinese Medicine, Lanzhou, China.
Gansu Provincial Technical Center for Laboratory Animals, Lanzhou, China.
Front Endocrinol (Lausanne). 2025 Oct 8;16:1652703. doi: 10.3389/fendo.2025.1652703. eCollection 2025.
Dahuang ()-Huanglian () (DHHL), has been shown to effectively treat obesity caused by dietary irregularities. Nevertheless, the fundamental process driving this phenomenon has yet to be elucidated.
The chemical constituents of DHHL were analyzed using UPLC-MS/MS. An obesity model was established in rats by high-fat diet (HFD) induction and verified accordingly. Obese rats were administered various doses of DHHL. Detect and record the metabolic indicators of rats in each group. Transcriptomic analysis was used to evaluate the influence of DHHL on gene expression in obese rats. H&E staining and transmission electron microscopy (TEM) was used to observe the morphology of adipocytes. Immunohistochemistry (IHC), fluorescent immunohistochemistry (FIHC), and Western blotting (WB) were performed to detect protein expression levels.
The chemical constituents of DHHL medicinal materials were identified and analyzed using UPLC-MS/MS. Total ion chromatograms (TIC) were acquired in both positive and negative ion modes. Pie charts were generated to illustrate the abundance distribution and quantitative proportion of different components. HFD feeding induced significant increases in body weight and FBG in rats, elevated serum triglycerides (TG) and free fatty acids (FFA) levels, and promoted hypertrophy and hyperplasia of adipose tissue, while also disrupting glucose metabolism. DHHL treatment significantly improved body weight, FBG, glucose uptake capacity, and insulin sensitivity in obese rats. It also reduced blood lipid levels and lipid accumulation in a dose-dependent manner. Transcriptomic sequencing revealed that the anti-obesity effects of DHHL were closely associated with the upregulation of thermogenesis-related gene expression. KEGG pathway enrichment analysis indicated that DHHL may exert regulatory effects through pathways such as AMPK, PPAR, and PI3K. TEM observations demonstrated that DHHL increased mitochondrial numbers within adipocytes of obese rats. Molecular analyses further showed that DHHL upregulated the expression of thermogenesis-associated proteins-including PPARγ, PRDM16, and UCP1-thereby promoting the browning of white adipose tissue (WAT). Moreover, DHHL enhanced the expression levels of AMPK, SIRT1, and PGC-1α.
DHHL effectively ameliorates HFD-induced obesity in rats, and its therapeutic mechanism is closely associated with the activation of the AMPK/SIRT1/PGC-1α signaling pathway, which promotes the browning of WAT.
大黄（）-黄连（）（DHHL）已被证明能有效治疗饮食不规律引起的肥胖。然而，导致这种现象的基本过程尚未阐明。
采用超高效液相色谱-串联质谱法（UPLC-MS/MS）分析DHHL的化学成分。通过高脂饮食（HFD）诱导建立大鼠肥胖模型并进行相应验证。给肥胖大鼠灌胃不同剂量的DHHL。检测并记录每组大鼠的代谢指标。采用转录组分析评估DHHL对肥胖大鼠基因表达的影响。用苏木精-伊红（H&E）染色和透射电子显微镜（TEM）观察脂肪细胞形态。进行免疫组织化学（IHC）、荧光免疫组织化学（FIHC）和蛋白质免疫印迹法（WB）检测蛋白质表达水平。
采用UPLC-MS/MS对DHHL药材的化学成分进行了鉴定和分析。在正离子和负离子模式下均获得了总离子色谱图（TIC）。生成饼状图以说明不同成分的丰度分布和定量比例。高脂饮食喂养导致大鼠体重和空腹血糖（FBG）显著增加，血清甘油三酯（TG）和游离脂肪酸（FFA）水平升高，促进脂肪组织肥大和增生，同时也扰乱了葡萄糖代谢。DHHL治疗显著改善了肥胖大鼠的体重、空腹血糖、葡萄糖摄取能力和胰岛素敏感性。它还以剂量依赖的方式降低血脂水平和脂质积累。转录组测序显示，DHHL的抗肥胖作用与产热相关基因表达的上调密切相关。KEGG通路富集分析表明，DHHL可能通过AMPK、PPAR和PI3K等通路发挥调节作用。TEM观察表明，DHHL增加了肥胖大鼠脂肪细胞内的线粒体数量。分子分析进一步表明，DHHL上调了产热相关蛋白（包括PPARγ、PRDM16和UCP1）的表达，从而促进白色脂肪组织（WAT）的褐色化。此外，DHHL提高了AMPK、SIRT1和PGC-1α的表达水平。
DHHL能有效改善高脂饮食诱导的大鼠肥胖，其治疗机制与激活AMPK/SIRT1/PGC-1α信号通路密切相关，该通路促进白色脂肪组织的褐色化。
