Evaluation of hypolipidemic peptide (Val-Phe-Val-Arg-Asn) virtual screened from chickpea peptides by pharmacophore model in high-fat diet-induced obese rat

• Main Authors: Wen Shi, Tao Hou, Danjun Guo, Hui He
• Format: Article
• Language: English
• Published: Elsevier 2019-03-01
• Series: Journal of Functional Foods
• Subjects: Chickpea peptides (ChPs); Hypolipidemic effects; HMGR inhibitor; Pharmacophore modeling; Val-Phe-Val-Arg-Asn (VFVRN)
• Online Access: http://www.sciencedirect.com/science/article/pii/S1756464619300015

Chickpea peptides (ChPs) were found to significantly decrease serum total cholesterol (TC), total triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) content, and increase serum high-density lipoprotein cholesterol (HDL-C) content (P < 0.05) in high fat diet-induced obese rats. The activities of fatty acid synthetase (FAS) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) could be significantly inhibited by ChPs. Additionally, peroxisome proliferator-activated receptors (PPAR)α and LDL receptor (LDLR) expressions were up-regulated, and sterol regulatory element-binding protein (SREBP)-2 expression was down-regulated by ChPs significantly (P < 0.05). Fecal TC and bile acid (TBA) were also found to be increased significantly (P < 0.05) in ChPs with high-fat diet treatment groups. Moreover, the micellar solubility of cholesterol decreased after the treatment with ChPs in vitro. A reductase (HMGR) inhibitor (VFVRN) was found using pharmacophore model. VFVRN was found to have high hypolipidemic effects by using Hypo1, which was a novel scaffold of HMGR. VFVRN was confirmed in HepG2 cell that it could inhibit the TC synthesis by decreasing the expressions of SREBP-1c, SREBP-2, liver X receptor (LXR)α and HMGR.