L-Quebrachitol from Sea Buckthorn Leaves Extends Lifespan by Regulating Antioxidant Activity and Autophagy through AMP-Activated Protein Kinase/SIR-2.1/DAF-16 and IIS Signaling Pathways

L-Quebrachitol (QBC), a derivative of L-inositol, exhibits antioxidant and antimetabolic disorder properties; however, its antiaging effects remain unexplored. This study isolated QBC from sea buckthorn leaves using the CaO/resin purification-methanol precipitation method. The structure was confirmed using nuclear magnetic resonance (NMR), X-ray diffraction (XRD), ultraperformance liquid chromatography-mass spectrometry (UPLC-MS), and fourier transform infrared spectroscopy (FTIR). QBC was found to extend the lifespan of Caenorhabditis elegans (with an optimal dose of 50 μg/mL), reduce lipofuscin accumulation, and enhance stress resistance, motility, and mitochondrial health. Further studies have found that QBC activates the AMP-activated protein kinase (AMPK) signaling pathway via dietary restriction and mitochondrial uncoupling. This then upregulates the key transcription factors DAF-16, SKN-1, and HSF-1 within the SIR-2.1 and Insulin/insulin-like growth factor signaling (IIS) pathways. The activation of these transcription factors helps to maintain protein homeostasis and enhances nematode resistance. In addition, QBC demonstrated significant Autophagy induction, dependent on the regulation of AMPK and DAF-16. In conclusion, this study provides the first insight into the antiaging activity of QBC and its potential mechanisms. By activating the AMPK/SIR-2.1/DAF-16 and IIS signaling pathways, QBC regulates the antioxidant system and the Autophagy response, thereby effectively delaying the aging process in C. elegans.

AMP-activated protein kinase; Caenorhabditis elegans; L-quebrachitol; insulin/insulin-like growth factor signaling; lifespan; mitochondrial autophagy.