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

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 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.

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