NEXT-GENERATION PORTFOLIO OF ASYMMETRIC MULTI-JAK/TYK2 INHIBITORS WITH NATURAL NANOPARTICLES

NEXT-GENERATION PORTFOLIO OF ASYMMETRIC MULTI-JAK/TYK2 INHIBITORS WITH NATURAL NANOPARTICLES

Major Gheorghe GIURGIU¹, Prof dr med Manole COJOCARU^2,3

¹Deniplant-Aide Sante Medical Center, Biomedicine, Bucharest, Romania

deniplant@gmail.com; Telephone: +40 744 827 881

https://orcid.org/0000-0002-5449-2712

²Academy of Romanian Scientists, 3 Ilfov Street, Bucharest, Romania

³Titu Maiorescu University, Faculty of Medicine, Bucharest, 031593 Bucharest, Romania

cojocaru.manole@gmail.com; Telephone: +40 723 326 663
https://orcid.org/0000-0002-7192-7490

Correspondence*:deniplant@gmail.com

ABSTRACT

Context: Conventional allopathic immunosuppressive treatments (such as synthetic „Jakinibs”) used for autoimmune, metabolic, and neuroinflammatory conditions exhibit severe cytotoxicity due to the non-selective blockade of JAK2/JAK3 pathways. Modern botanical nanomedicine offers an eco-friendly and biocompatible alternative. It employs bionanomaterials and purified extracts capable of achieving highly precise physiological modulation. This innovation leverages the ability of complex phytochemical matrices to act as natural allosteric (asymmetric) inhibitors, selectively targeting only the hyperactive JAK1/TYK2 axes while leaving the host’s antiviral immunity intact.

Objectives: Development of a portfolio of high-purity, lyophilized bionanoproducts and nutraceuticals (the Deniplant®, Neuropolen, and Polenoplasmin range). Evaluation of the capacity of these natural nanoparticles to asymmetrically inhibit JAK1/TYK2 intracellular signaling and the NF-κB cascade. Demonstration of the regulatory role played by the microbiome’s metabolism of these compounds in epigenetic reprogramming and the restoration of mitochondrial and cellular homeostasis.

Materials and methods: Native phytochemical formulations underwent a technological upgrade via advanced processing-purified extraction followed by lyophilization (freeze-drying) at sub-zero temperatures (-40°C) under absolute vacuum. This method preserves the intact three-dimensional spatial conformation of polyphenols, flavonoids, and phytosterols, resulting in a superporous structure and maximized bioaccessibility. The mechanism of action was evaluated through „in vivo” clinical observational studies (conducted over more than 35 years in human and veterinary medicine), involving the monitoring of serum and fecal biomarkers: microbiome genetic sequencing (16S rRNA), analysis of short-chain fatty acids (SCFAs-specifically butyrate), determination of zonulin levels, and monitoring of the expression of protective heat shock proteins (HSP70/HSP27) as well as the allosteric inhibitory protein SOCS3.

Results: At the intestinal level, the lyophilized bionanomaterials acted as selective prebiotics, correcting dysbiosis and stimulating massive butyrate production. This functioned as an epigenetic switch, inducing the synthesis of SOCS3, which blocks JAK1/TYK2 kinases via a geometric (allosteric) mechanism. In acute phases, megadosing demonstrated rapid activation of HSP70 and HSP27, halting neuronal apoptosis within the penumbra zone. Clinically, complete and long-lasting remission of lesions was achieved in autoimmune dermatological conditions (psoriasis-through the „capping” of the risk gene CARD14), alongside the restoration of electrical conductivity in cases of severe paralysis following stroke or spinal cord injury (translational neuro-regeneration along the gut-spinal cord axis).

Conclusion: The portfolio of nutraceuticals and natural nanoparticles processed via lyophilization represents the future of systemic and predictive medicine. By mastering and modulating human physiology from within-devoid of the chemical cytotoxicity associated with conventional drugs-it has been demonstrated that directing the host-microbiome axis can induce stable remissions in pathologies deemed incurable by allopathic medicine, thereby opening new frontiers in pharmaceutical nanobiomaterials.

Keywords: Asymmetric inhibitors, TYK2/JAK1, natural nanoparticles, lyophilization, gut microbiome, epigenetic reprogramming, bionanomaterials.nutraceutice, Deniplant, Neuropolen, Polenoplasmin

References

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