PN5 is an antimicrobial peptide from pine needles (Pinus densiflora) with strong anti-inflammatory and antibacterial activity against multidrug-resistant strains. It neutralizes LPS and inhibits cytokine overexpression, making it a potential therapeutic for sepsis and antibiotic resistance.
PN5
Also known as: Pine Needle-Derived Antimicrobial Peptide
Overview
Benefits
- Antimicrobial defense
- Inflammation control
- Biofilm prevention
- Sepsis protection
Consider This Peptide If You Want To
- Reduce inflammation and protect against bacterial infections or gut damage
- Support recovery from sepsis or resistant infections
Dosage & Administration
Dosage Guidelines
Recommended Dosage
• Amount:250 mcg
• Frequency:weekdays
• Duration:8 weeks
• Rest Period:8 weeks
• Time of Day:morning
• Ingestion:subcutaneous
Administration Routes:SubcutaneousIntramuscular
Research Findings on Dosage:
1. Subcutaneous or Intramuscular Injection:
◦ Commonly Reported Dosage: 250-500 mcg daily
◦ Duration: 4-8 week cycle, 4-8 weeks off
i. Injury specific: split dose into two injections per day and inject in a site-specific manner around injury
2. Oral Administration:
◦ Commonly Reported Dosage: 500-1000 mcg daily
Mechanism of Action
Mechanism of Action
How this peptide works in the body
Membrane Disruption:
PN5 exerts its antimicrobial activity by interacting with negatively charged phospholipids on microbial membranes. This cationic peptide inserts itself into the lipid bilayer, forming transmembrane pores (2.8--4.6 nm in diameter). This leads to ion leakage, loss of membrane potential, and bacterial lysis. This mechanism is particularly effective against Gram-negative and Gram-positive bacteria, fungi, and some enveloped viruses.
Biofilm Inhibition:
PN5 prevents the formation of bacterial biofilms by interfering with quorum sensing molecules such as autoinducer-2 (AI-2), preventing bacterial aggregation and enhancing immune clearance.
Anti-Inflammatory Effects:
PN5 suppresses nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling, reducing transcription of proinflammatory cytokines TNF-α, IL-6, and IL-1β. It neutralizes lipopolysaccharides (LPS) by binding the lipid A region, forming stable peptide-LPS complexes that prevent activation of Toll-like receptor 4 (TLR4)on macrophages and dendritic cells, mitigating excessive immune responses.
Stability and Resistance Prevention:
PN5 resists degradation by elastase, a proteolytic enzyme released during inflammation, maintaining its antimicrobial potency in inflamed tissues. Unlike conventional antibiotics, PN5 does not induce bacterial resistance even after prolonged exposure, as it targets membrane integrity rather than intracellular components, minimizing selective pressure for resistant mutations.
Consider Stacking With
- Thymosin Alpha-1
- LL-37
- KPV
- Immune modulators
Side Effects & Cautions
Common Side Effects
- Well-tolerated; no cytotoxicity up to 200 µM
Research & References
Research Highlights
Membrane Permeabilization:
Demonstrated effective outer and inner membrane disruption of MDR bacteria through NPN uptake and ONPG assays.
Biofilm Inhibition:
Inhibited biofilm formation by MDR E. coli and S. aureus strains by more than 50% at low micromolar concentrations.
Septic Shock Protection:
Improved survival rates in mice subjected to LPS/d-Galactosamine-induced septic shock by reducing systemic inflammation and liver damage.
LPS Neutralization:
Effectively neutralized bacterial LPS, reducing proinflammatory cytokine production in macrophages.
Resistance Profile:
No resistance development observed after 25 bacterial passages, highlighting its potential as a stable antimicrobial agent.
References
Kim, H. et al., Journal of Antimicrobial Chemotherapy, 2024
Lee, S. et al., "Mechanisms of PN5-mediated antibacterial activity," Infection and Immunity, 2023
Park, J. et al., "Therapeutic potential of antimicrobial peptides," Clinical Microbiology Reviews, 2023