Caffeic acid phenethyl ester (CAPE), extracted from propolis, was evaluated for the ameliorative effects on insulin resistance and the mechanisms were identified, using non-insulin-dependent diabetes mellitus (NIDDM) model mice and insulin resistance (IR) model cells. After 5 weeks of CAPE supplementation, insulin sensitivity, hyperlipidemia, and peroxisome proliferator-activated receptor-α (PPAR-α) levels were improved in mice. Proinflammatory cytokines in serum and the expressions of tumor necrosis factor-alpha (TNF-α) mRNA in tissues were markedly downregulated from CAPE-treated mice. In vitro, CAPE supplement significantly improved glucose consumption, glucose uptake, glycogen content, and oxidative stress and decreased expression of glucose-6-phosphatase (G6Pase) mRNA in cells. Both in vivo and in vitro, CAPE enhanced p-Akt (Ser473) and p-insulin receptor substrate (IRS)-1 (Tyr612), but inhibited p-JNK (Thr183/Tyr185), p-NF-κB p65 (Ser536), and nuclear translocation of p-NF-κB p65 (Ser536). In summary, CAPE can ameliorate insulin resistance through modulation of JNK and NF-κB signaling pathway in mice and HepG2 cells.

中文翻译：

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咖啡酸苯乙基酯（蜂胶提取物）通过抑制糖尿病小鼠和HepG2细胞模型中的JNK和NF-κB炎症途径改善胰岛素抵抗。

评估了从蜂胶中提取的咖啡酸苯乙酯（CAPE）对胰岛素抵抗的改善作用，并使用非胰岛素依赖性糖尿病（NIDDM）模型小鼠和胰岛素抵抗（IR）模型细胞鉴定了其机制。补充CAPE 5周后，小鼠的胰岛素敏感性，高脂血症和过氧化物酶体增殖物激活的受体-α（PPAR-α）水平得到改善。CAPE处理的小鼠血清中的促炎细胞因子和组织中肿瘤坏死因子-α（TNF-α）mRNA的表达明显下调。在体外，CAPE补充剂可显着改善葡萄糖消耗，葡萄糖摄取，糖原含量和氧化应激，并降低细胞中葡萄糖6磷酸酶（G6Pase）mRNA的表达。无论是体内还是体外，CAPE增强了p-Akt（Ser473）和p-胰岛素受体底物（IRS）-1（Tyr612），但抑制了p-JNK（Thr183 / Tyr185），p-NF-κBp65（Ser536）和p-核的核易位NF-κBp65（Ser536）。总之，CAPE可以通过调节小鼠和HepG2细胞中的JNK和NF-κB信号通路来改善胰岛素抵抗。