Increased
triglyceride,
cholesterol, and
low-density lipoprotein (
LDL) levels cause
hyperlipidemia. Despite the availability of
statin-based drugs to reduce
LDL levels, additional effective treatments for reducing blood
lipid concentrations are required. Herein, soybean hydrolysate prepared via peptic and tryptic hydrolysis promoted trans-intestinal
cholesterol excretion (TICE) by increasing
ATP-binding cassette subfamily G member 5 (ABCG5) and ABCG8 expression. The
peptide sequence capable of promoting TICE was determined via HPLC and LC-MS/MS. Based on this, pure artificial
peptides were synthesized, and the efficacy of the selected
peptides was verified using cellular and hyperlipidemic mouse models. Soybean hydrolysates, including two bioactive
peptides (ALEPDHRVESEGGL and SLVNNDDRDSYRLQSGDAL), promoted TICE via the expression of ABCG5 and ABCG8 in enterocytes. They downregulated expression of hepatic
cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and
CYP8B1 via expression of
fibroblast growth factor 19 (FGF19) in a
liver X receptor α (LXRa)-dependent pathway. Administration of bioactive
peptides to hyperlipidemic mouse models by oral gavage reduced
cholesterol levels in serum via upregulation of ABCG5 and ABCG8 expression in the proximal intestine and through fecal
cholesterol excretion, upregulated FGF 15/19 expression, and suppressed hepatic
bile acid synthesis.
Oral administration of soybean-derived bioactive
peptides elicited hypolipidemic effects by increasing TICE and decreasing hepatic
cholesterol synthesis.