The upregulation of adiponectin production has been suggested as a novel strategy for the treatment of metabolic diseases. Galangin, a natural flavonoid, exhibited adiponectin synthesis-promoting activity during adipogenesis in human bone marrow mesenchymal stem cells. In target identification, galangin bound both peroxisome proliferator-activated receptor (PPAR) γ and estrogen receptor (ER) β. Novel galangin derivatives were synthesized to improve adiponectin synthesis-promoting compounds by increasing the PPARγ activity of galangin and reducing its ERβ activity, because PPARγ functions can be inhibited by ERβ. Three galangin 3-benzyl-5-methylether derivatives significantly promoted adiponectin production by 2.88-, 4.47-, and 2.76-fold, respectively, compared to the effect of galangin. The most potent compound, galangin 3-benzyl-5,7-dimethylether, selectively bound to PPARγ (Ki, 1.7 μM), whereas it did not bind to ERβ. Galangin 3-benzyl-5,7-dimethylether was identified as a PPARγ partial agonist in docking and pharmacological competition studies, suggesting that it may have diverse therapeutic potential in a variety of metabolic diseases.

已提出脂联素产生的上调作为治疗代谢疾病的新策略。高良姜素是一种天然类黄酮，在人骨髓间充质干细胞的脂肪形成过程中表现出促进脂联素合成的活性。在目标识别中，高良姜素结合过氧化物酶体增殖物激活受体 (PPAR) γ 和雌激素受体 (ER) β。合成了新的高良姜素衍生物，通过增加高良姜素的 PPARγ 活性和降低其 ERβ 活性来改善脂联素合成促进化合物，因为 PPARγ 功能可以被 ERβ 抑制。与高良姜素的作用相比，三种高良姜素 3-苄基-5-甲基醚衍生物分别显着促进脂联素的产生 2.88 倍、4.47 倍和 2.76 倍。最有效的化合物，高良姜素 3-benzyl-5,7-dimethylether，Ki , 1.7 μM)，而它不与 ERβ 结合。高良姜素 3-benzyl-5,7-dimethylether 在对接和药理竞争研究中被确定为 PPARγ 部分激动剂，表明它可能在多种代谢疾病中具有多种治疗潜力。