Skeletal muscle is a major tissue of glucose consumption and plays an important role in glucose homeostasis. Prenylflavonoids, a component of Macaranga tanarius fruits, have been reported to have antioxidant, antibacterial, and anticancer effects. However, the effects of these compounds on skeletal muscle glucose metabolism are unclear. Here, we isolated five prenylflavonoids from M. tanarius fruits, and investigated the mechanism of action of these compounds on skeletal muscle cells using L6 myotubes. We found that isonymphaeol B and 3′-geranyl naringenin increased glucose uptake in a dose-dependent manner. Furthermore, both isonymphaeol B and 3′-geranyl naringenin increased AMPK phosphorylation but did not affect PI3K-Akt phosphorylation. Isonymphaeol B and 3′-geranyl naringenin also increased Glut1 mRNA expression and plasma membrane GLUT1 protein levels. These results suggest that isonymphaeol B and 3′-geranyl naringenin have beneficial effects on glucose metabolism through AMPK and GLUT1 pathway. Isonymphaeol B and 3′-geranyl naringenin may be potential lead candidates for antidiabetic drug development.

Graphical abstract

中文翻译：

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猕猴桃果实中的异戊二烯类黄酮通过 L6 肌管中的 AMPK 激活促进葡萄糖摄取

骨骼肌是葡萄糖消耗的主要组织，在葡萄糖稳态中起着重要作用。异戊二烯类黄酮是Macaranga tanarius果实的一种成分，据报道具有抗氧化、抗菌和抗癌作用。然而，这些化合物对骨骼肌葡萄糖代谢的影响尚不清楚。在这里，我们从M. tanarius 中分离出了五种异戊二烯类黄酮水果，并使用 L6 肌管研究了这些化合物对骨骼肌细胞的作用机制。我们发现异香酚 B 和 3'-香叶基柚皮素以剂量依赖性方式增加葡萄糖摄取。此外，异香酚 B 和 3'-香叶基柚皮素均增加了 AMPK 磷酸化，但不影响 PI3K-Akt 磷酸化。异香酚 B 和 3'-香叶基柚皮素还增加了Glut1 mRNA 表达和质膜 GLUT1 蛋白水平。这些结果表明异香酚 B 和 3'-香叶基柚皮素通过 AMPK 和 GLUT1 途径对葡萄糖代谢具有有益作用。Isonymphaeol B 和 3'-香叶基柚皮素可能是抗糖尿病药物开发的潜在先导候选物。

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