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Silkworm Enzyme Hydrolysates Improve Memory in MCI Models via CREB-BDNF Signaling and Enhanced Brain Mitochondrial
Yoo-Hee Kim1, Nguyen Phuong1, Nguyen Minh Anh Hoang2
1Ilsong Institute of Life Science, Hallym University, Seoul 07247, Republic of Korea.
Nutrients
|June 27, 2025
Summary
Enzymatic hydrolysis of HongJam (steamed mature silkworms) significantly boosted cognitive function in mice. Enzyme-treated HongJam (GS-EHS) improved memory and mitochondrial function, offering a potent, low-dose cognitive enhancer.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- HongJam, derived from steamed mature silkworms, is explored for cognitive benefits.
- Enzymatic hydrolysis is investigated as a method to enhance HongJam's bioactivity.
Purpose of the Study:
- To determine if enzymatic hydrolysis improves the cognitive effects of HongJam.
- To elucidate the mechanisms behind these enhanced cognitive benefits.
- To identify a marker compound for quality control of enzyme-treated HongJam.
Main Methods:
- Mice were supplemented with Golden Silk HongJam (GS) or its enzyme hydrolysates (GS-EHS).
- Cognitive function was assessed using behavioral tests.
- Molecular mechanisms involving signaling pathways, mitochondrial function, oxidative stress, and programmed cell death were analyzed.
- Mass spectrometry was used to identify potential marker compounds.
Main Results:
- GS-EHS demonstrated comparable or superior cognitive enhancement at lower doses compared to GS.
- GS-EHS activated the cyclic AMP response element binding protein/brain-derived neurotrophic factor pathway.
- GS-EHS mitigated scopolamine-induced mitochondrial dysfunction, enhanced ATP production, and increased esterase activity.
- GS-EHS reduced reactive oxygen species and modulated programmed cell death pathways (apoptosis, autophagy, unfolded protein response), decreasing endoplasmic reticulum stress and neuroinflammation.
- Glycine-tyrosine dipeptide was identified as a potential bioactive marker.
Conclusions:
- Enzyme-treated HongJam (GS-EHS) effectively enhances cognitive function through improved mitochondrial activity, reduced oxidative stress, and regulated programmed cell death.
- Enzymatic hydrolysis increases the bioavailability of active compounds in HongJam, leading to enhanced efficacy at lower doses.
- Glycine-tyrosine dipeptide can serve as a marker compound for standardizing enzyme-treated HongJam for cognitive-enhancing properties.
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