Gypenoside LXXV Alleviates Colitis by Reprograming Macrophage Polarization via the Glucocorticoid Receptor Pathway,Journal of Agricultural and Food Chemistry

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Gypenoside LXXV Alleviates Colitis by Reprograming Macrophage Polarization via the Glucocorticoid Receptor Pathway
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-09-09 , DOI: 10.1021/acs.jafc.4c04784
Wenjing Wu ₁ , Xian Qu ₁ , Chenxing Hu ₁ , Xuepeng Zhu ₁ , Mengqi Wan ₁ , Yifa Zhou ₁ , Hairong Cheng ₁

Affiliation

An imbalance in the macrophage phenotype is closely related to various inflammatory diseases. Here, we discovered that gypenoside LXXV (GP-75), a type of saponin from Gynostemma pentaphyllum, can reprogram M1-like macrophages into M2-like ones. On a mechanistic level, GP-75 inhibits NF-κB-COX2 signaling by targeting the glucocorticoid receptor (GR). Administration of GP-75, either orally or by intraperitoneal injection, significantly alleviates ulcerative colitis in mice, a pathogenesis associated with macrophage polarization. Clodronate liposomes, which deplete macrophages in mice, as well as GR antagonist RU486, abrogate the anticolitis effect of GP-75, thus confirming the pivotal role of macrophages in GP-75 function. We also showed that GP-75 has no toxicity in mice. Overall, this is the first report that demonstrates the effect of GP-75 on macrophage reprograming and as an agent against colitis. Because G. pentaphyllum is gaining popularity as a functional food, our findings offer new perspectives on the use of gypenosides as potential nutraceuticals for medical purposes.

中文翻译：

绞股蓝皂苷 LXXV 通过糖皮质激素受体途径重新编程巨噬细胞极化来减轻结肠炎

巨噬细胞表型失衡与多种炎症性疾病密切相关。在这里，我们发现绞股蓝皂苷 LXXV (GP-75) 是一种来自绞股蓝的皂苷，可以将 M1 样巨噬细胞重编程为 M2 样巨噬细胞。在机制水平上，GP-75 通过靶向糖皮质激素受体 (GR) 来抑制 NF-κB-COX2 信号传导。口服或腹腔注射 GP-75 可显着缓解小鼠溃疡性结肠炎，这是一种与巨噬细胞极化相关的发病机制。消除小鼠巨噬细胞的氯膦酸盐脂质体以及 GR 拮抗剂 RU486 消除了 GP-75 的抗结肠炎作用，从而证实了巨噬细胞在 GP-75 功能中的关键作用。我们还表明 GP-75 对小鼠没有毒性。总的来说，这是第一份证明 GP-75 对巨噬细胞重编程的影响以及作为抗结肠炎药物的报告。由于五叶绞股蓝作为一种功能性食品越来越受欢迎，我们的研究结果为绞股蓝皂苷作为潜在的医疗保健营养品的使用提供了新的视角。

更新日期：2024-09-09

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