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Cellular cholesterol levels are controlled by several transcription factors, including sterol-regulatory element-binding proteins (SREBPs). SREBP cleavage-activating protein (SCAP) acts as a cholesterol sensor responsible for regulating cellular cholesterol balance. We built an in vitro detection system to explore the SCAP–SREBP pathway inhibitory activities of Traditional Chinese Medicine (TCMs). Firstly, a bipartite graph composed of human disease and TCMs linked by medicine-disease binary associations was built. A subnetwork that contained about 100 kinds of medicines concerned with lipid metabolism was identified. Then a stable HepG2 cell line coupled to the firefly luciferase reporter gene was established to evaluate the SREBP pathway inhibitory activities of these medicines. Furthermore, the effects of synthesizing of endogenous cholesterol were investigated using reverse transcription polymerase chain reaction (RT-PCR) assay and amphotericin B cell model. Results revealed that crude extracts of Rhizoma Alismatis and Semen Cassiae showed favorable efforts on inhibiting the activities of SREBP pathway and the biosynthesis of cholesterol. Taken together, Rhizoma Alismatis and Semen Cassiae may be potential source of lipid-lowing drugs in the further drug discovery.

An in vitro test system for evaluation of SCAP–SREBP pathway inhibitory activities of Traditional Chinese Medicines