Ikeda Rie, Yanagisawa Masayoshi, Takahashi Nobuyuki, Kawada Teruo, Kumazawa Shigenori, Yamaotsu Noriyuki, Nakagome Izumi, Hirono Shuichi, Tsuda Takanori
College of Bioscience and Biotechnology, Chubu University, Kasugai, Aichi 487-8501, Japan.
Biochim Biophys Acta. 2011 Jul;1810(7):695-703. doi: 10.1016/j.bbagen.2011.04.007. Epub 2011 Apr 29.
Previous reports suggest that Brazilian propolis has multiple biological functions and may help to restore adiponectin expression and insulin sensitivity. However, little is known about the molecular mechanisms by which these compounds inhibit the downregulation of adiponectin.
The effect of various Brazilian propolis-derived components on inhibition of tumor necrosis factor-α (TNF-α)-mediated downregulation of adiponectin expression in 3T3-L1 adipocytes and molecular mechanism was investigated.
Pretreatment with either artepillin C (C3) or its derivative (C4) significantly inhibited TNF-α-mediated downregulation of adiponectin expression in 3T3-L1 adipocytes. Interestingly, C3 strongly activated peroxisome proliferator-activated receptor γ (PPARγ) transcriptional activity. Treatment of adipocytes with C3 resulted in the upregulation of adiponectin and fatty acid-binding protein 4 expression, but C4 did not significantly induce PPARγ transactivation. C4 did, however, inhibit the TNF-α-induced c-Jun-NH(2)-terminal kinase (JNK) signaling that is involved in adiponectin expression. Molecular docking studies based on hPPARγ with C3 and JNK1 with C4 clearly supported our experimental results. These data demonstrate that 1) both C3 and C4 significantly inhibit the TNF-α-mediated downregulation of adiponectin in adipocytes, 2) C3 functions as a PPARγ agonist, and its inhibition of the effect of TNF-α is due to this PPARγ transactivation, and 3) C4 is an effective inhibitor of JNK activation, thus inhibiting the TNF-α-mediated downregulation of adiponectin.
Brazilian propolis-derived components (C3 and C4) can significantly inhibit TNF-α-mediated downregulation of adiponectin in adipocytes, although they do so via different mechanisms.
先前的报道表明，巴西蜂胶具有多种生物学功能，可能有助于恢复脂联素表达和胰岛素敏感性。然而，关于这些化合物抑制脂联素下调的分子机制知之甚少。
研究了各种巴西蜂胶衍生成分对肿瘤坏死因子-α（TNF-α）介导的3T3-L1脂肪细胞中脂联素表达下调的抑制作用及其分子机制。
用artepillin C（C3）或其衍生物（C4）预处理可显著抑制TNF-α介导的3T3-L1脂肪细胞中脂联素表达的下调。有趣的是，C3强烈激活过氧化物酶体增殖物激活受体γ（PPARγ）的转录活性。用C3处理脂肪细胞导致脂联素和脂肪酸结合蛋白4表达上调，但C4未显著诱导PPARγ反式激活。然而，C4确实抑制了参与脂联素表达的TNF-α诱导的c-Jun-NH(2)-末端激酶（JNK）信号传导。基于hPPARγ与C3以及JNK1与C4的分子对接研究明确支持了我们的实验结果。这些数据表明：1）C3和C4均显著抑制脂肪细胞中TNF-α介导的脂联素下调；2）C3作为PPARγ激动剂发挥作用，其对TNF-α作用的抑制归因于这种PPARγ反式激活；3）C4是JNK激活的有效抑制剂，从而抑制TNF-α介导的脂联素下调。
巴西蜂胶衍生成分（C3和C4）可显著抑制脂肪细胞中TNF-α介导的脂联素下调，尽管它们通过不同机制发挥作用。
