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Hypercholesterolemia is a major risk factor for cardiovascular disease. Mulberry leaf (ML) is a Traditional Chinese Medicine used to treat hyperlipidemia in clinical settings. The aim of the present study was to identify the potential effect and possible target of ML in anti-hypercholesterolemia. Male Sprague-Dawley rats were fed with a high-fat diet and treated with ML for 5 weeks. Blood lipid levels, total cholesterol (TC) and total bile acid (TBA) in the liver and feces were measured to assess the effects of ML on hypercholesterolemia. Harris's hematoxylin staining and oil red O staining was applied to observe the pathological change and lipid accumulation in the liver. Immunohistochemical assay was performed to observe the location of expressions of scavenger receptor class B type I and low-density lipoprotein (LDL) receptor (-R), and western blotting was applied to determine the protein expression of ATP-binding cassette transporter G5/G8 (ABCG5/8), nuclear transcription factor peroxisome proliferator-activated receptor-α (PPARα), farnesoid-X receptor (FXR) and cholesterol 7α-hydroxylase 1 (CYP7A1). The results demonstrated that ML treatment reduced serum TC and LDL-cholesterol levels, and liver TC and TBA contents; increased serum HDL-C levels, and fecal TC and TBA contents; and alleviated hepatocyte lipid degeneration. In addition, ML treatment inhibited liver LDL-R, PPARα and FXR protein expression, promoted protein expression of CYP7A1, and maintained the ratio of ABCG5/ABCG8. The findings of the present study provide a positive role of ML on cholesterol clearance via promoting cholesterol and TBA execration via FXR- and CYP7A1-mediated pathways; RCT regulation may be a potential mechanism of ML on anti-hypercholesterolemia.
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