PyrGF and GSTLN peptides enhance pravastatin's inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme

• Published in: Food bioscience Vol. 44; p. 101451
• Main Authors: da Silva, Jaff Ribeiro, de Cerqueira e Silva, Mariana Barros, Philadelpho, Biane Oliveira, de Souza, Victória Cruz, dos Santos, Johnnie Elton Machado, Castilho, Marcelo Santos, de Souza Ferreira, Ederlan, Cilli, Eduardo Maffud
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01-12-2021
• Subjects: Bioactive peptides; Cholesterol; Concentration–response effect; HMGCoAR inhibitor; Molecular docking; Concentration–response effect; Bioactive peptides; HMGCoAR inhibitor; Cholesterol; Molecular docking
• ISSN: 2212-4292; 2212-4306
• DOI: 10.1016/j.fbio.2021.101451

Two newly designed peptides, Pyr-GF and GSTLN, enhance pravastatin inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCoAR). In silico experiments have demonstrated the interaction of these peptides with the catalytic and NADPH sites of HMGCoAR. In vitro, the Pyr-GF (IC50 = 117.4 μM) and GSTLN (IC50 = 278.1 μM) peptides exhibit dose-dependent inhibition on the HMGCoAR activity, and the effects are more significant than those observed for original peptides obtained from cowpea and adzuki beans. Compared to pravastatin alone, the Pyr-GF/pravastatin combination produced a small decrease (8%) in HMGCoAR activity, whereas the GSTLN/pravastatin combination produced a significant decrease of 41% on HMGCoAR activity. The association between Pyr-GF/GSTLN peptides decreased the IC50 to 71.8 μM. These results suggest their interaction with different sites; Pyr-GF and pravastatin mainly act on the catalytic site and GSTLN on the NADPH site. Hence, the Pyr-GF and GSTLN peptides and their combination exhibit a cholesterol-lowering effect and act as adjuvants upon association with pravastatin.
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•In silico interactions of Pyr-GF and GSTLN peptides with HMG-CoA reductase sites are established.•Pyr-GF (IC50 = 117.4 μM) and GSTLN (IC50 = 278.1 μM) peptides exhibit dose-dependent inhibitory effects in vitro.•GSTLN/pravastatin combination decreases HMGCoAR activity by 41% more than solely pravastatin.•Pyr-GF and GSTLN in association with pravastatin act as adjuvants.•Pyr-GF and GSTLN peptides or their combination exhibit cholesterol-lowering effect.