This study aims to elucidate the mechanism by which allicin modulates lipid metabolism in HFD (High-Fat Diet) mice through the CSE/H2S pathway. Allicin intervention (120 mg/kg) significantly reduced mouse body weight and serum total cholesterol (TC) and triglyceride (TG) levels (p < 0.05), while enhancing hepatic antioxidant levels (p < 0.05). Transcriptomic analysis of the liver indicated that allicin influenced several key metabolic pathways, including lipid metabolism (steroid hormone synthesis, unsaturated fatty acid synthesis, and PPAR signaling pathways) and antioxidant pathways (chemical carcinogenesis-reactive oxygen species pathway and glutathione metabolism pathways). RT-qPCR experiments confirmed that in the HA group (the high dose allicin, 120 mg/kg), the expression level of CD36 in the liver was downregulated, while the expression of LPL, GST, GPX, and GCLC were upregulated. Furthermore, the metabonomic analysis identified core differential metabolites primarily associated with sulfate/sulfite metabolism and glutathione metabolism pathway. This was evidenced by alterations in the levels of sulfur-containing compounds, such as H2S, l-Glutathione (reduced), G-glutamylcysteine, and methionine. In the constructed HepG2 high-fat cell model, dl-Propargylglycine (PAG, H2S synthesis inhibitor) treatment resulted in significantly higher lipid content compared to the Allicin-600 group, and expression levels of antioxidant genes like GST, GPX, and GCLC are reduced. This further validates the pivotal role of the CSE/H2S pathway in allicin's lipid-lowering effects. In summary, allicin demonstrates potent lipid-lowering activity when serving as an H2S donor, setting the stage for the development of a broader range of allicin-related health products.

中文翻译：

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基于 CSE/H2S 通路的探索大蒜素降血脂机制


本研究旨在阐明大蒜素通过 CSE/H2S 通路调节 HFD（高脂饮食）小鼠脂质代谢的机制。大蒜素干预 （120 mg/kg） 显着降低小鼠体重和血清总胆固醇 （TC） 和甘油三酯 （TG） 水平 （p < 0.05），同时提高肝脏抗氧化水平 （p < 0.05）。肝脏转录组学分析表明，大蒜素影响几个关键的代谢途径，包括脂质代谢 （类固醇合成、不饱和脂肪酸合成和 PPAR 信号通路） 和抗氧化途径 （化学致癌-活性氧途径和谷胱甘肽代谢途径）。RT-qPCR 实验证实，HA 组 （大蒜素高剂量，120 mg/kg） 肝脏中 CD36 的表达水平下调，而 LPL 、 GST 、 GPX 和 GCLC 的表达上调。此外，代谢组学分析确定了主要与硫酸盐/亚硫酸盐代谢和谷胱甘肽代谢途径相关的核心差异代谢物。含硫化合物水平的变化证明了这一点，例如 H2S、l-谷胱甘肽（还原）、G-谷氨酰半胱氨酸和蛋氨酸。在构建的 HepG2 高脂肪细胞模型中，dl-炔丙基甘氨酸 （PAG， H2S 合成抑制剂） 处理导致脂质含量与大蒜素 600 组相比显著升高，并且 GST 、 GPX 和 GCLC 等抗氧化基因的表达水平降低。这进一步验证了 CSE/H2S 通路在大蒜素降脂作用中的关键作用。总之，大蒜素在作为 H2S 供体时表现出强大的降脂活性，为开发更广泛的大蒜素相关健康产品奠定了基础。