Tanshinone IIA alleviate atherosclerosis and hepatic steatosis via down-regulation of MAPKs/NF-κB signaling pathway.

Objectives: Tanshinone IIA (Tan IIA) exhibits therapeutic potential for atherosclerosis (AS) and hepatic steatosis (HS). The study aims to explore the mechanisms underlying the anti-atherosclerosis and anti-hepatic steatosis effects of Tan IIA.

Methods: The LDLRmice were divided into control, model, low/high Tan IIA and atorvastatin group, which fed with High-fat diet to build NAFLD-associated AS model, then administrated with 0.9 % saline, Tan IIA or atorvastatin. RAW264.7 cells divided into control, LPS, LPS plus low/high Tan IIA and LPS plus Tan IIA plus JNK activator group. The different goups' pathological changes visualized with H&E, Oil Red O and Immunofluorescence staining. The therapeutic effect of Tan IIA was reflected by lipids metabolism changes, hepatic indexes, inflammation levels. ELISA, RT-qPCR and Western blot assay were used to determine the inflammatory factors and upstream proteins. Molecular docking was used to reconfirm the importance of genes studied and locate the specific gene will study.

Results: Tan IIA alleviated LDLRmice AS and HS by reducing AS plaque area, lowering serum &liver lipid levels (TC, TG), improving liver function (AST, ALT). Tan IIA decreased serum inflammation levels (IL-1β, IL-6, TNF-α) and aorta & liver inflammatory-related cytokines levels (iNOS, VCAM-1, IL-6) and inhibited the phosphorylation of aorta & liver protein ERK1/2, JNK, p38 and NF-κB p65, which were validated in the LPS-stimulated macrophages supernatant and cells.

Conclusions: The study indicated that Tan IIA can alleviate atherosclerosis and hepatic steatosis via down-regulating MAPKs/NF-κB signaling pathway. This provides a potential therapeutic strategy for the co-existing situation of atherosclerosis and hepatic steatosis.