An in vitro investigation of the effects of Urolithins A and B on low-density lipoprotein uptake and its regulatory genes

Introduction - Material and methods The possible role of Urolithin A (UA) and Urolithin B (UB) on the induction of LDL uptake and the expression of its regulatory genes was eexplored using HepG2 cells and curcumin (20 uM), berberine (50 uM), UA (80 uM), and UB (80 uM) as the treatments in the experimental tests. Results The LDL uptake as well as cell-surface LDLR were higher in cells treated with UA in compari-son with cells treated with UB, and even in relation to the cells treated with curcumin and ber-berine as positive controls. In addition, cells treated with UB showed approximately 2 times greater LDLR expression levels compared with curcumin (FC: 2.144, P=0.013) and berberine (FC: 2.761, P=0.006). However, UA treatment resulted in significantly lower expression levels of LDLR compared with curcumin (FC: 0.274, P<0.001) and berberine (FC: 0.352, P=0.009). UB demonstrated approximately 8 times greater LDLR expression levels when compared with UA (FC:7.835, P=0.001). Compared with UB, as well as curcumin and berberine as positive controls, UA was more efficient in reducing PCSK9 expression levels. Although UB did not show any significant differences compared with curcumin and berberine, it illustrated higher levels of PCSK9 expression when compared with the UA group (FC: 3.694, P<0.001). Conclusions The present results support that UA was more effective than UB in promoting LDL uptake as well as cell surface LDLR in HepG2 cells. This effect seems to be mostly mediated through the sup-pression of PCSK9 expression but not the induction of LDLR expression.