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新型匹诺西布林氨基酸衍生物的合成及其通过调节 DAF-16/FOXO 对秀丽隐杆线虫的抗衰老作用

 

Authors Wang W, Feng X, Du Y, Liu C, Pang X, Jiang K, Wang X, Liu Y

Received 23 July 2021

Accepted for publication 11 September 2021

Published 5 October 2021 Volume 2021:15 Pages 4177—4193

DOI https://doi.org/10.2147/DDDT.S330223

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Anastasios Lymperopoulos

Purpose: 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.
Keywords: pinocembrin, antiaging, oxidative stress, amino acid derivatives, Caenorhabditis elegans , DAF-16/FOXO transcription factors