Qu Zhai ¹ Shixi Shang ² Zihan Zhang ³ Lihua Sun ² Ying Huang ² Shuyi Feng ² Qian Wu ² Haifeng Cui ² Shi Xiaolu ^2*

• ¹ China National Medical Products Administration Institute of Executive Development, Beijing, China
• ² Experimental Research Center, China Academy of Chinese Medical Science, Beijing, China
• ³ Beijing University of Chinese Medicine, Beijing, Beijing Municipality, China

Background: This study employs Network pharmacology and molecular docking methods in conjunction with animal experimentation to elucidate the underlying mechanism by which the combination of Salvianolic phenolic acids and Hawthorn triterpenic acids (SHC) exerts its therapeutic effect on carotid atherosclerosis in ApoE-/- mice. Methods: Using Network pharmacology research approach to predict potential core targets for SHC intervention in atherosclerosis. The predictions were subsequently validated through the implementation of animal in vivo experiments. ApoE-/- mice were randomly assigned to three experimental groups: a Model group, an Atorvastatin group,and a SHC group.Following the conclusion of the administration period, the plaque area of the carotid artery and aortic arch,blood lipids levels, MDA, SOD, GSH, and NO content were measured. Additionally, the expression of PI3K, Akt, NF-κB, JNK1, ERK1/2, and p38-MAPK in the aortic arteries was analyzed. Based on the protein expression results, the binding activity was predicted through molecular docking between the core compounds and core targets. Results: A total of 23 core compounds were identified in SHC and 55 core targets of SHC were screened as potential targets for intervention in AS.The results of the enrichment analysis indicated that the principal mechanisms through which SHC exerts its effects in AS are associated with lipid metabolism and the PI3K-Akt and MAPK pathways. The results of animal experimental demonstrated that Atorvastatin and SHC were capable of markedly reducing the area of carotid plaque and downregulating the levels of TC and LDL-C in ApoE-/- mice.The administration of SHC was associated with an increase in SOD activity and a reduction in NO levels in the livers of mice. Furthermore, SHC was observed downregulated the expression of NF-κB and p38-MAPK in the carotid region.The results of the Molecular docking demonstrated that the core compounds of SHC, including Salvianolic acid A, B, C, Maslinic, Ursolic, and Oleic acids were capable of stably binding to the core targets NF-κB and MAPK14. Conclusion:It is hypothesized that SHC may reduce lipid deposition and plaque formation in AS by regulating blood lipids, a process that may be closely linked to the inhibition of inflammatory regulator expression, including NF-κB and p38-MAPK.