Combining Experimental Validation and Network Pharmacology to Reveal the Action Mechanism of Panax Notoginseng-Radix Salviae on Atherosclerosis

Abstract

Ningning Song,1,2 Xinrong Zhang,3 Honglin Yin,3 Lei Zhang,1 Chao Li,4 Jian Li,5 Yunlun Li,4,* Jibiao Wu1,* 1College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 2Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 3First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 4Department of Cardiovascular, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 5Department of Medical Imaging, The Fifth People’s Hospital of Jinan City, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jibiao Wu, College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, People’s Republic of China, Tel [phone], Email [email protected] Yunlun Li, Department of Cardiovascular, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of China, Tel [phone], Email [email protected]: Few studies have evaluated the mechanisms of the specific efficacy of Panax notoginseng-Radix Salviae couplet medicines (PN-RS) in the treatment of atherosclerosis (AS). This study aims to explore the potential bioactive ingredients and molecular mechanisms of PN-RS in the treatment of AS.Materials and Methods: C57BL/6J mice were fed a common diet as the control group. ApoE−/− mice were randomly divided into the model, PN-RS treatment (0.75 mgPN+3.75 mgRS/g/day via gavage), and positive drug groups (rosuvastatin, 1.25 mg/kg/day via gavage). After two months of drugs intervention, H&E and Masson staining, the serum lipid concentration and atherosclerotic index were conducted to verify the PN-RS efficacy. Network pharmacology analysis was carried out to identify the pathways and targets of PN-RS. The signaling pathway-related targets and cytokines were tested via enzyme-linked immunosorbent assay (ELISA), Western blotting and real-time polymerase chain reaction (PCR).Results: Network pharmacology analysis identified the JAK2-STAT3 signaling pathway as a key pathway through which PN-RS exerts its therapeutic effects. Results from animal experiments demonstrated that PN-RS significantly reduced the atherosclerotic lesion area and decreased serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and atherogenic index (AI). Mechanistic studies further revealed that PN-RS inhibited the JAK2-STAT3 signaling pathway and reduced the concentrations of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein-1 (MCP-1).Conclusion: These findings suggest that PN-RS could be a promising treatment for atherosclerosis, applicable across diverse populations. Future research should investigate its efficacy in various demographic groups and in combination with other therapies.Keywords: traditional Chinese medicine, atherosclerosis, lipid metabolism, inflammatory reaction, network pharmacology

Keywords

• traditional chinese medicine
• atherosclerosis
• lipid metabolism
• inflammatory reaction
• network pharmacology