Exosome mediated delivery of Epigallocatechin 3 gallate as a novel approach to alleviate psoriasis symptoms through cytokine and apoptotic pathway modulation

Abstract

Psoriasis is a chronic skin disorder with significant individual and societal impacts. Current therapies often lack efficacy, are costly, or cause side effects, necessitating new treatments. This study explores regenerative therapies-exosomes, mesenchymal stem cells (MSCs), epigallocatechin-3-gallate nanoparticles (EGN), and EGN-loaded exosomes (EGN-Exo)-in regulating psoriasis-related markers (IL-6, IL-4, Bcl-2, Bax, NF-κB, CDC25B). An imiquimod-induced psoriasis model in Wistar rats was used, with six groups: negative control, positive control, and treatments (MSCs, exosomes, EGN, EGN-Exo). After seven days, ELISA revealed EGN-Exo most effectively reduced pro-inflammatory IL-6 and pro-apoptotic Bax while increasing anti-inflammatory IL-4 and anti-apoptotic Bcl-2. EGN-Exo also significantly lowered NF-κB and CDC25B, demonstrating superior anti-inflammatory effects. Apoptosis profiling showed EGN-Exo reduced late apoptotic cells, highlighting cytoprotective abilities. EGN had a moderate effect, while MSCs and exosomes showed modest improvements. Histopathological and immunohistochemical analyses confirmed EGN-Exo's efficacy, notably reducing TGF-β expression. These findings suggest EGN-Exo combines EGCG's antioxidant and anti-inflammatory properties with exosomes' targeted delivery, offering a promising advanced therapy for psoriasis.