Side-by-side · Research reference

HumaninvsPancragen

Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.

AAnimal-StrongHUMAN-REVIEWED14/52 cited

BAnimal-StrongHUMAN-REVIEWED23/39 cited

Humanin

Mitochondrial-Derived Peptide · Cytoprotective

24-AAPeptide lengthZhu 2022

mtDNAEncoded originZhu 2022 Shahzaib 2026

Bax/BimPrimary targetZhu 2022 Morris 2021

SQ · Experimental

Pancragen

Bioregulatory Tetrapeptide · Khavinson School

50 μgPrimate doseGoncharova 2014

10 daysTreatment cycleGoncharova 2015

3+ weeksEffect persistenceGoncharova 2014

IM · 10-day cycleGoncharova 2014

01Mechanism of Action

Parameter

Humanin

Pancragen

Primary target

Intracellular: Bax, Bim, tBid (pro-apoptotic Bcl-2 family). Extracellular: FPRL1/2 G-protein-coupled receptorsZhu 2022 Lue 2021

Pancreatic acinar and islet cell differentiation pathwaysKhavinson 2013

Pathway

Humanin binds Bax/Bim → inhibits mitochondrial outer membrane permeabilization (MOMP) → blocks cytochrome c release → prevents caspase activation → cell survival

Transcription factor activation → Pdx1/Pax6/Pax4/Ptf1a/Foxa2/NKx2.2 upregulation → Cell differentiationKhavinson 2013

Downstream effect

Suppression of apoptosis, mitochondrial stabilization, reduced oxidative stress, preservation of germ cells and neurons under stressZhu 2022 Lue 2021 Velentza 2024

Enhanced pancreatic beta-cell function, normalized insulin/C-peptide dynamics, improved glucose clearanceGoncharova 2014

Feedback intact?

Not applicable — peptide acts as anti-apoptotic signal, not hormonal axis

Yes — preserves physiological glucose-insulin response

Origin

Encoded by short open reading frame in mitochondrial 16S rRNA gene (MTRNR2). 24-28 amino acids. 13 homologous variants (MTRNR2L1-L13) identified.Zhu 2022 Shahzaib 2026

Synthetic tetrapeptide derived from pancreatic tissue extracts (Khavinson bioregulator methodology)

Antibody development

Not reported in animal models

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02Dosage Protocols

Parameter

Humanin

Pancragen

Standard experimental dose (HNG)

4 mg/kg IP (rat)

Most common dose in rodent models.

—

Ex vivo bone culture

1 µg/mL

Protective against venetoclax-induced bone growth retardation.

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Frequency

Daily (IP)

Once daily for 10 daysGoncharova 2014

Duration

8–12 weeks in animal studies

—

Evidence basis

Animal models (rat, mouse)Huang 2025 El 2022 Velentza 2024

Non-human primate RCT, in vitro cell cultureGoncharova 2015 Khavinson 2013

Human data

None — no clinical trials reported

—

Analog (HNG)

Gly[14]-humanin — more potent variant

Substitution at position 14 enhances cytoprotective activity.

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Primate dose (rhesus macaque)

—

50 μg / animal / dayGoncharova 2014

20–25-year-old females, 10-day IM protocol.

Effective concentration (in vitro)

—

0.05 ng/mLZakutskiĭ 2006

Organotypic tissue culture, both young and aged rat explants.

Route

—

IntramuscularGoncharova 2015

Treatment cycle

—

10-day course, effects persist 3+ weeks post-withdrawalGoncharova 2014

Diabetes model

—

STZ-induced diabetes (rat)

Evaluated via metabolic markers characterizing apoptosis.

03Metabolic / Fat Loss Evidence

Parameter

Humanin

Pancragen

Direct fat loss evidence

None

—

Mechanism overlap

Mitochondrial health may indirectly influence metabolic efficiency, but no quantified effect

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04Side Effects & Safety

Parameter

Humanin

Pancragen

Animal model safety

Well-tolerated in rat and mouse studies at 4 mg/kg for 8–12 weeks

—

Human safety data

None — no clinical trials

No published human trials; clinical use limited to Russian gerontology protocols

Theoretical fibrillation risk

Induces amyloid-like fibrillation of Bax/BID. Long-term sequelae unknown.

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Injection site reaction

Not reported in animal studies (IP route)

—

Reproductive safety

Protective in POI model (cyclophosphamide-induced), no adverse effects on fertility notedHuang 2025

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Reported adverse events

—

None documented in primate studies

Tolerability

—

Well-tolerated in aged rhesus monkeys (n=9)Goncharova 2015

Absolute Contraindications

Humanin

·Unknown — no human data

Pancragen

—

Relative Contraindications

Humanin

·Active malignancy (theoretical risk of anti-apoptotic effect on tumour cells)

Pancragen

·Active pancreatic malignancy (proliferation marker upregulation)

05Administration Protocol

Parameter

Humanin

Pancragen

1. Route (experimental)

Intraperitoneal (IP) in animal models. Subcutaneous route untested. No human protocols exist.

Lyophilised tetrapeptide reconstituted in sterile saline or water per manufacturer protocol. Concentration not specified in literature.

2. Reconstitution

Synthetic peptide reconstituted in sterile saline or PBS. No commercial formulation available.

Intramuscular injection. Primate studies used daily IM dosing for 10 consecutive days.Goncharova 2015

3. Timing

Daily administration in animal studies. Optimal timing not characterized.

No specific timing constraints documented. Administered once daily in primate protocols.

4. Storage

Lyophilised powder: -20 °C. Reconstituted: 4 °C, use within 7 days. Avoid freeze-thaw cycles.

10-day treatment course. Restorative effects on pancreatic function persist for at least 3 weeks post-discontinuation.Goncharova 2014

5. Human use

No FDA approval, no IND, no clinical trials. Experimental research tool only.

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06Stack Synergy

Humanin

+ MOTS-c

Multi-pathway

View MOTS-c →

Both are mitochondrial-derived peptides. MOTS-c enhances metabolic efficiency and insulin sensitivity via AMPK activation, while humanin prevents mitochondrial apoptosis. Combined, they address mitochondrial function (MOTS-c) and survival signaling (humanin), supporting cellular resilience under metabolic and oxidative stress.

Humanin: 4 mg/kg IP · daily (animal model)
MOTS-c: 5 mg/kg IP · daily (animal model)
Frequency: Once daily
Primary benefit: Mitochondrial health, metabolic efficiency, anti-apoptotic signaling

Pancragen

— no documented stacks