State Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou, 570228, China.
Adv Sci (Weinh). 2024 Sep;11(36):e2401862. doi: 10.1002/advs.202401862. Epub 2024 Jul 29.
The pursuit of pharmacological interventions in aging aims focuses on maximizing safety and efficacy, prompting an exploration of natural products endowed with inherent medicinal properties. Subsequently, this work establishes a unique library of plant extracts sourced from Yunnan Province, China. Screening of this herbal library herein revealed that Salsola collina (JM10001) notably enhances both lifespan and healthspan in C. elegans. Further analysis via network pharmacology indicates that the p53 signaling pathway plays a crucial role in mediating the anti-aging effects of JM10001. Additionally, this work identifies that a composition, designated as JM10101 and comprising three chemical constituents of JM10001, preserves the original lifespan-extending activity in C. elegans. Both JM10001 and JM10101 mitigate aging symptoms in senescence-accelerated mice treated with doxorubicin and in naturally aged mice. Notably, JM10101 exhibits a more sophisticated senomorphlytic role encompassing both senomorphic and senolytic functions than JM10001 in the modulation of senescent cells, offering a promising strategy for the discovery of combination drugs in the rational development of anti-aging therapies.
衰老相关的药物干预研究旨在实现安全性和有效性的最大化，因此人们开始探索具有内在药用特性的天然产物。随后，本研究建立了一个独特的植物提取物文库，这些提取物均来自中国云南省。本研究中的草本文库筛选发现，山莨菪（JM10001）可明显延长秀丽隐杆线虫的寿命并改善其健康状况。通过网络药理学进一步分析表明，p53 信号通路在介导 JM10001 的抗衰老作用中发挥关键作用。此外，本研究还发现一种名为 JM10101 的成分，它由 JM10001 的三种化学成分配制而成，保留了其在秀丽隐杆线虫中延长寿命的原始活性。JM10001 和 JM10101 均可减轻阿霉素处理的加速衰老小鼠和自然衰老小鼠的衰老症状。值得注意的是，JM10101 在调节衰老细胞方面表现出更复杂的衰老表型溶胞作用，兼具衰老表型和衰老溶胞功能，相较于 JM10001，它为发现组合药物提供了一种有前景的策略，有助于合理开发抗衰老疗法。
