Obesity-related metabolic diseases are associated with a chronic inflammatory state. Calenduloside E (CE) is a triterpene saponin from sugar beet. In mouse models, CE reduced pro-inflammatory cytokines in white adipose tissue (WAT) and decreased macrophage infiltration of WAT. And CE inhibited pyroptosis in J774A.1 cells and WAT by inhibiting the activation of the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome. Moreover, CE could trigger the activation of Sirtuin 2 (SIRT2), leading to a decrease in the acetylation of NLRP3, particularly at the K24 site. In addition, it has been shown that CE can reduce inflammation in adipocytes that have been induced by macrophage-conditioned medium. However, the selective SIRT2 inhibitor AGK2 hindered the beneficial effects of CE. In summary, CE has the capacity to impede NLRP3-mediated pyroptosis by triggering SIRT2 activity, thus positioning CE as a promising therapeutic avenue for combating obesity-related metabolic disorders.

中文翻译：

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金盏花苷 E 通过 Sirtuin 2-NLRP3 炎症小体轴改善脂肪组织的炎症反应


肥胖相关的代谢疾病与慢性炎症状态有关。 Calenduloside E (CE) 是一种来自甜菜的三萜皂苷。在小鼠模型中，CE 减少了白色脂肪组织 (WAT) 中的促炎细胞因子，并减少了 WAT 的巨噬细胞浸润。 CE通过抑制核苷酸结合寡聚化结构域、富含亮氨酸重复序列和含pyrin结构域3 (NLRP3)炎性体的激活来抑制J774A.1细胞和WAT中的细胞焦亡。此外，CE 可以触发 Sirtuin 2 (SIRT2) 的激活，导致 NLRP3 的乙酰化减少，特别是在 K24 位点。此外，研究表明，CE 可以减少巨噬细胞条件培养基诱导的脂肪细胞炎症。然而，选择性 SIRT2 抑制剂 AGK2 阻碍了 CE 的有益作用。总之，CE 能够通过触发 SIRT2 活性来阻止 NLRP3 介导的细胞焦亡，从而将 CE 定位为对抗肥胖相关代谢紊乱的有前景的治疗途径。