Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, 443002, China; College of Basic Medical Science, China Three Gorges University, Yichang, 443002, China.
Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, 443002, China; College of Medicine and Health Science, China Three Gorges University, Yichang, 443002, China.
Phytomedicine. 2023 Jul;115:154827. doi: 10.1016/j.phymed.2023.154827. Epub 2023 Apr 21.
The rising incidence of metabolic diseases due to chronic inflammation in the adipose tissue has been attributed to factors such as high fat diet (HFD). Previous studies have demonstrated that the total saponins from Panax japonicus (TSPJ) can reduce HFD-induced adipocyte inflammation, but the underlying mechanism remains unclear. In this work, we explored the molecular mechanism by which TSPJ reduces inflammation response in adipocytes.
We first established C57BL/6 mouse and 3T3-L1 adipocyte models. Lentiviruses packaged with the plasmids were injected into mice through the tail vein or into adipocytes to generate the in vivo and in vitro models with miR155 knockdown and overexpression. The mice were fed with HFD to trigger inflammation and administered TSPJ (25 mg/kg∙d and 75 mg/kg∙d) by gavage. The adipocytes were treated with palmitic acid (PA) to trigger inflammation response, then treated with TSPJ (25 μg/ml and 50 μg/ml). Finally, the expression of miR155, inflammatory factors, SOCS1, and NFκB pathway-related proteins was explored.
TSPJ significantly inhibited the expression of inflammation-related genes and the miR155 expression in adipocytes both in vitro and in vivo. The dual luciferase reporter gene assay revealed that miR155 mediated the downregulation of SOCS1. TSPJ significantly inhibited and upregulated the phosphorylation of the NFκB protein and the SOCS1 proteins, respectively.
TSPJ inhibits miR155 to upregulate the SOCS1 expression, which subsequently inhibits the NFκB signaling pathway, thereby mitigating the inflammatory response in the adipocytes of HFD mice.
脂肪组织慢性炎症导致代谢性疾病发病率上升，这与高脂肪饮食（HFD）等因素有关。先前的研究表明，人参总皂苷（TSPJ）可以减少 HFD 诱导的脂肪细胞炎症，但具体机制尚不清楚。在这项工作中，我们探讨了 TSPJ 降低脂肪细胞炎症反应的分子机制。
首先建立 C57BL/6 小鼠和 3T3-L1 脂肪细胞模型。通过尾静脉或向脂肪细胞注射包装有质粒的慢病毒，分别构建体内和体外 miR155 敲低和过表达模型。用 HFD 喂养小鼠以引发炎症，并通过灌胃给予 TSPJ（25mg/kg·d 和 75mg/kg·d）。用棕榈酸（PA）处理脂肪细胞以引发炎症反应，然后用 TSPJ（25μg/ml 和 50μg/ml）处理。最后，探讨了 miR155、炎症因子、SOCS1 和 NFκB 通路相关蛋白的表达。
TSPJ 显著抑制了体外和体内脂肪细胞中炎症相关基因和 miR155 的表达。双荧光素酶报告基因检测显示，miR155 介导了 SOCS1 的下调。TSPJ 显著抑制和上调了 NFκB 蛋白和 SOCS1 蛋白的磷酸化。
TSPJ 通过抑制 miR155 来上调 SOCS1 的表达，从而抑制 NFκB 信号通路，减轻 HFD 小鼠脂肪细胞的炎症反应。
