Potential mechanistic linkages of Naoluotong granules on the remission of atherosclerosis by multidimensional analysis

Background: 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.

Materials and methods: 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.

Results: Eight DECCGs positively correlated with atherosclerosis risk were identified, with Polygonatum sibiricum (Huangjing), Hirudo nipponica (Shuizhi), and Ligusticum chuanxiong (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; P = 0.032).

Conclusions: 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.