The Thorn Formononetin Raised The Reverse Cholesterol Transport Pathway Key Protein In SR-BI And ABCA1 And Anti Artery Atherosclerosis Effect

Epidemic evidences shows that the high level of plasma high density lipoprotein cholesterol is closed to low risk of coronary heart disease.Moderating the plasma level of HDL-C has become an important therapy target for anti-atherosclerosis.Recent studies revealed that the antiatherosclerotic effect of HDL was mainly attributed to its role in reverse cholesterol transport(RCT).Scavenger receptor class B typeⅠ(SR-BI) and the ATP-binding cassette transporter A1(ABCA1) are tow significant proteins in RCT pathway,which control the metabolism of HDL in vivo.SR-BI is HDL receptor;ABCA1 moderates the rate-controlling step in the HDL particle formation.Therefore,identification of novel up-regulators of SR-BI and ABCA1 would be beneficial for atherosclerosis prevention and/or therapy due to its pivotal role in cholesterol homeostasis and HDL metabolism.Based on our previous established cell-based high-throughput screening(HTS) assay for SR-BI upregulator and assay for ABCA1 up-regulator,we found that formononetin (7-Hydroxy -4'-methoxy isoflavone) a novel isoflavone compound activatied their transcription.And the up-regulating effect of formononetin on CLA-1/hSR-BI and ABCA1 were induced by its PPARγagonistic activity.It was then confirmed that formononetin enhanced the transcriptions of CLA-1/hSR-BI and ABCA1 by quantitative RT-PCR and increased their translations by flow-cytometer in HepG2 cells.Formononetin inhibited raw 264.7 cells(mouse monocyte-macrophage) converting to foam cells.Formononetin influenced the plasma levels of HDL-C,TC,LDL-C,TG on hyperlipidemic hamsters in a time-dependent manner.It played a positive role in adjusting lipid and lipoprotein metabolism in vivo.Furthermore formononetin increased hepatic expression of CLA-1/hSR-BI and ABCA1.To some extent,formononetin reverses pathological states of hepatic lipogenesis,prevent developmental process of atherosclerosis in arota wall. Therefore,it may become a potential drug candidates or lead compound for anti-atherosclerosis through new therapy targets.