Zhu Shidian, Liu Yanlin, Bu Wenyu, Liu Yanzi, Chen Wandi, Liu Fuming
Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, China.
The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Heliyon. 2024 Sep 18;10(19):e37957. doi: 10.1016/j.heliyon.2024.e37957. eCollection 2024 Oct 15.
Naoluotong granules (NLTGs) are a medicinal formula derived from traditional Chinese medicine, which have been demonstrated to be effective in slowing down the progression of atherosclerosis (AS) through clinical practice and animal experiments. By means of multidimensional analysis, the relevant mechanism of NLTGs in delaying the progression of atherosclerosis was studied, which is conducive to its widespread adoption.
In this study, data from network pharmacology and GEO database were comprehensively analysed to identify differentially expressed core cluster genes (DECCGs). Subsequently, multilevel analyses were applied to investigate the potential mechanistic linkages and causal associations of NLTGs in delaying atherosclerosis.
Eight DECCGs positively correlated with atherosclerosis risk were identified, with (Huangjing), (Shuizhi), and (Chuanxiong) as the core drug pairs. Senkyunone, Wallichilide, and Aurantiamide were the core components. The prediction model using principal components (PC) demonstrated high accuracy and clinical relevance. The mechanisms were strongly associated with the PI3K-Akt signaling pathway, as well as the polarization of Macrophages M0 and the balanced regulation of M1/M2 types. Ultimately, elevated expression of CTSB was causally associated with increased risk of cerebral atherosclerosis (OR = 1.313; 95 % CI = 1.024-1.685; = 0.032).
Employing multidimensional analysis, we identified core pairs, components, and targets of NLTGs. Our multilevel analysis of DECCGs enabled the construction of a clinical prediction model, highlighting CTSB as a risk target for AS. Additionally, we unveiled NLTGs' mechanisms closely tied to the polarization and regulation of macrophage, facilitating subsequent research and application.
脑络通颗粒是一种源自中药的方剂，通过临床实践和动物实验已证明其在减缓动脉粥样硬化（AS）进展方面有效。通过多维度分析，研究了脑络通颗粒延缓动脉粥样硬化进展的相关机制，这有利于其广泛应用。
本研究综合分析了网络药理学数据和基因表达综合数据库（GEO）的数据，以识别差异表达的核心聚类基因（DECCGs）。随后，应用多层次分析来研究脑络通颗粒在延缓动脉粥样硬化方面的潜在机制联系和因果关联。
确定了8个与动脉粥样硬化风险呈正相关的DECCGs，其中黄精、水蛭和川芎为核心药对。洋川芎内酯、千里光裂碱和橙酰胺为核心成分。使用主成分（PC）的预测模型显示出高准确性和临床相关性。其机制与PI3K-Akt信号通路以及巨噬细胞M0的极化和M1/M2类型的平衡调节密切相关。最终，组织蛋白酶B（CTSB）表达升高与脑动脉粥样硬化风险增加存在因果关联（OR = 1.313；95%CI = 1.024 - 1.685；P = 0.032）。
通过多维度分析，我们确定了脑络通颗粒的核心药对、成分和靶点。我们对DECCGs的多层次分析构建了一个临床预测模型，突出了CTSB作为动脉粥样硬化的风险靶点。此外，我们揭示了脑络通颗粒的机制与巨噬细胞的极化和调节密切相关，有助于后续的研究和应用。
