Inhibition of microsomal triglyceride transfer protein expression and atherogenic risk factor apolipoprotein B100 secretion by tanshinone IIA in HepG2 cells

Salvia miltiorrhiza Bunge is known to be effective for the treatment of cardiovascular diseases. Here, we have isolated tanshinone IIA (T-IIA) from S. miltiorrhiza Bunge. The aim of this study is to address the mechanisms where apolipoprotein B-100 (ApoB) regulation is associated with T-IIA, since T-IIA regulates the lipoprotein metabolism in liver cells. Human HepG2 cells treated with T-IIA for 24 h exerted a dose-dependent inhibitory effect on ApoB secretion together with triglyceride. However, another secretory protein, albumin, was unaffected by T-IIA treatment, indicating that the effect of T-IIA is specific for ApoB secretion. T-IIA decreased the transcription level of microsomal triglyceride transfer protein gene, suggesting that lipoprotein assembly is likely to be involved in the inhibited ApoB secretion. Interestingly, T-IIA inhibited ApoB secretion via a proteasome-dependent pathway. Our results suggest that T-IIA is an influential inhibitor of ApoB secretion and triglyceride secretion in liver cells.