Journal
JOURNAL OF FUNCTIONAL FOODS
Volume 77, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jff.2020.104328
Keywords
His-Pro-Pro; Ser-Gly-Gln-Arg; Silkworm pupae; 3-Hydroxy-3-methyl glutaryl coenzyme A reductase; Molecular docking
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Funding
- National Natural Science Foundation of China [31101390]
- Zhejiang Provincial Natural Science Foundation of China [LY 13C200015, LQ 13C200005]
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Peptides with high HMGCR inhibitory activity were screened from silkworm pupae protein hydrolysates, and in vitro studies confirmed HPP and SGQR as inhibitors of HMGCR. Molecular docking revealed key interactions responsible for their role in improving hypercholesterolemia, suggesting potential therapeutic benefits.
To screen several peptides that could possibly inhibit the biosynthesis of cholesterol, we selected peptides with high 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR) inhibitory activity from silkworm pupae protein hydrolysates (SPPHs). SPPH was obtained by hydrolysing the proteins with neutral proteinase, and filtered to <3, 3-5 and >5 kDa fractions. Fraction 4 (SPP) with the highest HMGCR inhibitory activity was acquired from the ultrafiltrate (<3 kDa) by Sephadex G-15 filtration. In silico predictions were executed to identify peptides with HMGCR inhibitory activity. In vitro studies showed that His-Pro-Pro (HPP) and Ser-Gly-Gln-Arg (SGQR) inhibited activity of HMGCR, decreased mRNA and protein expression of HMGCR and squalene synthase, and activated the expression of low-density lipoprotein receptor. Molecular docking revealed that H-bonding interactions were responsible in HPP and SGQR for their role in improving hypercholesterolemia. Our findings suggest that HPP and SGQR have great potential in improving hypercholesterolemia.
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