The peptide VGAW from fermented soybean (Douchi) potently inhibited the blood pressure enzyme ACE (IC50 46.6 µM) and significantly reduced blood pressure in hypertensive rats.
IC50: 46.6 µMThe tetrapeptide VGAW competitively inhibited ACE and reduced blood pressure in hypertensive rats at doses as low as 12.5 mg/kg
What the researchers found
From Douchi hydrolysate, five ACE inhibitory peptides were identified: LF, VVF, VGAW, GLFG, and NGK. The tetrapeptide VGAW was the most potent:
- ACE inhibition IC50: 46.6 ± 5.2 µM (competitive inhibitor)
- Excellent thermal and pH stability
- Molecular docking revealed 8 hydrogen bonds between VGAW and ACE
- Lineweaver-Burk plots confirmed competitive inhibition mechanism
- Significantly reduced blood pressure in spontaneously hypertensive rats at 12.5, 25, and 50 mg/kg doses
The optimal enzyme combination for generating these peptides was pepsin-trypsin-chymotrypsin, outperforming 10 single enzymes and 3 other combinations.
Why it matters
Finding effective blood pressure-lowering peptides in a traditional food product like Douchi validates centuries of dietary wisdom with modern science. Food-derived ACE inhibitory peptides could offer a natural, side-effect-free approach to blood pressure management as functional food ingredients or supplements.
How the study worked
Ten single enzymes and four combinations were tested for Douchi hydrolysis. Hydrolysates were purified using Sephadex G-15 gel filtration and reversed-phase HPLC. Peptides were identified via LC-MS/MS. ACE inhibition was measured with IC50 values and Lineweaver-Burk kinetic analysis. Molecular docking simulated peptide-ACE interactions. In vivo antihypertensive activity was tested in spontaneously hypertensive rats at three dose levels.
What this study cannot tell us
The in vivo testing was done in spontaneously hypertensive rats, which may not fully represent human hypertension. The oral bioavailability of VGAW in humans is unknown — it may be degraded during human digestion despite showing enzyme stability in lab tests. No human clinical trials were conducted. The amount of VGAW naturally present in Douchi versus what was isolated through intensive hydrolysis may differ significantly.
How to read the evidence
This study provides both in vitro mechanistic data and in vivo animal evidence, placing it at a moderate preclinical evidence level. The competitive inhibition mechanism is well-characterized through multiple analytical approaches.
When this study was published
Published in 2024, this study contributes to the active field of food-derived ACE inhibitory peptides, building on decades of research into soy-based bioactive compounds.
The bigger picture
Food-derived bioactive peptides are a growing field bridging nutrition and medicine. Discovering potent ACE inhibitory peptides in traditional fermented foods like Douchi supports the concept of 'food as medicine' and could lead to nutraceutical products that help manage blood pressure through diet rather than drugs.
Questions still open
- Does VGAW survive human gastrointestinal digestion and maintain ACE inhibitory activity?
- What concentration of VGAW is naturally present in commercially available Douchi?
- Could VGAW be developed into an oral supplement for blood pressure management?
Common questions
Can eating Douchi lower blood pressure?
How does VGAW compare to blood pressure medications?
Read the original research
A novel ACE inhibitory peptide from Douchi hydrolysate: Stability, inhibition mechanism, and antihypertensive potential in spontaneously hypertensive rats.
Food chemistry, 460(Pt 3), 140734
Citation
Li, Jianfei; Hu, Haohan; Chen, Xiya; Zhu, Haiting; Zhang, Wenhao; Tai, Zhiyuan; Yu, Xiaodong; He, Qiyi. (2024). A novel ACE inhibitory peptide from Douchi hydrolysate: Stability, inhibition mechanism, and antihypertensive potential in spontaneously hypertensive rats.. Food chemistry, 460(Pt 3), 140734. https://doi.org/10.1016/j.foodchem.2024.140734