Synthesis, anti-aging and mechanism of magnolol derivatives

Xinxin Pang; Li Mao; Danyang Ye; Wenqi Wang; Hongliu Yang; Xiaoxiao Fan; Yuping Yang; Zhijun Su; Tao Ma; Mingqian Sun; Yonggang Liu

doi:10.3389/fchem.2023.1180375

Synthesis, anti-aging and mechanism of magnolol derivatives

Front Chem. 2023 May 23:11:1180375. doi: 10.3389/fchem.2023.1180375. eCollection 2023.

Authors

Xinxin Pang¹, Li Mao², Danyang Ye¹, Wenqi Wang¹, Hongliu Yang¹, Xiaoxiao Fan¹, Yuping Yang¹, Zhijun Su¹, Tao Ma¹, Mingqian Sun³, Yonggang Liu¹

Affiliations

¹ School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
² Beijing Tide Pharmaceutical Co, Ltd., Beijing Econnomi Technological Development Area (BDA), Beijing, China.
³ Institute of Basic Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Abstract

Magnolol (M), a hydroquinone containing an allyl side chain, is one of the major active components of Houpoea officinalis for antioxidation and anti-aging. To enhance the antioxidant activity of magnolol, the different sites of magnolol were structurally modified in this experiment, and a total of 12 magnolol derivatives were obtained. Based on the preliminary exploration of the anti-aging effect of magnolol derivatives in a Caenorhabditis elegans (C. elegans) model. Our results indicate that the active groups of magnolol exerting anti-aging effects were allyl groups and hydroxyl on the phenyl. Meanwhile, the anti-aging effect of the novel magnolol derivative M27 was found to be significantly superior to that of magnolol. To investigate the effect of M27 on senescence and the potential mechanism of action, we investigated the effect of M27 on senescence in C. elegans. In this study, we investigated the effect of M27 on C. elegans physiology by examining body length, body curvature and pharyngeal pumping frequency. The effect of M27 on stress resistance in C. elegans was explored by acute stress experiments. The mechanism of M27 anti-aging was investigated by measuring ROS content, DAF-16 nuclear translocation, sod-3 expression, and lifespan of transgenic nematodes. Our results indicate that M27 prolonged the lifespan of C. elegans. Meanwhile, M27 improved the healthy lifespan of C. elegans by improving pharyngeal pumping ability and reducing lipofuscin accumulation in C. elegans. M27 increased resistance to high temperature and oxidative stress in C. elegans by reducing ROS. M27 induced DAF-16 translocation from cytoplasm to nucleus in transgenic TJ356 nematodes and upregulated the expression of sod-3 (a gene downstream of DAF-16) in CF1553 nematodes. Furthermore, M27 did not extend the lifespan of daf-16, age-1, daf-2, and hsp-16.2 mutants. This work suggests that M27 may ameliorate aging and extend lifespan in C. elegans through the IIS pathway.

Keywords: Caenorhabditis elegans; lifespan; magnolol; magnolol derivatives; stress resistant.

Grants and funding

National Natural Science Foundation of China (grant nos. 82130113); Fundamental Research Funds for the Central Universities (grant nos. 2020-JYB-ZDGG-040).