Effects of mulberry leaf on experimental hyperlipidemia rats induced by high‑fat diet

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.

High hydrostatic pressure extract of mulberry leaves ameliorates hypercholesterolemia via modulating hepatic microRNA-33 expression and AMPK activity in high cholesterol diet fed rats

“…It suggests that both doses of mulberry leaves used in the present study at least did not induce liver toxicity. Consistent with previous studies using hot water extract (15,16), the HHP extract of mulberry leaves significantly reduced HC-increased serum TC, TG, and LDL-levels. In addition, a dose-dependent increase in serum HDL-C level was observed in rats fed on the HC diet supplemented with the HHP extract from mulberry leaves.…”

“…Growing evidence demonstrates that multiple bioactive components such as alkaloids including 1-doxynojirimycin (1-DNJ), flavonoids, polyphenols, and polysaccharides are found in mulberry leaves which have physiologically beneficial effects (12)(13)(14). An aqueous extract of mulberry leaves inhibits the oxidation and lipid peroxidation of LDL in murine macrophage cells (9) and decreases the serum lipid profiles by regulating fatty acid oxidation, lipogenesis, and cholesterol clearance in high fat diet-fed rats or hamsters (15,16). These studies demonstrate the protective effect of mulberry leaf extract on CVDs.…”

Cis- and Trans-Palmitoleic Acid Isomers Regulate Cholesterol Metabolism in Different Ways

“…We have previously demonstrated the coordinated regulation of NPC1L1, a sterol influx transporter, and ABCG5/G8, sterol efflux transporters (Li et al, 2019). The latter two molecules form a heterodimer that promotes the metabolism of liver sterols into BAs and inhibits the absorption of sterols in the small intestine, thereby promoting cholesterol excretion (Ge et al, 2008;Hong and Tontonoz, 2014;Wang et al, 2015;Huang et al, 2018c). ABCG5 and ABCG8 are members of the ATP-binding cassette subfamily of transmembrane transporters and are mainly expressed in intestinal epithelial cells and liver cells.…”

Effect of Zanthoxylum alkylamides on lipid metabolism and its mechanism in rats fed with a high‐fat diet

“…Its main manifestations include elevated TC, TG, and LDL‐C contents and reduced HDL‐C content in blood. The pathogenesis of hyperlipidemia is complex, and overnutrition caused by a long‐term high‐fat diet plays a key role in the progression of the disease (Gong et al., 2020; Huang et al., 2018). The results of this study showed that TG, cholesterol, and LDL cholesterol concentrations in rat plasma increased significantly after a long‐term high‐fat diet.…”

“…Its main manifestations include elevated TC, TG, and LDL-C contents and reduced HDL-C content in blood. The pathogenesis of hyperlipidemia is complex, and overnutrition caused by a long-term high-fat diet plays a key role in the progression of the disease (Gong et al, 2020;Huang et al, 2018).…”