Translational Research Initiative: Hidradenitis Suppurativa
The Role of Asymmetric Multi-JAK/TYK2 Inhibitors via Plant-Derived Natural Nanoparticles
1. Project Abstract
Hidradenitis Suppurativa (HS) is a severe, chronic autoinflammatory skin disease characterized by follicular hyperkeratosis and an aberrant immune loop mediated by the IL-23/Th17 axis and TNF-α. Current synthetic biological treatments present major limitations related to high costs and systemic adverse effects.
Our Hypothesis: Complex nutraceutical formulas (Imuniplant and Polenoderm) contain nanostructured fractions of plant origin (phyto-exosomes) capable of optimal systemic delivery. It is hypothesized that these compounds exert an asymmetric, reversible, and competitive inhibition on the intracellular JAK1/TYK2 pathways, mimicking the behavior of next-generation synthetic inhibitors, thereby inducing an epigenetic reset of skin tissue and a restoration of the microbiomes.
2. Cellular Mechanism & Correlation with Hurley Stages
The clinical progression of the disease is directly dictated by the intensity of the cytokine cascade registered in the deep dermis:
| Hurley Stage | Visible Clinical Manifestation | Subcutaneous Immune Process (The Molecular Driver) |
|---|---|---|
| Stage I | Single or multiple isolated abscesses, without sinus tracts (tunnels) or cicatrization. | Rupture of the follicular wall. The release of keratin into the dermis activates the NLRP3 inflammasome and local macrophages. Massive amounts of IL-1β and TNF-α are secreted, recruiting waves of neutrophils that form pus. |
| Stage II | Recurrent abscesses, sinus tracts (tunnels under the skin), and indurated fibrous scars. | Chronicization of the immune response through the activation of the Th17 pathway (IL-23 / IL-17). Cytokines stimulate matrix metalloproteinases (MMP-2, MMP-9) that dissolve collagen, creating cavities that are aberrantly lined by migrating epithelial cells. |
| Stage III | Confluent plaques, a labyrinth of interconnected tunnels, and continuous abscesses across an entire anatomical region. | Autonomous cytokine storm. Massive mixed cellular infiltrate (T cells, B cells, macrophages, and neutrophils). Total loss of normal dermal architecture, replaced by chaotic neoangiogenesis and rigid scar fibrosis. |
3. Asymmetric Immunomodulation via Multi-JAK/TYK2
Avant-garde allopathic medicine develops synthetic small molecules (e.g., brepocitinib) to block intracellular cytokine signaling through JAK pathways. Our project aims to demonstrate that the phyto-complexes in Imuniplant and Polenoderm achieve this effect naturally and asymmetrically:
- Through TYK2 inhibition: Signaling for IL-23 and Type I Interferons is blocked. Without IL-23, dendritic cells can no longer differentiate and sustain Th17 lymphocytes, cutting off IL-17 production directly at the source.
- Through JAK1 inhibition: The cellular response to IL-6 and IFN-γ is halted, dramatically reducing the alarm signals transmitted to macrophages and neutrophils.
4. Macrophage M1 → M2 Polarization (Post-Operative Solution in Hurley III)
A major novelty of this project is the approach to Hurley Stage III patients who have undergone wide surgical excisions. Surgery removes the anatomical defect, but not the underlying systemic disease. This is where the regenerative properties of our products intervene:
Post-operative wounds remain stuck in a destructive phase due to hyperactive M1 macrophages, which continuously secrete TNF-α, IL-6, and matrix metalloproteinases (MMPs), preventing standard wound closure.
Natural nanoparticles (phyto-exosomes) from our formulas block the JAK1/TYK2 pathways, disarming the aggressive profile of M1 macrophages.
Macrophages are reprogrammed into the anti-inflammatory M2 phenotype, starting to pump Interleukin 10 (IL-10) and TGF-β (Transforming Growth Factor).
TGF-β signals local fibroblasts to deposit newly organized collagen, while VEGF stimulates healthy neoangiogenesis. Wounds close rapidly, cleanly, and recurrences on the surgical graft margins are actively prevented.
5. Research Project Structure & Phases
To transform the clinical cases successfully resolved by Deniplant into universally recognized scientific evidence, the project is structured on three rigorous pillars:
Phase I: Nanotechnological Characterization
Isolation and visualization via electron microscopy of nanovesicles (phyto-exosomes) from Imuniplant and Polenoderm extracts, followed by their chemical fingerprinting via HPLC-MS (High-Performance Liquid Chromatography).
Phase II: Validation of the Immune Mechanism (In Vitro & Ex Vivo)
Testing fractions on stimulated human immune cell cultures (PBMCs) to measure the degree of inhibition of JAK1/TYK2 protein phosphorylation and the decrease of cytokines in the supernatant.
Phase III: Clinical and Epigenetic Monitoring
A pilot study on a patient cohort (Hurley I, II, and Hurley III post-operative). Inflammatory blood markers (CRP, ESR, cytokine panel) and changes in the gut/skin microbiome (16S rRNA sequencing) induced by oral treatment combined with epigenetic guidelines (the Deniplant diet) will be analyzed dynamically over time (varying from 4 to 12+ months based on disease chronicity).
Join Our Initiative & Contact Us
The Deniplant Research Center proposes this translational research project in a partnership framework to academic institutions, faculties of medicine, and advanced immunology laboratories in the United Kingdom (UK) and international spaces, where integrative medicine benefits from top-tier technological platforms.
Whether you are a medical researcher interested in collaboration or a patient wishing to inquire about entering our program,Please send an email to deniplant@gmail.com.