The Regulation of Alfalfa Saponin Extract on Key Genes Involved in Hepatic Cholesterol Metabolism in Hyperlipidemic Rats

Abstract

To investigate the cholesterol-lowering effects of alfalfa saponin extract (ASE) and its regulation mechanism on some key genes involved in cholesterol metabolism, 40 healthy 7 weeks old male Sprague Dawley (SD) rats were randomly divided into four groups with 10 rats in each group: control group, hyperlipidemic group, ASE treatment group, ASE prevention group. The body weight gain, relative liver weight and serum lipid 1evels of rats were determined. Total cholesterol (TC) and total bile acids (TBA) levels in liver and feces were also measured. Furthermore, the activity and mRNA expressions of Hmgcr, Acat2, Cyp7a1 and Ldlr were investigated. The results showed the following: (1) The abnormal serum lipid levels in hyperlipidemic rats were ameliorated by ASE administration (both ASE prevention group and treatment group) (P<0.05). (2) Both ASE administration to hyperlipidemic rats significantly reduced liver TC and increased liver TBA level (P<0.05). TC and TBA levels in feces of hyperlipidemic rats were remarkably elevated by both ASE administration (P<0.05). (3) mRNA expressions of Hmgcr and Acat2 in the liver of hyperlipidemic rats were remarkably down-regulated (P<0.05), as well as mRNA expressions of Cyp7a1 and Ldlr were dramatically up-regulated by both ASE administration (P<0.05). The activities of these enzymes also paralleled the observed changes in mRNA levels. (4) There was no significant difference between ASE treatment and ASE prevention group for most parameters evaluated. Our present study indicated that ASE had cholesterol-lowering effects. The possible mechanism could be attributed to (1) the down-regulation of Hmgcr and Acat2, as well as up-regulation of Cyp7a1 and Ldlr in the liver of hyperlipidemic rats, which was involved in cholesterol biosynthesis, uptake, and efflux pathway; (2) the increase in excretion of cholesterol. The findings in our study suggested ASE had great potential usefulness as a natural agent for treating hyperlipidemia.

Effects of alfalfa saponin extract on mRNA expression of Ldlr, LXRα, and FXR in BRL cells

“…In our study, Ldlr mRNA increased both in normal and hyperlipidemic BRL cells, indicating that ASE could ameliorate hepatocyte steatosis by up-regulating Ldlr. These data agree with our previous study showing that the cholesterol-lowering effects of ASE may be attributed to its regulation on some key genes involved in cholesterol metabolism in hyperlipidemic rats, such as up-regulation of Ldlr in the liver of hyperlipidemic rats (Shi et al, 2014).…”

“…It was possible that ASE was a kind of agent that decreased the expression of FXR, thus increasing the mRNA expression of Cyp7a1 and as a result, enhancing the catabolic pathway of cholesterol. Our previous studies have shown that ASE could up-regulate the mRNA expression of Cyp7a1 in rats and hens (Shi et al, 2014;Zhou et al, 2014). The findings also suggested that FXR could be a potential therapeutic target in anticholesterolemic effects induced by ASE.…”

“…The literature suggests that AS can significantly reduce serum TC, TG, and LDL-C in animals (Al-Bar et al, 1993;Francis et al, 2001;Santoso et al, 2004) and similar outcomes in weaning piglets were reported by Wang (2007). Shi et al (2014) concluded that the cholesterol-lowering effects of ASE were mediated by regulating gene expression involved in cholesterol metabolism. However, how ASE works at the cellular level is unclear.…”

Pengaruh Pemberian Ekstrak Buah Naga Merah (Hylocereus polyrhizus) Terhadap Gambaran Spermatogenesis Tikus Putih (Rattus norvegicus) Galur Wistar yang Diinduksi Pakan Tinggi Lemak

“…19 Saponin dan Triterpenoid bekerja dengan menghambat HMG KoA reduktase. 19,35 Senyawa fenol, betasianin, dan asam askorbat menetralkan radikal bebas dan radikal perioksida sehingga stres oksidatif menurun. 19 Flavonoid secara langsung mendonorkan ion hidrogen untuk stabilisasi radikal bebas dan secara tidak langsung merangsang ekspresi gen antioksidan.…”

Phytochemical evaluation and antibacterial effects of Medicago sativa, Onosma sericeum, Parietaria judaica L., Phlomis persica and Echinophora platyloba DC. on Enterococcus faecalis

“…sativa, also known as alfalfa and lucerne, comes from the Fabaceae family (Sadowska et al, 2014 Russia, North Africa and China because of their high vitamin content (Shi et al, 2014). It produces secondary metabolites, such as coumarins, isoflavones, naphthoquinones, alkaloids and saponins, that have nematocidal, cytotoxic and antimicrobial effects (Sadowska et al, 2014).…”