Side-by-side · Research reference
LivagenvsPE 22-28
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
AAnimal-StrongHUMAN-REVIEWED20/32 cited
BAnimal-StrongHUMAN-REVIEWED16/47 cited
Livagen
Khavinson Bioregulator · Hepatoprotective Tetrapeptide
Oral or SQ · Tissue-specific to liver
PE 22-28
TREK-1 Antagonist · Pre-Clinical
IP · SQ · Once Daily (animal models)Djillani 2017Pietri 2019
01Mechanism of Action
Parameter
Livagen
PE 22-28
Primary target
Hepatocyte protein synthesis machineryBrodskiĭ 2001
TREK-1 two-pore-domain potassium channelDjillani 2017Ma 2020
Pathway
Tissue-specific bioregulator → Hepatocyte stimulation → Protein synthesis normalizationBrodskiĭ 2001Khavinson 2001
TREK-1 channel blockade → Neuronal membrane depolarisation → Enhanced hippocampal excitability → Increased neuroplasticity
Downstream effect
Age-dependent enzyme normalization, hepatoprotection in fibrosis/hepatitis models, elevated protein synthesis in senescent hepatocytes
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
Feedback intact?
—
N/A — direct ion channel blockade; not receptor-mediated endocrine axis
Origin
Directed chemical synthesis from amino acid analysis of liver polypeptide preparations (Ventvil)
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
Antibody development
—
Not reported in animal studies
02Dosage Protocols
Parameter
Livagen
PE 22-28
Animal dose (oral)
Not specified in abstracts; 2-week administration protocolTimofeeva 2005
Per os administration in rats.
—
Duration (experimental)
2 weeks (enzyme study); up to 24 months (cell culture)Timofeeva 2005Brodskiĭ 2001
—
Route
Oral or subcutaneous
Resists peptidase hydrolysis, enabling oral bioavailability.Timofeeva 2005
—
Evidence basis
Animal models (rats, 1–24 months age); in vitro hepatocyte cultureTimofeeva 2005Brodskiĭ 2001Khavinson 2002
Multiple rodent RCTs; behavioral + electrophysiology endpointsDjillani 2017Qi 2018Wu 2021
Human data
None in provided literature
—
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.
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.
04Side Effects & Safety
Parameter
Livagen
PE 22-28
Reported adverse effects
None documented in animal studies
—
Human safety data
No human trials in provided literature
—
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
Absolute Contraindications
Livagen
—PE 22-28
- ·Human use — no clinical safety data available
Relative Contraindications
Livagen
—PE 22-28
- ·Cardiac arrhythmia or channelopathy (theoretical TREK-1 cardiac role)
05Administration Protocol
Parameter
Livagen
PE 22-28
1. Route selection
Oral administration supported by peptidase resistance. Subcutaneous route used in organotypic culture experiments.Timofeeva 2005Khavinson 2001
Dissolved in sterile saline or vehicle. Intraperitoneal injection, 0.3–3 µg/kg body weight. Once daily administration in rodent behavioral studies.
2. Timing
No specific timing documented. Two-week protocols used in animal models with daily administration.Timofeeva 2005
Shorter peptide length (7 AA) confers improved plasma stability vs 17-AA spadin. Exact storage conditions not detailed in published protocols.Djillani 2017
3. Age-dependent response
Elderly individuals may exhibit different enzyme normalization patterns than younger cohorts, based on rat age-stratified findings.Timofeeva 2005
Enhanced CNS bioavailability vs full spadin, likely due to smaller size. Mechanism (passive diffusion vs active transport) not fully characterized.
4. Human formulation
—
Not established — peptide synthesis methods for research use only. No pharmaceutical-grade formulation available.