Effects of mulberry leaf on experimental hyperlipidemia rats induced by high-fat diet - PubMed (original) (raw)
Effects of mulberry leaf on experimental hyperlipidemia rats induced by high-fat diet
Jianbo Huang et al. Exp Ther Med. 2018 Aug.
Abstract
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.
Keywords: bile acid; cholesterol 7α-hydroxylase 1; hyperlipidemias; reverse cholesterol transport.
Figures
Figure 1.
Effects of ML on serum lipid levels and fecal TC and TBA levels in high-fat diet-fed rats. (A) Serum TC levels; (B) serum TG levels; (C) serum LDL-C levels; (D) serum HDL-C levels; (E) fecal TC levels; (F) fecal TBA levels. Data are presented as the mean ± standard error of the mean (n=8). ∆P_<0.05, ∆∆P<0.01, vs. normal; *P<0.05, **P<_0.01 vs. model. ML, mulberry leaf; TC, total cholesterol; TBA, total bile acid; TG, triglyceride; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol.
Figure 2.
Effects of ML on liver functions in high-fat diet-fed rats. (A) Serum AST activities; (B) serum ALT activities. (C) Representative images of liver histology. The black arrow indicates neutrophil infiltration or hepatocyte structure injury (hematoxylin-eosin staining; magnification, −200). (a) Normal; (b) model; (c) atorvastatin; (d) 0.9 g/kg ML; (e) 0.6 g/kg ML; (f) 0.3 g/kg ML. Data are presented as the mean ± standard error of the mean (n=8). ∆∆P_<0.01, vs. normal; *P<0.05, **P<_0.01 vs. model. ML, mulberry leaf; AST, aspartate aminotransferase; ALT, alanine aminotransferase.
Figure 3.
Effects of ML on liver fatty degeneration in high-fat diet-fed rats. (A) Liver TC and TG levels; (B) liver TBA levels. (C) Representative images of hepatocyte lipid droplet (oil red O staining; original magnification, −200) (a) Normal; (b) model; (c) atorvastatin; (d) 0.9 g/kg ML; (e) 0.6 g/kg ML; (f) 0.3 g/kg ML. Data are presented as the mean ± standard error of the mean (n=8). ∆P_<0.05, ∆∆P<0.01, vs. normal; *P<0.05, **P<_0.01 vs. model. ML, mulberry leaf; TC, total cholesterol; TG, triglyceride; TBA, total bile acid.
Figure 4.
Localization of SR-BI and LDL-R protein expression in livers of high-fat diet-fed rats. (A) Representative immunohistochemistry images of SR-BI in liver (HRP/DAB staining; original magnification, −200). (B) Representative immunohistochemistry images of LDL-R in liver (HRP/DAB staining; original magnification, −200). (a) Normal; (b) model; (c) atorvastatin; (d) ML. SR-BI, scavenger receptor class B type I; LDL-R, low-density lipoprotein receptor; HRP, horseradish peroxidase; DAB, 3,3′-diaminobenzidine.
Figure 5.
Expressions of cholesterol absorption, conversion and bile acid excretion-associated proteins in the livers of HFD-fed rats. (A) Western blotting images of SR-BI and LDL-R, ABCG5, ABCG8, PPARα, FXR and CYP7A1 protein expression. (B) Relative expression of SR-BI and LDL-R protein. (C) Relative expression of ABCG5 and ABCG8 protein. (D) Ratio of ABCG5/ABDG8 expression. (E) Relative expression of PPARα, FXR and CYP7A1 protein. Data are presented as the mean ± standard error of the mean (n=8). ∆P_<0.05, ∆∆P<0.01, vs. normal; *P<0.05, **P<_0.01 vs. model. SR-BI, scavenger receptor class B type I; LDL-R, low-density lipoprotein receptor; ABCG5, ATP-binding cassette transporter G5; ABCG8, ATP-binding cassette transporter G8; PPARα, peroxisome proliferator-activated receptor-α; FXR, farnesoid-X receptor; CYP7A1, cholesterol 7α-hydroxylase 1; HFD, high-fat diet; ML, mulberry leaf.
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