Ovagen
Summary
Ovagen is a Khavinson-class tripeptide (Glu-Asp-Leu, EDL) sold as a liver and gastrointestinal bioregulator, but every PubMed-indexed primary research paper on EDL studies the kidney: rat models of cisplatin, gentamicin, and ischemia-reperfusion injury, plus renal cell culture aging work. No liver or GI primary study, no human trial, and no pharmacokinetic study has been published.
Also known as: EDL, Glu-Asp-Leu, T-35
Key Findings at a Glance
- • Ovagen (Glu-Asp-Leu) is marketed as a liver and gastrointestinal bioregulator, yet every PubMed-indexed primary research paper on the EDL tripeptide studies kidney endpoints.
- • In rat cisplatin, gentamicin, and ischemia-reperfusion kidney injury models, EDL normalized diuresis, creatinine handling, and glomerular filtration while reducing proteinuria.
- • In aging renal cell culture, EDL reduced the senescence markers p16, p21, and p53 and increased SIRT-6, with DNA minor-groove binding proposed as the mechanism.
- • No human study, pharmacokinetic measurement, or formal safety assessment of Ovagen has been published.
Ovagen Overview & Molecular Profile
Ovagen (Glu-Asp-Leu, coded EDL) is a synthetic tripeptide from the Khavinson short peptide bioregulator family. It is marketed in supplement channels as a liver and gastrointestinal bioregulator, yet every PubMed-indexed primary research paper on the EDL peptide studies kidney endpoints rather than liver or GI outcomes; the hepatoprotective framing traces to review-level and monograph citations from the originating group rather than to any primary experimental study. In rat models of cisplatin-induced acute renal failure, gentamicin-induced nephropathy, and renal ischemia-reperfusion injury, EDL normalized diuresis, creatinine handling, glomerular filtration rate, and sodium resorption while reducing proteinuria and lipid peroxidation. In aging renal cell cultures it reduced the senescence markers p16, p21, and p53 and increased SIRT-6, with DNA minor-groove binding proposed as the mechanism. All studies come from the Khavinson network and its Ukrainian collaborators, and no human study of any design has been published.
Mechanism of Action: Gene Expression & Epigenetic Regulation
The proposing groups attribute EDL's renal effects to direct peptide-DNA interaction rather than to a membrane receptor. Molecular modeling accompanying the renal cell culture work found the most energetically favorable complexes with d(ATATATATAT)2 sequences in the DNA minor groove, and the authors link this binding to altered expression of aging-marker genes including p16, p21, p53, and SIRT-6. A companion study identified the gelatinase MMP-14 as a specific gene-expression target of the EDL peptide, coded T-35 in that work, during in vitro aging of primary kidney cell cultures. The same network's systematic review places EDL within a class of short peptides proposed to penetrate cell nuclei and regulate transcription. No receptor-level target has been identified, and no structural-biology confirmation of the DNA-binding model exists for EDL.
Ovagen Pharmacokinetics: An Unstudied Tripeptide
No pharmacokinetic parameter has been published for the EDL tripeptide in any species. The three-residue peptide carries two acidic amino acids and is expected to be highly water soluble and rapidly cleared, but every specific claim about its absorption, distribution, metabolism, or excretion is inference rather than measurement.
What the Animal Studies Imply
- • Rat nephroprotection studies administered EDL around the time of kidney injury and observed functional renal effects, implying systemic exposure from parenteral dosing, but doses and plasma levels are not disclosed in the available English abstracts (PMID 28744634).
- • In cisplatin-induced acute renal failure, EDL normalized glomerular filtration rate and sodium handling, consistent with the peptide or its effects reaching renal tissue (PMID 26515176).
- • No oral bioavailability data exist, a notable gap because the product is marketed in supplement channels in oral forms.
The Measurement Gap
- • No half-life, clearance, volume of distribution, or bioavailability figure has been reported for EDL in any species.
- • The proposing group attributes EDL's effects on renal cell senescence markers to direct DNA minor-groove binding, a mechanism that would decouple effect duration from plasma presence (PMID 25946838).
- • Class-level reviews describe nuclear penetration of short peptides as the basis of their action, but compound-specific pharmacokinetics for EDL remain entirely uncharacterized (PMID 34834147).
Research-Observed Effects
Nephroprotection in Toxic Kidney Injury Models
Moderate ResearchThe EDL tripeptide produced nephroprotective effects across three mechanistically distinct rat models of acute kidney injury. In cisplatin-induced acute renal failure, EDL normalized diuresis, creatinine concentration and excretion, glomerular filtration rate, and absolute sodium resorption while reducing proteinuria. In gentamicin-induced nephropathy and ischemia-reperfusion injury, it prevented oliguria and retention azotemia, decreased proteinuria and sodium excretion, prevented critical declines in antioxidant enzyme activity, suppressed lipid peroxidation, and normalized energy supply to kidney cells. The consistency of benefit across toxic and ischemic models is the strongest experimental signal in the Ovagen literature, though every study comes from the same collaborating network and none was designed with safety endpoints.
Renal Cell Senescence Marker Modulation
Preliminary ResearchIn aging primary kidney cell cultures, EDL increased cell proliferation while decreasing expression of the senescence markers p16, p21, and p53 and increasing expression of SIRT-6, a sirtuin whose reduction the authors identify as one cause of cellular senescence. A companion study found that the kidney polypeptide complex and the AED tripeptide activated cell renewal markers during renal epithelium aging, while the EDL peptide, coded T-35 in that work, specifically targeted the gelatinase MMP-14, an extracellular matrix remodeling enzyme. These cell-culture findings ground the geroprotective framing of the peptide within the Khavinson research program, without any in vivo confirmation of anti-aging effects in kidney tissue.
Direct DNA Minor-Groove Interaction
Preliminary ResearchMolecular modeling published with the renal cell culture experiments constructed interaction models of EDL with DNA and found the most energetically favorable complexes with d(ATATATATAT)2 sequences in the minor groove. The authors propose that this direct peptide-DNA interaction drives the observed changes in expression of aging-marker genes in renal cells, placing EDL inside the broader Khavinson framework of short peptides as gene-expression regulators. The model is computational and has not been confirmed for EDL by structural methods such as crystallography or NMR, and no receptor-level target has been identified for the tripeptide.
Kidney Function in Aged Rats
Preliminary ResearchIn old rats, administration of the kidney polypeptide complex and the peptides AED and EDL increased diuresis by 1.2 to 1.4 times, increased distal sodium transport by 1.2 to 1.3 times, and raised sodium excretion, with the complex and AED additionally reducing urinary protein level and protein excretion by 1.5 to 2.8 times. The study positions EDL as a candidate geroprotector for age-related kidney function decline and motivates the prophylactic nephroprotection framing used by the research group. Doses are not disclosed in the English abstract, and the work has not been replicated outside the originating collaboration.
Safety & Tolerability
No dedicated safety, tolerability, or pharmacokinetic study has been published for the EDL tripeptide in any species. Rat nephroprotection studies report functional benefit without structured adverse-event assessment, which cannot be read as demonstrated safety. Marketing of Ovagen as a liver or gastrointestinal bioregulator is not supported by any PubMed-indexed primary research paper.
Human data: No human studies of any design have been published for Ovagen (EDL); all indexed evidence is rat in vivo work or rat and calf kidney cell culture experiments.
Regulatory status: Not approved for human use by any major regulatory agency; no verified pharmaceutical registration. Commercial supplement availability in some markets does not represent regulatory evaluation of safety or efficacy.
- PubMed 28744634
In rat gentamicin nephropathy and ischemia-reperfusion models, EDL prevented oliguria and azotemia and reduced proteinuria; no adverse effects were described, but the study was not designed to detect them.
Animal - PubMed 26515176
In cisplatin-induced acute renal failure in rats, EDL normalized diuresis, creatinine handling, and glomerular filtration rate; again, no structured toxicity endpoints were reported.
Animal - PubMed 25946838
In aging renal cell culture, EDL reduced p16, p21, and p53 expression and increased SIRT-6, with DNA minor-groove binding proposed as the mechanism; these are mechanistic cell findings, not safety data.
In-vitro - PubMed 34834147
The class framework asserts gene-expression modulation through direct peptide-DNA interaction; the long-term safety of sustained chromatin-level intervention has never been evaluated for EDL or any class member.
Theoretical
Research Protocol Doses Reported in Published Literature
Research Disclaimer: Doses reported below are from published preclinical research protocols. Ovagen is not approved by the US FDA for human use; regulatory status can differ in other countries, so see the regulatory status note in the safety section of this page. This information is provided for research reference only and does not constitute a dosing recommendation.
Rat studies administered the EDL peptide parenterally around the time of kidney injury; the available English abstracts do not disclose exact doses. No human dosing protocol exists, no pharmacokinetic study has been published, and no oral bioavailability data exist despite oral marketing in supplement channels.
All doses above are reported from published research protocols using laboratory subjects. Refer to the cited studies in the Research Studies section above for original source data.
Research Studies & References
Nephroprotective Effect of EDL Peptide at Acute Injury of Kidneys of Different Genesis
Zamorskii II, Shchudrova TS, Lin'kova NS, et al.
Bulletin of Experimental Biology and Medicine (2017)
This study tested the EDL peptide in two rat models of acute kidney injury: gentamicin-induced nephropathy and ischemia-reperfusion injury. EDL produced a nephroprotective effect in both models, preventing oliguria and retention azotemia, decreasing proteinuria and sodium excretion, preventing critical decreases in antioxidant enzyme activities, suppressing lipid peroxidation, and normalizing energy supply to kidney cells. The authors conclude that further study of EDL's nephroprotective properties across kidney pathologies is warranted. The work comes from Bukovinian State Medical University in collaboration with the St. Petersburg bioregulation group, and it reports no structured safety endpoints.
Peptides Restore Functional State of the Kidneys During Cisplatin-Induced Acute Renal Failure
Zamorskii II, Shchudrova TS, Lin'kova NS, et al.
Bulletin of Experimental Biology and Medicine (2015)
This rat study compared a polypeptide complex from kidney with the short peptides AED, EDL, and AEDG in cisplatin-induced acute renal failure. The AED peptide decreased urinary protein excretion and electrolyte concentration, while the kidney polypeptide complex and the EDL and AEDG peptides normalized diuresis, urine creatinine concentration and excretion, glomerular filtration rate, and absolute sodium resorption, and reduced proteinuria and urinary sodium and potassium concentrations. The authors describe the EDL peptide as producing a potent nephroprotective effect. The parallel testing of related sequences makes this a key structure-activity data point within the Khavinson renal peptide program.
Peptides regulate expression of signaling molecules in kidney cell cultures during in vitro aging
Khavinson VKh, Lin'kova NS, Polyakova VO, et al.
Bulletin of Experimental Biology and Medicine (2014)
This cell-culture study examined a calf kidney polypeptide complex and the short peptides T-31 (AED) and T-35 (EDL) in primary kidney cell cultures during in vitro aging, measuring markers of cell renewal (Ki-67, p53), extracellular matrix remodeling (MMP-14), and immune response (IL-8). The renal polypeptide complex and the T-31 peptide activated cell renewal processes during aging of the renal epithelium, while the gelatinase MMP-14 was identified as the specific target of the T-35 (EDL) peptide. The work assigns EDL a distinct molecular signature within the renal peptide program and links it to matrix remodeling rather than to the proliferation pathway affected by its sibling peptides.
Tripeptides slow down aging process in renal cell culture
Khavinson VKh, Tarnovskaia SI, Lin'kova NS, et al.
Advances in Gerontology (2014)
This study investigated the geroprotective mechanism of the AED and EDL tripeptides in aging renal cell culture. Both peptides increased cell proliferation, decreased expression of the aging markers p16, p21, and p53, and increased expression of SIRT-6 in young and aged renal cells, with the authors noting that reduced SIRT-6 synthesis is one cause of cell senescence. Based on the experimental data, the authors constructed models of peptide interaction with DNA sites and found that both peptides form their most energetically favorable complexes with d(ATATATATAT)2 sequences in the DNA minor groove, proposing this binding as the cause of the altered expression of aging-marker genes.
The influence of peptides on the morphofunctional state of old rats kidneys
Zamorskii II, Shchudrova TS, Zeleniuk VG, et al.
Advances in Gerontology (2018)
This in vivo study examined the kidney polypeptide complex and the peptides AED, EDL, and AEDG in old rats, motivated by the prevalence of kidney pathology in elderly populations. Administration of the complex and of AED and EDL increased diuresis by 1.2 to 1.4 times. The complex and AED reduced urine protein level and protein excretion by 1.5 to 2.8 times. The complex, AED, and EDL increased distal sodium transport by 1.2 to 1.3 times, and AED and EDL increased sodium excretion by 1.3 and 1.6 times respectively. The work frames short peptides as candidate geroprotective nephroprotectors for age-related kidney function decline.
Peptide Regulation of Gene Expression: A Systematic Review
Khavinson VK, Popovich IG, Linkova NS, et al.
Molecules (2021)
This systematic review from the St. Petersburg group synthesizes the evidence that short peptides of 2 to 7 amino acids regulate gene expression across species from plants to humans. It describes penetration of short peptides into cell nuclei and nucleoli and their interaction with nucleosomes, histone proteins, and single- and double-stranded DNA, with DNA-peptide sequence recognition proposed to affect replication, transcription, and reparation, and it reviews peptide effects on DNA methylation status. The review is the class-level framework document cited for the EDL peptide's proposed mechanism, and its table of peptide effects is the source to which Ovagen's hepatoprotective marketing claims trace, rather than to any primary liver experiment.
Frequently Asked Questions
What is Ovagen?
Ovagen is a synthetic tripeptide, Glu-Asp-Leu (EDL), from the Khavinson short peptide bioregulator family. It is marketed in supplement channels as a liver and gastrointestinal bioregulator, but the PubMed-indexed primary research on EDL concerns the kidney: rat models of cisplatin, gentamicin, and ischemia-reperfusion injury, plus renal cell culture aging studies. It is not approved as a drug in any country.
Is Ovagen really a liver peptide?
The commercial positioning says liver and GI, but the indexed experimental literature says kidney. PubMed searches surface no primary experimental paper on EDL for liver or gastrointestinal endpoints; the hepatoprotective framing traces to review-level and monograph citations from the originating group, including the class systematic review (PMID: 34834147), rather than to any primary liver study. The liver-directed tetrapeptide in the Khavinson literature is a different compound, Livagen (Lys-Glu-Asp-Ala).
What did the Ovagen kidney studies show?
In cisplatin-induced acute renal failure in rats, EDL normalized diuresis, creatinine handling, glomerular filtration rate, and sodium resorption while reducing proteinuria (PMID: 26515176). In gentamicin-induced nephropathy and ischemia-reperfusion injury, it prevented oliguria and retention azotemia, decreased proteinuria, preserved antioxidant enzyme activity, and suppressed lipid peroxidation (PMID: 28744634). All studies are from one collaborating network and none was designed to detect adverse effects.
Has Ovagen been studied in humans?
No. There is no human clinical trial, no human pharmacokinetic study, and no human observational report for the EDL tripeptide. The closest human-relevant data are rat renal cell culture experiments tracking senescence markers such as p16, p21, p53, and SIRT-6 (PMID: 25946838). Any human use reports circulating online are anecdotal.
Is Ovagen safe?
There is no safety evidence in either direction. No toxicology study, no pharmacokinetic characterization, and no structured adverse-event reporting exist for EDL. Related Khavinson short peptides have been administered to animals at various doses without reported toxicity, but class-level reassurance is not compound-specific safety data. Ovagen is an unapproved research compound.
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