Daxing Research Institute, University of Science and Technology Beijing, Beijing 100083, China.
School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China.
Comb Chem High Throughput Screen. 2024;27(12):1840-1849. doi: 10.2174/0113862073276253231114063813.
Traditional Chinese Medicine (TCM) has a rich history of use in preventing senescence for millennia in China. Nonetheless, a systematic method to study the antiaging properties and the underlying molecular mechanism of TCM remains absent.
The objective of this study is to decipher the anti-aging targets and mechanisms of Sisheng Bulao Elixir (SBE) using a systematic approach based on a novel aging database and network pharmacology.
Bioactive compounds and target proteins in SBE were identified via the Traditional Chinese Medicine System Pharmacology (TCMSP) database. Aging-related proteins were uncovered through alignment with the Ageing Alta database. A compound-target (CT) protein network analysis highlighted key flavonoids targeting aging. Core aging-related proteins were extracted through protein-protein interaction (PPI) network analysis. Molecular docking validated binding activities between core compounds and aging-related proteins. The antioxidant activity of SBE was confirmed using an senescent cells model.
A total of 39 active compounds were extracted from a pool of 639 compounds in SBE. Through a matching process with the Aging Alta, 88 target proteins associated with the aging process were identified. Impressively, 80 out of these 88 proteins were found to be targeted by flavonoids. Subsequently, an analysis using CT methodology highlighted 11 top bioactive flavonoids. Notably, core aging-related proteins, including AKT1, MAPK3, TP53, VEGFA, IL6, and HSP90AA1, emerged through the PPI network analysis. Moreover, three flavonoids, namely quercetin, kaempferol, and luteolin, exhibited interactions with over 100 aging-related proteins. Molecular docking studies were conducted on these flavonoids with their shared three target proteins, namely AKT1, HSP90AA1, and IL6, to assess their binding activities. Finally, the antioxidant properties of SBE were validated using an in vitro model of senescent cells.
This study offers novel insights into SBE's anti-aging attributes, providing evidence of its molecular mechanisms. It enhances our understanding of traditional remedies in anti-aging research.
中医药在中国已有几千年的历史，用于预防衰老。然而，缺乏一种系统的方法来研究中医药的抗衰老特性和潜在的分子机制。
本研究旨在采用基于新型衰老数据库和网络药理学的系统方法，解析四物汤抗衰老的靶点和机制。
通过中药系统药理学（TCMSP）数据库鉴定四物汤中的生物活性化合物和靶蛋白。通过与 Ageing Alta 数据库比对，发现与衰老相关的蛋白质。通过化合物-靶标（CT）蛋白网络分析，突出针对衰老的关键黄酮类化合物。通过蛋白质-蛋白质相互作用（PPI）网络分析提取核心衰老相关蛋白。分子对接验证核心化合物与衰老相关蛋白之间的结合活性。使用衰老细胞模型验证四物汤的抗氧化活性。
从四物汤的 639 种化合物中提取了 39 种活性化合物。通过与 Aging Alta 匹配过程，确定了 88 种与衰老过程相关的靶蛋白。令人印象深刻的是，这 88 种蛋白质中有 80 种被黄酮类化合物靶向。随后，通过 CT 方法分析，突出了 11 种顶级生物活性黄酮类化合物。值得注意的是，通过 PPI 网络分析，出现了核心衰老相关蛋白，包括 AKT1、MAPK3、TP53、VEGFA、IL6 和 HSP90AA1。此外，三种黄酮类化合物，即槲皮素、山奈酚和木樨草素，与 100 多种衰老相关蛋白相互作用。对这些黄酮类化合物及其共享的三个靶蛋白（AKT1、HSP90AA1 和 IL6）进行分子对接研究，以评估它们的结合活性。最后，使用衰老细胞的体外模型验证了四物汤的抗氧化特性。
本研究为四物汤的抗衰老特性提供了新的见解，为其分子机制提供了证据。它增强了我们对传统药物在抗衰老研究中的认识。
