State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science and Technology (TUST), Tianjin 300457, China.
Department of Agriculture, Hetao College, Inner Mongolia Bayannur, China.
Comp Biochem Physiol C Toxicol Pharmacol. 2023 Dec;274:109755. doi: 10.1016/j.cbpc.2023.109755. Epub 2023 Sep 20.
D-pinitol (DP) has been extensively regarded as the main active component of legumes for anti-aging. In this study, we intended to explore the anti-aging mechanism of DP, utilizing computer modeling techniques. The results demonstrated that DP significantly delayed HO-induced cellular senescence. Model PC12 cells treated with DP exhibited increased cell viability, increased antioxidant enzyme activity (SOD, CAT), and reduced ROS and MDA levels. Furthermore, DP was discovered to have a positive effect on healthy longevity. In C. elegans, DP treatment enhanced lifespan, stress capacity, antioxidant capacity (T-SOD/CAT/GSH-Px/MDA/ROS), and altered aging-related indicators of lipofuscin accumulation, pharyngeal pump rate, motility, and reproduction. Moreover, DP could reduce the toxicity Aβ in transgenic C. elegans CL4176, CL2355, and CL2331. Further mechanistic studies indicated DP increased transcription factor (daf-16, skn-1, hsf-1) expression of insulin/insulin-like growth factor-1 signaling (IIS) pathway. As expected, DP also extended the downstream target genes of the three transcription factors (sod-3, ctl-1, ctl-2, gst-4, hsp-16.1, and hsp-16.2). Further mutant lifespan experiments, network pharmacology, and molecular docking revealed that DP might be life-extending through the IIS pathway. DP deserves extensive investigation and development as a potential anti-aging drug in the future.
D-松醇（DP）一直被广泛认为是豆类植物抗衰老的主要活性成分。在这项研究中，我们拟利用计算机建模技术探索 DP 的抗衰老机制。结果表明，DP 能显著延缓 HO 诱导的细胞衰老。用 DP 处理的模型 PC12 细胞表现出更高的细胞活力、更高的抗氧化酶活性（SOD、CAT）以及更低的 ROS 和 MDA 水平。此外，DP 被发现对健康长寿有积极作用。在秀丽隐杆线虫中，DP 处理能延长寿命、提高应激能力、增强抗氧化能力（T-SOD/CAT/GSH-Px/MDA/ROS）并改变脂褐素积累、咽泵率、运动和繁殖等与衰老相关的指标。此外，DP 能减少转基线虫 CL4176、CL2355 和 CL2331 中 Aβ 的毒性。进一步的机制研究表明 DP 能增加胰岛素/胰岛素样生长因子-1 信号通路（IIS）的转录因子（daf-16、skn-1、hsf-1）表达。正如预期的那样，DP 还能延长这三个转录因子的下游靶基因（sod-3、ctl-1、ctl-2、gst-4、hsp-16.1 和 hsp-16.2）的表达。进一步的突变体寿命实验、网络药理学和分子对接表明 DP 可能通过 IIS 通路延长寿命。DP 值得进一步研究和开发，有望成为未来的一种潜在抗衰老药物。
