An 11-amino-acid peptide (GQEDYDRLRPL) from the mushroom Stropharia rugosoannulata inhibited the blood pressure enzyme ACE with an IC50 of 164 μmol/L and lowered blood pressure in animals.
IC50: 164.41 μmol/LThe mushroom-derived peptide GQEDYDRLRPL inhibited ACE at micromolar concentrations and showed strong binding with almost all of its residues contacting the enzyme.
What the researchers found
From 27 undecapeptides screened by molecular docking, GQEDYDRLRPL was identified as the best ACE inhibitor from S. rugosoannulata. Ten of its eleven amino acid residues interacted with the ACE receptor. The peptide bound ACE with strong affinity — kinetic binding constant of 9.26 × 10⁻⁷ M and thermodynamic binding constant of 3.06 × 10⁻⁶ M. Binding was exothermic and enthalpy-driven.
The peptide had an in vitro IC50 of 164.41 μmol/L for ACE inhibition. In vivo, oral gavage administration at low doses showed superior antihypertensive effects compared to controls. Molecular dynamics simulations revealed that the peptide caused significant structural fluctuations in ACE residues 340-355, which include two residues in the enzyme's active pocket.
Why it matters
Hypertension affects over a billion people worldwide, and while ACE inhibitor drugs are effective, natural food-derived alternatives are increasingly sought for their potential as functional foods or supplements with fewer side effects. This mushroom-derived peptide demonstrates that edible fungi can be sources of potent ACE-inhibitory peptides, and the comprehensive structure-activity analysis provides a framework for optimizing such peptides.
How the study worked
Twenty-seven undecapeptides from S. rugosoannulata were screened using molecular docking against the ACE receptor. The lead peptide GQEDYDRLRPL was characterized using molecular dynamics simulations, surface plasmon resonance (for kinetic binding), isothermal titration calorimetry (for thermodynamic binding), and in vitro ACE inhibition assays. Antihypertensive activity was validated in vivo through low-dose oral gavage in animals.
What this study cannot tell us
The IC50 of 164.41 μmol/L is relatively high compared to pharmaceutical ACE inhibitors (which work at nanomolar concentrations). It is unclear whether the peptide survives complete gastrointestinal digestion in its active form. The in vivo antihypertensive data is not detailed in the abstract (specific blood pressure reductions and animal model not described). Long-term safety and efficacy data are not available.
How to read the evidence
This study combines computational screening, detailed binding characterization, in vitro activity assays, and in vivo validation — a comprehensive approach for a natural product peptide study. However, the evidence remains preclinical, and the relatively high IC50 compared to pharmaceutical ACE inhibitors limits direct clinical applicability.
When this study was published
Published in 2023, this is recent research in the active field of food-derived bioactive peptides. Mushroom-derived peptides are an emerging area of interest within this field.
The bigger picture
Food-derived ACE-inhibitory peptides have been extensively studied from sources like milk, fish, and soy, with some (lactotripeptides) reaching commercial functional food status. Mushrooms are a less-explored source that could offer unique peptide sequences. The comprehensive approach in this study — from computational screening through binding characterization to in vivo validation — represents the current standard for developing bioactive peptide candidates from natural sources.
Questions still open
- Does GQEDYDRLRPL survive gastrointestinal digestion intact, or is it broken down into smaller fragments that may or may not retain ACE-inhibitory activity?
- How does the antihypertensive potency of this mushroom peptide compare to established food-derived ACE-inhibitory peptides like lactotripeptides?
- Could this peptide be concentrated from mushroom extracts at levels sufficient for functional food applications?
Common questions
What is ACE and why is it a target for blood pressure drugs?
Could eating this mushroom lower blood pressure?
Read the original research
Structure-Activity Relationship of Novel ACE Inhibitory Undecapeptides from Stropharia rugosoannulata by Molecular Interactions and Activity Analyses.
Foods (Basel, Switzerland), 12(18)
Citation
Li, Wen; Chen, Wanchao; Wang, Jinbin; Li, Zhengpeng; Zhang, Zhong; Wu, Di; Yan, Mengqiu; Ma, Haile; Yang, Yan. (2023). Structure-Activity Relationship of Novel ACE Inhibitory Undecapeptides from Stropharia rugosoannulata by Molecular Interactions and Activity Analyses.. Foods (Basel, Switzerland), 12(18). https://doi.org/10.3390/foods12183461