Calenduloside E\nAmeliorates Inflammatory Responses\nin Adipose Tissue via Sirtuin 2‑NLRP3 Inflammasome Axis

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