The efficacy and mechanisms of Maiguanfukang Tablets, a patented herbal-based TCM formula, for the treatment of atherosclerosis: An in vivo experiment based on the network pharmacology.

Abstract

Objective: To investigate the efficacy and potential mechanisms of MGFKP on rabbit atherosclerotic models.

Methods: The left carotid balloon injury surgery were used to establish the rabbit atherosclerotic model, followed by the administration of MGFKP from the second postoperative for 6 weeks. Left carotid ultrasound and histological analysis were determined to evaluate the anti-atherosclerotic efficacy of MGFKP. Additionally, LC-MS and network pharmacology were conducted to identify the active ingredients of MGFKP and their targets, respectively. Lastly, core targets were selected to validate using immunohistochemical staining, western blot or ELISA.

Results: The results revealed that the vascular diameters difference, plaque area, plaque thickness, and ratio of vessel lumen to vessel cross-section radius were significantly improved following treatment with MGFKP (P<0.05). 539 ingredients of MGFKP were identified by LC-MS, and 23 ingredients were screened using SwissADME for network pharmacology. After combining the results of PPI and KEGG analyses with published literature, TLR4, NF-κB, IL-1β, and TNF-α were selected for the ensuing analyses. Molecular docking of most compounds showed satisfactory docking energy between TLR4, NF-κB, IL-1β, and TNF-α with their matched compounds. Finally, immunohistochemical analysis of TLR4 and western blot results of NF-κB, TNF-α, and IL-1β demonstrated that these proteins levels were obviously increased in the model group and significantly decreased in MGFKP group (P<0.05). The levels of TNF-α, IL-6, IL-1β were also significantly reduced following MGFKP treatment.

Conclusions: MGFKP was a potential drug for the treatment of atherosclerosis, and might suppress the TLR4/NF-κB inflammatory pathway to alleviate atherosclerotic plaque progression.