Ovagen
Ovagen (Thr-Glu-Asp-Phe) is a synthetic tetrapeptide bioregulator targeting hepatic and gastrointestinal tissue, researched for hepatoprotective effects, liver aging, and gene expression modulation in hepatocytes. Developed at the St. Petersburg Institute of Bioregulation and Gerontology.
Ovagen is a synthetic tetrapeptide (Thr-Glu-Asp-Phe, or TEDF) classified as a bioregulatory peptide with primary effects on liver and gastrointestinal tract tissue. Despite its name, which occasionally causes confusion with ovarian function, ovagen's documented research activity centers on hepatocytes and GI epithelial cells.
Overview
Ovagen is one of the defined-sequence tetrapeptide bioregulators from Khavinson's research program, alongside cardiogen (AEDR), cortagen (AEDP), bronchogen (AEDL), and others. Each tetrapeptide was identified through systematic screening of tissue-derived peptide fractions for biological activity in their respective target organs.
The peptide's primary research applications involve liver function and hepatoprotection, particularly in the context of aging. Studies have demonstrated that ovagen modulates gene expression in hepatocyte cultures, influencing pathways related to detoxification, protein synthesis, and cellular stress responses. Additional research has explored its effects on gastrointestinal epithelial cells, consistent with the shared embryological origin of liver and GI tract tissues.
Mechanism of Action
Ovagen is proposed to interact directly with DNA sequences in hepatocyte chromatin, consistent with the broader mechanism described for Khavinson's tetrapeptide bioregulators. Research has shown that short peptides can bind to specific DNA sequences and modulate chromatin condensation, influencing gene transcription.
In liver tissue specifically, ovagen has been shown to:
- Modulate expression of genes involved in detoxification enzyme systems (cytochrome P450 family)
- Influence expression of anti-apoptotic factors in hepatocytes
- Regulate synthesis of acute-phase proteins associated with hepatic stress responses
- Affect chromatin structure in hepatocyte nuclei, as demonstrated by changes in heterochromatin/euchromatin ratios
Khavinson and colleagues demonstrated that the TEDF sequence shows preferential binding to DNA regions associated with liver-specific gene promoters, providing a molecular basis for its tissue selectivity (Khavinson et al., 2012).
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Research
Hepatoprotection and Liver Aging
Studies in aged animal models demonstrated that ovagen administration partially restored liver function parameters that decline with aging, including albumin synthesis rates, detoxification capacity, and hepatocyte proliferative potential. Histological analysis showed reduced lipofuscin accumulation and improved hepatocyte morphology in treated animals compared to age-matched controls.
Chalisova et al. examined the effects of ovagen on liver tissue explant cultures from young and old rats, finding that the peptide stimulated cellular proliferation and reduced markers of senescence in hepatocyte cultures from aged donors (Chalisova et al., 2008, Adv Gerontol).
Gastrointestinal Tract Effects
Research on ovagen's effects in GI tissue has shown modulation of epithelial cell function in the stomach and intestinal mucosa. In animal models of gastric mucosal damage, peptide bioregulators including ovagen demonstrated protective effects, reducing ulcer formation and accelerating mucosal healing. These findings are consistent with the peptide's proposed role in supporting epithelial cell turnover and differentiation in tissues derived from the endodermal lineage.
Gene Expression Modulation in Hepatocytes
A key area of ovagen research has been its effects on gene expression profiles in liver cells. Studies using cultured human hepatocytes demonstrated changes in expression of multiple gene families following ovagen treatment, including upregulation of genes involved in protein synthesis, detoxification, and antioxidant defense. Notably, expression of SOD2 (superoxide dismutase) and several glutathione pathway genes was increased, suggesting enhanced cellular protection against oxidative damage (Khavinson et al., 2012).
Safety Profile
Ovagen has been studied in cell culture systems and animal models with no reported adverse effects. As a short tetrapeptide composed of common amino acids, it is expected to have low inherent toxicity and rapid metabolic clearance. The peptide has been available as a dietary supplement in Russia through the Cytomed product line. No formal human clinical safety trials meeting international standards have been published. Individuals with active liver disease should consult medical professionals before use.
Pharmacokinetic Profile
- Half-life
- Not established
Quick Start
- Typical Dose
- 10-20mg daily
- Frequency
- Daily for 10-20 days per cycle
- Route
- Oral, Subcutaneous
- Cycle Length
- 10-20 days
- Storage
- Capsules at room temperature; reconstituted injectable at 2-8°C refrigerated
Molecular Structure
- Formula
- C22H29N4O10
- Weight
- 375 Da
- Length
- 3 amino acids
- CAS
- Not available
Research Indications
Liver Support
Reduces long-term fibrosis development in liver tissue.
Protects liver through gene expression regulation.
GI Protection
Helps protect GI mucosal layer from various insults.
May protect GI tract from antibiotic-induced damage.
Protects against environmental toxin effects on GI tract.
Anti-Aging
Addresses age-related liver changes through bioregulation.
Supports GI tract function during aging.
Research Protocols
oral
Available in capsule form for oral administration. As a tripeptide, Ovagen is transported via PEPT1/PEPT2 transporters for targeted delivery to liver and GI tissue. Typical protocol involves 10-20 day cycles.
| Goal | Dose | Frequency | Duration |
|---|---|---|---|
| Standard protocol | 10-20 mg | Daily for 10-20 days | —(Route: Oral capsules) |
subcutaneous Injection
Liver bioregulator. Very low dose protocol over 16 weeks.
| Goal | Dose | Frequency | Duration |
|---|---|---|---|
| Week 1-2 | 10 mcg | Once daily | Weeks 1-2 |
| Week 3-4 | 20 mcg | Once daily | Weeks 3-4 |
| Week 5-6 | 50 mcg | Once daily | Weeks 5-6 |
| Week 7-8 | 100 mcg | Once daily | Weeks 7-8 |
| Maintenance | 100-150 mcg | Once daily | Weeks 9-16(One 20 mg vial lasts full 16-week cycle) |
Reconstitution Guide (20mg vial + 2mL BAC water)
- Wipe vial tops with alcohol swab
- Draw 2.0 mL bacteriostatic water into syringe
- Inject slowly down the inside wall of the peptide vial
- Gently swirl to dissolve — never shake
- Resulting concentration: 10 mg/mL
- For 10 mcg dose: draw 0.1 units (0.001 mL) — use 30-unit insulin syringe for accuracy
- For 50 mcg dose: draw 0.5 units (0.005 mL)
- For 100 mcg dose: draw 1 unit (0.01 mL)
- For 150 mcg dose: draw 1.5 units (0.015 mL)
- Aliquot into multiple vials and freeze unused portions
- Store reconstituted vial refrigerated at 2-8°C
Interactions
Peptide Interactions
Ovagen is one of the defined-sequence tetrapeptide bioregulators from Khavinson's research program, alongside cardiogen (AEDR), cortagen (AEDP), bronchogen (AEDL), and others.
Ovagen is one of the defined-sequence tetrapeptide bioregulators from Khavinson's research program, alongside cardiogen (AEDR), cortagen (AEDP), bronchogen (AEDL), and others.
Ovagen is one of the defined-sequence tetrapeptide bioregulators from Khavinson's research program, alongside cardiogen (AEDR), cortagen (AEDP), bronchogen (AEDL), and others.
What to Expect
What to Expect
Gene expression modulation begins
Effects persist due to epigenetic changes
Liver and GI function improvements
Cumulative benefits with periodic cycles
Safety Profile
Common Side Effects
- Generally well-tolerated
- Minimal side effects reported
Contraindications
- Active liver emergencies (seek medical care)
- Known hypersensitivity
- Pregnancy or breastfeeding
Discontinue If
- Allergic reactions
- Unusual GI or liver symptoms
Quality Indicators
What to look for
- White powder or capsules
- Clear solution if reconstituted
- Proper packaging and labeling
Caution
- Unknown source or purity
- Do not confuse with FSH derivative of same name
Red flags
- Discoloration
- Unusual odor
- Damaged packaging
Frequently Asked Questions
References (9)
- [1][Khavinson VKh et al. (2012). Mechanisms underlying geroprotective effects of peptides. Bull Exp Biol Med (2012)
- [1]Khavinson Peptide Bioregulators Overview (2020)
- [2]POT Family Transporters and Peptide Bioregulators (2018)
- [3]Peptide Bioregulators and Liver Fibrosis (2019)
- [2]Chalisova NI et al. (2008). Effect of short peptides on the development of tissue cultures of the liver from young and old rats. Adv Gerontol (Uspekhi Gerontol) (2008)
- [5]Khavinson VKh (2002). Peptides and ageing. Neuro Endocrinol Lett (2002)
- [3][Ashapkin V et al. (2020). Gene expression in human mesenchymal stem cell aging cultures: modulation by short peptides. Mol Biol Rep (2020)
- [4][Khavinson VKh & Malinin VV (2005). Gerontological aspects of genome peptide regulation. Karger (2005)
- [9]Khavinson VKh et al AEDG peptide (epitalon) stimulates gene expression and protein synthesis during neurogenesis: possible epigenetic mechanism. Molecules (2012)
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