Author + information
Tanshinone IIA (Tan IIA), a lipophilic constituent of Salvia miltiorrhiza Bunge, has shown a promising cardioprotective effect including anti-atherosclerosis (anti-AS). This study aims to investigate whether Tan IIA could play anti-inflammatory and immune-regulating roles in stabilizing vulnerable atherosclerotic plaque in apoE deficient mice via Toll-like receptor 4 (TLR4)/myeloid differentiation factor88 (MyD88)/nuclear factor-kappa B (NF-κB) signaling pathway.
Male apoE deficient (ApoE-/-) mice were fed with a high fat diet for 12 weeks and then randomized to vehicle (MOD) or Tan IIA (high dose (HT): 90 mg/kg/day, moderate dose (MT): 30 mg/kg/day, low dose (LT): 10 mg/kg/day) or atorvastatin (ATO) (5mg/kg/day) for 13 weeks. Male C57BL/6 mice were fed with normal chow diet as control. The plaque stability was evaluated according to the morphology and composition of atherosclerotic plaque in HE staining and Movat staining sections by calculating the area proportion of extracellular lipid, collagenous fiber and foam cells to the plaque. The expression of key genes of TLR4/MyD88/NF-κB signaling pathway in aorta fractions was determined by immunohistochemistry and real-time polymerase chain reaction (RT-PCR). The concentrations of tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) were detected by cytometric bead array.
Tan IIA stabilized aortic plaque with a striking reduction in the area proportion of extracellular lipid (ATO: 13.15±1.2%, HT: 12.2±1.64%, MT: 13.93±1.59%, MOD: 18.84±1.46%, P<0.05) or foam cells (ATO: 16.05±1.26%, HT: 14.88±1.79%, MT: 16.61±1.47%, MOD: 22.08±1.69%, P<0.05) to the plaque, and an evident increase in content of collagenous fiber (ATO: 16.22±1.91%, HT: 17.58±1.33%, MT: 15.71±2.26%, LT: 14.92±1.65%, MOD: 9.61±0.7%, P<0.05) to the plaque than that in the model group, concomitant with down-regulation the protein expression of TLR4, MyD88 and NF-κB p65, serum level of MCP-1, TNF-α and mRNA of TLR4, MyD88 and intercellular cell adhesion molecule-1 (ICAM-1) in a dose-dependent manner.
These results suggest Tan IIA could stabilize vulnerable AS plaque in ApoE-/- mice via TLR4/MyD88/NF-κB signaling pathway, which might be a potential candidate agent with anti-inflammatory and immune-regulating effect in the prevention and treatment of AS.