Pang Xinxin, Mao Li, Ye Danyang, Wang Wenqi, Yang Hongliu, Fan Xiaoxiao, Yang Yuping, Su Zhijun, Ma Tao, Sun Mingqian, Liu Yonggang
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
Beijing Tide Pharmaceutical Co, Ltd., Beijing Econnomi Technological Development Area (BDA), Beijing, China.
Front Chem. 2023 May 23;11:1180375. doi: 10.3389/fchem.2023.1180375. eCollection 2023.
Magnolol (M), a hydroquinone containing an allyl side chain, is one of the major active components of 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 () 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 . In this study, we investigated the effect of M27 on physiology by examining body length, body curvature and pharyngeal pumping frequency. The effect of M27 on stress resistance in 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 . Meanwhile, M27 improved the healthy lifespan of by improving pharyngeal pumping ability and reducing lipofuscin accumulation in . M27 increased resistance to high temperature and oxidative stress in 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 through the IIS pathway.
厚朴酚（M）是一种含有烯丙基侧链的对苯二酚，是具有抗氧化和抗衰老作用的主要活性成分之一。为增强厚朴酚的抗氧化活性，本实验对厚朴酚的不同位点进行了结构修饰，共获得12种厚朴酚衍生物。基于在秀丽隐杆线虫（Caenorhabditis elegans）模型中对厚朴酚衍生物抗衰老作用的初步探索。我们的结果表明，厚朴酚发挥抗衰老作用的活性基团是烯丙基和苯环上的羟基。同时，发现新型厚朴酚衍生物M27的抗衰老作用明显优于厚朴酚。为研究M27对衰老的影响及其潜在作用机制，我们研究了M27对秀丽隐杆线虫衰老的影响。在本研究中，我们通过检测体长、身体弯曲度和咽部抽动频率来研究M27对秀丽隐杆线虫生理学的影响。通过急性应激实验探索M27对秀丽隐杆线虫抗应激能力的影响。通过测量活性氧（ROS）含量、DAF-16核转位、sod-3表达以及转基因线虫的寿命来研究M27抗衰老的机制。我们的结果表明，M27延长了秀丽隐杆线虫的寿命。同时，M27通过改善咽部抽动能力和减少秀丽隐杆线虫体内脂褐素积累来提高其健康寿命。M27通过减少ROS来增加秀丽隐杆线虫对高温和氧化应激的抵抗力。M27在转基因TJ356线虫中诱导DAF-16从细胞质转位到细胞核，并在CF1553线虫中上调sod-3（DAF-16下游的一个基因）的表达。此外，M27没有延长daf-16、age-1、daf-2和hsp-16.2突变体的寿命。这项工作表明，M27可能通过胰岛素/胰岛素样生长因子信号（IIS）通路改善秀丽隐杆线虫的衰老并延长其寿命。
