School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Biogerontology. 2024 Oct 29;26(1):2. doi: 10.1007/s10522-024-10142-6.
Isotschimgine (ITG) is a bornane-type monoterpenoid derivative naturally occurring in genus Ferula plants and propolis. Its effects on aging and the underlying mechanisms are not yet well understood. This study employed Caenorhabditis elegans (C. elegans) as a model organism to evaluate the potential of ITG in extending lifespan, enhancing healthspan, and promoting neuroprotection, while exploring the underlying mechanisms involved. The results showed that ITG extended the lifespan and healthspan of C. elegans, significantly enhanced stress resistance and detoxification functions. Studies on mutants and qPCR data indicated that ITG-mediated lifespan extension was modulated by the insulin/IGF-1 signaling pathway and nuclear hormone receptors. Furthermore, ITG markedly increased stress-responsive genes, including daf-16 and its downstream genes sod-3 and hsp-16.2, as well as NHR downstream detoxification-related genes cyp35a1, cyp35b3, cyp35c1, gst-4, pgp-3 and pgp-13. Additionally, ITG alleviated β-amyloid-induced paralysis and behavioral dysfunction in transgenic C. elegans strains. The neuroprotective efficacy of ITG was weakened by RNAi knockdown of nuclear hormone receptors daf-12 and nhr-8. Overall, our study identifies ITG as a potential compound for promoting longevity and neuroprotection, mediated through nuclear hormone receptors.
异土木香内酯（ITG）是一种天然存在于阿魏属植物和蜂胶中的土沉香型单萜衍生物。其对衰老的影响及其潜在机制尚不清楚。本研究采用秀丽隐杆线虫（C. elegans）作为模型生物，评估 ITG 延长寿命、增强健康寿命和促进神经保护的潜力，并探讨其中涉及的潜在机制。结果表明，ITG 延长了 C. elegans 的寿命和健康寿命，显著增强了应激抗性和解毒功能。对突变体和 qPCR 数据的研究表明，ITG 介导的寿命延长受胰岛素/IGF-1 信号通路和核激素受体的调节。此外，ITG 显著增加了应激响应基因，包括 daf-16 及其下游基因 sod-3 和 hsp-16.2，以及 NHR 下游解毒相关基因 cyp35a1、cyp35b3、cyp35c1、gst-4、pgp-3 和 pgp-13。此外，ITG 减轻了β-淀粉样蛋白诱导的转染 C. elegans 品系的瘫痪和行为功能障碍。核激素受体 daf-12 和 nhr-8 的 RNAi 敲低削弱了 ITG 的神经保护功效。总的来说，我们的研究确定 ITG 是一种具有促进长寿和神经保护作用的潜在化合物，其作用机制涉及核激素受体。
