Virtual Screening and Evaluation of Bioactive Peptides from As Potential HMGCR Inhibitors for Hyperlipidemia Treatment

Overview

Journal Front Nutr

Date 2025 Jan 15

PMID 39811675

Authors

Kun Qiao

Lina Liu

Yihui Chen

Qiongmei Huang

Bei Chen

Jingna Wu

Wenmei Huang

Zhiyu Liu

Affiliations

Soon will be listed here.

Abstract

Introduction: Hyperlipidemia remains a major disease threatening global public health. The morbidity and mortality associated with cardiovascular diseases have been increasing. The inhibition of 3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), a key enzyme in the cholesterol synthesis pathway, can effectively reduce cholesterol levels.

Methods And Results: In this study, the most suitable protease for preparing HMGCR inhibitory peptides was screened using the evaluation indexes of peptide yield and HMGCR inhibition rate. Peptide sequences with molecular weights <1 kDa were identified, and peptide fragments were docked with HMGCR for virtual screening. The inhibitory effects of these peptides on HMGCR activity were evaluated using a high-fat Hep-G2 cell model. The screened peptides possessed significant HMGCR inhibitory activity and reduced cholesterol micelle solubility and total cholesterol and triglyceride levels in hyperlipidemic Hep-G2 cells.

Conclusion: This study provides novel insights into developing natural drugs for hyperlipidemia; moreover, the results will facilitate the functional application of marine bioactive peptides.

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