Synthesis of Novel Pinocembrin Amino Acid Derivatives and Their Antiaging Effect on Caenorhabditis elegans via the Modulating DAF-16/FOXO

Abstract

Pinocembrin is a dihydroflavonoid, which is widely found in several plant species. Although pinocembrin has good pharmacological activity, it has poor water solubility and low bioavailability. Therefore, we have modified the structure of pinocembrin with a combination of different amino acids to solve this problem. Moreover, the effect of the antiaging activity of them has not been explored. We aim to investigate the effect of pinocembrin and its amino acid derivatives on the aging of Caenorhabditis elegans. Methods: Pinocembrin was spliced with different amino acids in order to obtain their corresponding derivatives. The preliminary research of pinocembrin and its amino acid derivatives on antiaging effect was studied by using the C. elegans model. Among all the compounds, the one shows the best antiaging effect was then studied on antiaging mechanism. The protective effect on nematodes under emergency conditions was explained by detecting the ROS content and sod-3p::GFP fusion protein expression in nematodes; the possible anti-aging mechanism of nematodes was determined by DAF-16 nuclear localization experiment and the survival curve of transgenic nematodes model under stress conditions. Results: Pb-3 showed the best effect on increasing tolerance to thermal and oxidative stress and reduce the accumulation of lipofuscin. In the assay of C. elegans, pb-3 reduced intracellular ROS accumulation. Application of pb-3 to the transgenic mutant TJ356 induced the translocation of the transcription factor DAF-16 from the cytosol to the nucleus, and modulated the expression of SOD-3 (downstream genes of daf-16), which regulates longevity in C. elegans. Moreover, pb-3 did not prolong the lifespan of daf-16, age-1, daf-2 and hsp16.2 mutants, suggesting that these genetic pathways are involved in mediating the antiaging effects of pb-3. Conclusion:The antioxidant and antiaging properties of pb-3 may involve in the DAF-16/ FOXO transcription process. Pinocembrin amino acid derivatives might be a novel agent for antiaging therapy.

Glycerol and Antimicrobial Peptide-Modified Natural Latex for Bacteriostasis of Skin Wounds

“…It may be due to the addition of GI that makes the NRL-GI and NRL-GI-AMP films non-resistant to high temperature and easy to age . In addition, the AMP in the NRL-GI-AMP film is a protein with a short-chain structure and has an antiaging effect, so the heat resistance of the NRL-GI-AMP film is higher than that of the NRL-GI film . Zhan et al reported that the addition of soy protein to natural rubber can promote the construction of a vulcanization network, increase the rigidity of the rubber, and reduce the breakage of the rubber chain.…”

Hylocereus undatus extends lifespan and exerts neuroprotection in Caenorhabditis elegans via DAF-16 mediated pathway

“…7). The nuclear localization of DAF-16 is very crucial in the activation of anti-aging, stress resistance and neuroprotection [78][79][80]. Multiple pathways including mitogen activated protein kinase pathway and mammalian target of rapamycin aids in the nuclear localization of DAF-16, thereby activating DAF-16 and induce longevity [81].…”

Ellagic Acid Increases Stress Resistance via Insulin/IGF-1 Signaling Pathway in Caenorhabditis elegans

“…DAF-16 is an important transcription factor related to the longevity and stress response in C. elegans [ 35 , 36 , 37 ]. Under normal conditions, DAF-16 is located in the cytoplasm but translocated to the nucleus to activate a series of genes and proteins involved in the stress response pathways to resist unfavorable factors under harmful conditions [ 23 , 38 ].…”