AUTHOR=Qiao Kun , Liu Lina , Chen Yihui , Huang Qiongmei , Chen Bei , Wu Jingna , Huang Wenmei , Liu Zhiyu 

TITLE=Virtual screening and evaluation of bioactive peptides from Haliotis discus hannai as potential HMGCR inhibitors for hyperlipidemia treatment

JOURNAL=Frontiers in Nutrition

VOLUME=Volume 11 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2024.1525768

DOI=10.3389/fnut.2024.1525768

ISSN=2296-861X

ABSTRACT=IntroductionHyperlipidemia 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 resultsIn 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 in vitro 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.ConclusionThis study provides novel insights into developing natural drugs for hyperlipidemia; moreover, the results will facilitate the functional application of marine bioactive peptides.