Investigating the Therapeutic Potential of Sericin Nanofibers and Rice-Encapsulated Nanosericin for Psoriasis: Mechanistic Insights from a 3D Skin Model

Passanesh Sukphopetch,1 Pornanong Aramwit,2– 4 Onrapak Reamtong,5 Tipparat Thiangtrongjit,5 Tapanee Kanjanapruthipong,6 Watcharamat Muangkaew,1 Kanchana Kengkoom,7 Kamonpan Fongsodsri,6 Sumate Ampawong6 1Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Ratchathewi, Bangkok, 10400, Thailand; 2Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences and Center of Excellence in Bioactive Resources for Innovative Clinical Applications, Chulalongkorn University, Pathum Wan, Bangkok, 10330, Thailand; 3The Academy of Science, The Royal Society of Thailand, Dusit, Bangkok, 10330, Thailand; 4Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, 73000, Thailand; 5Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Ratchathewi, Bangkok, 10400, Thailand; 6Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Ratchathewi, Bangkok, 10400, Thailand; 7Independent Researcher, Thaweewatthana, Bangkok, 10170, ThailandCorrespondence: Sumate Ampawong, Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok, 10400, Thailand, Tel + 662 3549100, Fax + 662 6447938, Email [email protected]: Psoriasis, a chronic inflammatory skin disorder affecting 2– 3% of the global population, presents significant treatment challenges, including high recurrence, adverse effects, and socioeconomic burdens. This study explores the therapeutic potential of sericin-based nanofibers and rice-encapsulated nanosericin (ReS) as innovative treatments, aiming to address current limitations by enhancing drug delivery, stability, and efficacy, and providing a targeted approach to managing this complex condition.Methods: This study investigates the efficacy of sericin nanofibers and derivatives, including ReS, for psoriasis treatment using a 3D artificial human skin model. Comprehensive evaluations were conducted through histopathological, immunohistochemical, molecular, and proteomic analyses.Results: Results showed that desolvation with glutaraldehyde crosslinking produced stable nanofibrils, while desolvation without crosslinking yielded nanogranules; nanoforms demonstrated high biocompatibility and safety. Treatments with sericin, rice extract, nanosericin, and ReS alleviated psoriasis-induced histopathology, with downregulation of IL-1β, WNT, and β-defensin particularly in the ReS and rice extract groups, suggesting an immunomodulatory effect. Caspase-3 reduction was more pronounced in the sericin and nanosericin groups. Proteomic analysis revealed notable exosomal protein involvement, with sericin modulating cell death through the PAK-2p34 pathway and proteasome activity, while nanosericin enhanced glycolysis and gluconeogenesis via exosomal proteins. Both ReS and nanosericin activated antioxidant pathways, mediated by upregulation of TGF-β and Nrf-2, respectively, especially sericin-based treatment through the selenoamino acid metabolism pathway. ReS further reduced keratinocyte differentiation by targeting cornified envelope proteins, correlating with reduced WNT expression. Gene expression analysis confirmed anti-inflammatory effects and skin barrier restoration, as evidenced by decreased S100-family proteins and increased filaggrin, caspase-14, and involucrin.Conclusion: ReS and nanosericin show significant therapeutic potential for psoriasis by targeting immunomodulatory pathways, modulating keratinocyte activity, reducing oxidative stress, and enhancing skin barrier restoration. Future research should optimize scalability, assess long-term safety, and explore synergistic effects with existing therapies, while further investigating molecular mechanisms for targeted treatment advancements. Keywords: psoriasis, sericin, nanotherapeutics, rice extract, 3D skin model, proteomic

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