The present study demonstrates that T9 inhibits in vitro the 3-hydroxy-3-methylglutaryl CoA reductase (HMGCoAR) functionality with an IC50 value of 99.5 ± 0.56 μM. Through the inhibition of either HMGCoAR or PCSK9 (D374Y) activities, T9 enhances the low-density lipoprotein receptor (LDLR) protein levels leading to an improved ability of HepG2 cells transfected with the mutant PCSK9 (D374Y)-FLAG plasmid to uptake extracellular low-density lipoprotein (LDL) with a final cholesterol-lowering effect. In addition, T9 modulates the PCSK9 (D374Y) signaling pathway in transfected HepG2 cells leading to a decrease of PCSK9(D374Y) and HNF-1 alpha protein levels.
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