5′-Hydroxy-6, 7, 8, 3′, 4′-pentamethoxyflavone (5-HPF), a polymethoxyflavone compound found in dikamali gum, has been shown to exert a range of beneficial effects on health. We have previously reported that 5-HPF improves the cholinergic dysfunction and also possesses antioxidant properties in Caenorhabditis elegans. In this study, we have identified the effect of 5-HPF on the worm lifespan and its underlying molecular mechanisms. Out of the five tested pharmacological doses of 5-HPF, viz. 6.25, 12.5, 25, 50, and 100 μM, the 50 μM dose maximally extended the mean life of C. elegans by 28%. The present study revealed that 5-HPF supplementation leads to dietary restriction (DR)-like effects in the worms without altering bacterial metabolism. The analysis of mutant animals fed with 5-HPF suggested that the extended lifespan of C. elegans depends upon multiple DR-related signaling pathways, with NRF2 and FOXA being critical factors. Further investigation into the mechanistic aspects indicated that 5-HPF utilizes autophagy pathway induced by DR through the upregulation of autophagy genes bec-1 and lgg-1, evident from the increase in autophagic puncta in the seam cells of lgg-1::gfp tagged worms. This study identifies the longevity-promoting activity of 5-HPF in C. elegans regulated by oxidative stress-resistance genes and DR-induced autophagy pathway.

5'-羟基-6,7,8,3',4'-五甲氧基黄酮 (5-HPF) 是一种在迪卡马利口香糖中发现的多甲氧基黄酮化合物，已被证明对健康具有一系列有益作用。我们之前曾报道过，5-HPF 可以改善秀丽隐杆线虫的胆碱能功能障碍，并具有抗氧化特性。在这项研究中，我们确定了 5-HPF 对线虫寿命的影响及其潜在的分子机制。在 5-HPF 的五个测试药理学剂量中，即。6.25、12.5、25、50 和 100 μM，50 μM 剂量最大可将线虫的平均寿命延长28%。本研究表明，补充 5-HPF 会对线虫产生类似饮食限制 (DR) 的作用，但不会改变细菌代谢。对喂食 5-HPF 的突变动物的分析表明，线虫寿命的延长取决于多种 DR 相关信号通路，其中 NRF2 和 FOXA 是关键因素。对机制方面的进一步研究表明，5-HPF 通过上调自噬基因bec-1和lgg-1来利用 DR 诱导的自噬途径，从lgg-1 :: gfp标记的接缝细胞中自噬点的增加可以明显看出蠕虫。本研究确定了 5-HPF 在秀丽隐杆线虫中的长寿活性，该活性受氧化应激抗性基因和 DR 诱导的自噬途径的调节。