l-Arabinose improves hypercholesterolemia via regulating bile acid metabolism in high-fat-high-sucrose diet-fed mice

Abstract

Background Hypercholesterolemia is closely associated with an increased risk of cardiovascular diseases. l-Arabinose exhibited hypocholesterolemia properties, but underlying mechanisms have not been sufficiently investigated. This study aimed to elucidate the mechanisms of l-arabinose on hypocholesterolemia involving the enterohepatic circulation of bile acids. Methods Thirty six-week-old male mice were randomly divided into three groups: the control group and the high-fat-high-sucrose diet (HFHSD)-fed group were gavaged with distilled water, and the l-arabinose-treated group were fed HFHSD and received 400 mg/kg/day l-arabinose for 12 weeks. Serum and liver biochemical parameters, serum and fecal bile acid, cholesterol and bile acid metabolism-related gene and protein expressions in the liver and small intestine were analyzed. Results l-Arabinose supplementation significantly reduced body weight gain, lowered circulating low-density lipoprotein cholesterol (LDL-C) while increasing high-density lipoprotein cholesterol (HDL-C) levels, and efficiently alleviated hepatic inflammation and lipid accumulations in HFHSD-fed mice. l-Arabinose inhibited cholesterol synthesis via downregulation of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). Additionally, l-arabinose might facilitate reverse cholesterol transport, evidenced by the increased mRNA expressions of low-density lipoprotein receptor (LDL-R) and scavenger receptor class B type 1 (SR-B1). Furthermore, l-arabinose modulated ileal reabsorption of bile acids mainly through downregulation of ileal bile acid-binding protein (I-BABP) and apical sodium-dependent bile acid transporter (ASBT), resulting in the promotion of hepatic synthesis of bile acids via upregulation of cholesterol-7α-hydroxylase (CYP7A1). Conclusions l-Arabinose supplementation exhibits hypocholesterolemic effects in HFHSD-fed mice primarily due to regulation of bile acid metabolism-related pathways.

Protective effects of hepatic diseases by bioactive phytochemicals in Fusarium oxysporum – A review

“…Hypercholesterolemia related to enterohepatic circulation was enhanced through regulating metabolism of bile acid by the action of arabinose in mice fed on high-fat-high-sucrose diet [ 92 ]. Practical survey was operated to study the hypolipidemic impacts of arabinose on hepatic lipid accumulation.…”

Licochalcone A Derivatives as Selective Dipeptidyl Peptidase 4 Inhibitors with Anti-Inflammatory Effects

“…As a result, 27 exhibited greater potency than kaempferol, a flavonoid-type DPP4 inhibitor studied in our previous work. 42 Analysis of the Inhibition Kinetics. To investigate the inhibitory mechanism of several potent chalcone-type compounds (6,16,22,23,24, and 27) against DPP4, comprehensive kinetic analyses and in silico analyses were performed.…”