Side-by-side · Research reference
PE 22-28vsVesugen
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
AAnimal-StrongHUMAN-REVIEWED16/47 cited
BAnimal-MechanisticHUMAN-REVIEWED5/43 cited
PE 22-28
TREK-1 Antagonist · Pre-Clinical
IP · SQ · Once Daily (animal models)Djillani 2017Pietri 2019
Vesugen
Bioregulatory Tripeptide · Vascular Endothelium
3 AATripeptide
Endothelin-1 ↓Atherosclerotic tissue
Ki-67 ↑Aged endothelium
SQ / IM · Protocol varies
01Mechanism of Action
Parameter
PE 22-28
Vesugen
Primary target
TREK-1 two-pore-domain potassium channelDjillani 2017Ma 2020
Vascular endothelial cell nucleus — MKI67 gene promoter
Pathway
TREK-1 channel blockade → Neuronal membrane depolarisation → Enhanced hippocampal excitability → Increased neuroplasticity
KED → MKI67 promoter interaction (CATC binding motif -14 to +12 bp) → Ki-67 proliferation protein ↑
Downstream effect
Antidepressant-like activity in forced swim test and tail suspension test; reduced A1-like reactive astrocyte activation; neuroprotection via NF-κB pathway modulationDjillani 2017Cong 2023Wu 2021
Normalised endothelin-1 expression in atherosclerotic/restenotic endothelium, restored connexin expression for cell-cell communication, enhanced proliferative capacity in senescent endothelial culturesKozlov 2016Khavinson 2014
Feedback intact?
N/A — direct ion channel blockade; not receptor-mediated endocrine axis
Not applicable — does not operate via hormone axis
Origin
Synthetic truncation of spadin (PE 12-28), itself derived from the sortilin propeptide C-terminus. Residues 22-28: Val-Val-Arg-Gly-Trp-Leu-Arg.Djillani 2017Mazella 2018
Khavinson bioregulatory peptide school — designed as tissue-specific (vascular) cytomodulator
Antibody development
Not reported in animal studies
—
02Dosage Protocols
Parameter
PE 22-28
Vesugen
Animal dose (antidepressant)
0.3–3 µg/kg IP
Effective in forced swim test, tail suspension test, CUMS models.
—
Animal dose (neuroprotection)
0.03 µg/kg IPPietri 2019
Low-dose TREK-1 activation post-stroke for 7 days, then high-dose blockade.
—
Frequency
Once daily
Sustained antidepressant effect over 7+ days.
Not specified in available literature
Onset (animal)
Within hours (acute); full effect 4–7 days
—
Comparison to fluoxetine
PE 22-28 outperforms fluoxetine in CUMS-sensitive rats by day 7
Chronic administration shows superior long-term efficacy.
—
Human equivalent (extrapolated)
Not established — no clinical trials
Allometric scaling from rodent data unavailable.
—
Evidence basis
Multiple rodent RCTs; behavioral + electrophysiology endpointsDjillani 2017Qi 2018Wu 2021
Animal models (atherosclerosis, restenosis, aging) · Russian case series
Standard dose (reported)
—
Not standardised — Russian clinical case series
Protocols vary; no FDA-approved regimen.
Route
—
Subcutaneous or intramuscular
Duration
—
Case series report treatment courses in elderly arterial insufficiency
Half-life
—
Not reported
Tripeptides typically cleared rapidly.
04Side Effects & Safety
Parameter
PE 22-28
Vesugen
Toxicity (animal)
No adverse effects reported at therapeutic doses
—
Cardiovascular (theoretical)
TREK-1 expressed in cardiac tissue; arrhythmia risk unclear
—
Weight change
Not reported in animal studies
—
Neurological
No seizures or behavioral abnormalities noted
—
Long-term safety
Unknown — longest animal study 28 days
Unknown — no long-term RCT data
Reported adverse events
—
None documented in available abstracts
Injection site
—
Assumed minimal — typical for small peptides
Epigenetic mechanism risk
—
Theoretical concern: direct gene promoter interaction — proliferative effects in non-target tissues not characterised
Absolute Contraindications
PE 22-28
- ·Human use — no clinical safety data available
Vesugen
—Relative Contraindications
PE 22-28
- ·Cardiac arrhythmia or channelopathy (theoretical TREK-1 cardiac role)
Vesugen
- ·Active malignancy — proliferative mechanism (Ki-67 upregulation) untested in oncologic context
05Administration Protocol
Parameter
PE 22-28
Vesugen
1. Animal protocol (IP)
Dissolved in sterile saline or vehicle. Intraperitoneal injection, 0.3–3 µg/kg body weight. Once daily administration in rodent behavioral studies.
Lyophilised powder reconstituted with sterile water or bacteriostatic water per supplier protocol. No standardised formulation.
2. Stability
Shorter peptide length (7 AA) confers improved plasma stability vs 17-AA spadin. Exact storage conditions not detailed in published protocols.Djillani 2017
Subcutaneous (abdomen, thigh) or intramuscular. Rotate sites if multi-dose protocol.
3. BBB penetration
Enhanced CNS bioavailability vs full spadin, likely due to smaller size. Mechanism (passive diffusion vs active transport) not fully characterized.
No reported circadian or fasting requirement. Russian protocols typically integrated into geroprotective regimens.
4. Human formulation
Not established — peptide synthesis methods for research use only. No pharmaceutical-grade formulation available.
Lyophilised: refrigerate 2–8 °C, light-protected. Reconstituted: use immediately or refrigerate per supplier guidance (typically <7 days).
06Stack Synergy
PE 22-28
— no documented stacks
Vesugen
+ Thymalin
Multi-pathwayBoth from Khavinson bioregulatory school. Thymalin targets thymic/immune axis, Vesugen targets vascular endothelium. Rationale: multi-system geroprotection in elderly — immune senescence + vascular aging. Documented in Khavinson-tradition protocols combining tissue-specific peptides for poly-organ rejuvenation. No direct synergy study; combinatorial logic based on distinct target tissues.
- Vesugen
- Per protocol (SQ/IM)
- Thymalin
- Per protocol (SQ/IM)
- Frequency
- Sequential or concurrent per geroprotective protocol
- Primary benefit
- Multi-system age-related decline mitigation (vascular + immune)