State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
National Engineering Research Center for Marine Aquaculture, Institute of Innovation & Application, Zhejiang Ocean University, Zhoushan, China.
Food Funct. 2022 Nov 14;13(22):11853-11864. doi: 10.1039/d2fo01450e.
Adipose tissue inflammation is believed to be the most important contributor to obesity associated insulin resistance and related metabolic diseases. Pogostone (PO) is a major component of the essential oil from (Blanco) Benth., which is used as a natural additive for food flavoring. Herein, we explored the therapeutic effects and the underlying mechanisms of PO against adipose tissue inflammation. In TNF-α-induced differentiated adipocytes, PO downregulated the phosphorylation of MAPKs and the NF-κB pathway by triggering the SIRT1 activation. , PO suppressed the migratory ability of macrophages to inflammatory adipocytes and reduced inflammatory cytokine and chemokine expression in macrophages stimulated by conditioned media from differentiated adipocytes. Notably, the above effects are attributed to blocking of the MAPK and NF-κB signal activation by hampering the SIRT1 expression, as pre-treatment with an inhibitor of SIRT1-Ex527 on adipocytes abolished the anti-inflammatory effects of PO. Furthermore, PO mitigated the levels and expressions of inflammatory cytokines in the serum and epididymal adipose tissue of LPS induced mice, as well as increased the level of the anti-inflammatory cytokine IL-10 and observably inhibited the cytokine and chemokine expression in adipose tissue. PO suppressed the phosphorylation of MAPK and NF-κB signals and promoted the SIRT1 expression in adipose tissue. In summary, our results demonstrate that PO ameliorates adipose tissue inflammation through activating SIRT1, which modulates the inflammatory pathway comprising MAPK and NF-κB signals and drives the beneficial reciprocal interactions between adipocytes and macrophages. Thus, our study suggests that PO may be a bioactive constituent for treatment of obesity and related metabolic diseases by targeting adipose tissue inflammation.
脂肪组织炎症被认为是与肥胖相关的胰岛素抵抗和相关代谢疾病的最重要诱因。莪术酮（PO）是（Blanco）Benth. 挥发油的主要成分，可用作天然食品调味添加剂。本研究旨在探索 PO 对脂肪组织炎症的治疗作用及其机制。在 TNF-α诱导分化的脂肪细胞中，PO 通过触发 SIRT1 激活来下调 MAPK 和 NF-κB 通路的磷酸化。此外，PO 抑制了巨噬细胞向炎症性脂肪细胞的迁移能力，并减少了由分化脂肪细胞条件培养基刺激的巨噬细胞中炎性细胞因子和趋化因子的表达。值得注意的是，上述作用归因于通过阻碍 SIRT1 表达来阻断 MAPK 和 NF-κB 信号的激活，因为用 SIRT1 抑制剂 Ex527 预处理脂肪细胞可消除 PO 的抗炎作用。此外，PO 减轻了 LPS 诱导的小鼠血清和附睾脂肪组织中炎性细胞因子的水平和表达，并增加了抗炎细胞因子 IL-10 的水平，明显抑制了脂肪组织中细胞因子和趋化因子的表达。PO 抑制了 MAPK 和 NF-κB 信号的磷酸化，并促进了脂肪组织中 SIRT1 的表达。综上所述，我们的研究结果表明，PO 通过激活 SIRT1 来改善脂肪组织炎症，从而调节包含 MAPK 和 NF-κB 信号的炎症通路，并促进脂肪细胞和巨噬细胞之间的有益相互作用。因此，我们的研究表明，PO 可能是通过靶向脂肪组织炎症来治疗肥胖和相关代谢疾病的生物活性成分。
