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

PURPOSE: 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.