Bronchogen
Also known as: AEDL, ADEL, Lung bioregulator, Ala-Glu-Asp-Leu, Ala-Asp-Glu-Leu
Summary
Bronchogen is a synthetic tetrapeptide bioregulator (Ala-Glu-Asp-Leu/AEDL) developed by Vladimir Khavinson for respiratory system support. This short peptide interacts directly with DNA and histone proteins to regulate gene expression in bronchial epithelium, promoting differentiation and functional activity of lung cells. Research demonstrates its ability to stabilize DNA, reduce inflammation, restore epithelial integrity, and enhance surfactant production in animal models of chronic obstructive pulmonary disease (COPD) and lung injury.
Potential Benefits
Respiratory Function Support
Bronchogen regulates the expression of genes involved in bronchial epithelium differentiation including NKX2-1, SCGB1A1, SCGB3A2, FOXA1, and FOXA2 [1]. The peptide activates expression of MUC4, MUC5AC, and SFTPA1 genes, which are critical for mucus production and surfactant function [1]. In rat models of COPD, administration of tetrapeptide Bronchogen for 1 month eliminated symptoms of remodeling including goblet cell hyperplasia, squamous metaplasia, lymphocytic infiltration and emphysema, with restoration of ciliated cells [2].
Anti-Inflammatory Effects
Following peptide treatment in COPD models, decreased activity of neutrophilic inflammation was observed with normalization of cellular composition and profile of pro-inflammatory cytokines and enzymes in the bronchoalveolar space [3]. The therapy reduced inflammatory markers and enhanced secretory immunoglobulin A production, indicating normalized bronchial epithelium function [2]. Bronchogen enhanced alveolar macrophage activity, reduced inflammatory responses, and accelerated tissue repair mechanisms [4].
DNA Stabilization and Epigenetic Modulation
Differential scanning microcalorimetry demonstrated that Bronchogen increases DNA melting temperature by approximately 3.1°C, indicating DNA-stabilizing effects [5]. The peptide binds to linker histone H1 and core histone H3, specifically targeting the N-terminal lysine residue of H1 and lysine residue at position 36 of the H3 C terminus [6]. These interactions loosen tightly packed chromatin structure, creating transcriptionally active euchromatin and reducing condensed chromatin domains from 45% to 25% in experimental models [6].
Cellular Regeneration and Geroprotection
AEDL peptide proved to be an efficient agent stimulating cell renewal processes and enhancement of functional activity of bronchial epithelial cells [1]. The peptide regulates synthesis of proteins Ki67, Mcl-1, p53, CD79, and NOS-3 in cultures of human bronchial epithelial cells, demonstrating ability to modulate proliferation and apoptosis markers [1]. Short peptides can penetrate into the nuclei and nucleoli of cells and interact with DNA to regulate gene expression, providing a mechanism for tissue-specific regeneration [7].
Protection Against Oxidative Stress
AEDL decreases hydrogen peroxide (H2O2) content by almost 1.5 times while increasing glutathione (GSH) content by 3.24 times, indicating active participation in neutralizing excess reactive oxygen species [8]. The peptide increases expression of MnSOD and Cu/ZnSOD genes, accompanied by increased total superoxide dismutase (SOD) activity [8]. Under salt stress conditions, GSH content remained increased by 2.03 times compared to control, demonstrating sustained antioxidant protection [9].
Safety Information
Clinical Safety Profile
Peptide bioregulators, including Bronchogen, have demonstrated a favorable safety profile with over 40 years of clinical track record [10]. These compounds have been tested for toxicity, mutagenicity, allergenicity, and long-term effects, demonstrating a very high safety margin [10]. The tetrapeptide Ala-Glu-Asp-Leu was experimentally proved to be non-toxic [4].
Absence of Adverse Effects
Peptide bioregulators have no side effects apart from possible individual intolerance to capsule components (gelatin shell or excipients) [10]. The absence of side effects is explained by their mechanism of action - they do not start any chemical reactions that are not characteristic of the organism, but rather adjust and activate natural physiological processes [10]. Acute toxicity tests with doses 5000 times higher than normal showed no serious reactions, and long-term administration of 100 to 1000 times regular doses revealed no side effects in animals [11].
Regulatory Status
Bronchogen is protected by European patent EP1758922A1 and US patent 7,625,870 for use in restoring respiratory organ function [4]. The peptide has been approved for use in Russia and other countries as a dietary supplement, though it is not FDA-approved in the United States. Research applications include acute bacterial lung inflammation, chronic fibrosis inflammatory processes, and hyperoxic injury [4].
Contraindications and Precautions
No specific contraindications have been identified in the reviewed literature beyond potential individual intolerance to formulation components [10]. As with any bioregulator peptide, consultation with a healthcare professional is advised before use, particularly for individuals with pre-existing respiratory conditions or those taking other medications. Long-term safety data in humans is limited compared to animal studies.
Dosing Considerations
Typical dosing in research models involved administration over 1-month periods, with normalization of bronchial epithelium observed within this timeframe [2][3]. The peptide demonstrates tissue-specific effects on bronchial epithelium when administered orally, suggesting targeted action on respiratory tissues [1]. Optimal human dosing protocols have not been extensively characterized in peer-reviewed literature.