ArticleNaunyn-Schmiedeberg's archives of pharmacology2026
β-Sitosterol-loaded leciplexes attenuate rheumatoid arthritis in rats by modulating JAK2/STAT3, NF-κB, and p38 MAPK signaling pathways.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent synovial hyperplasia, progressive osteoarticular destruction, and systemic inflammatory complications. β-Sitosterol (BSS), a plant-derived phytosterol, exhibits anti-inflammatory and antioxidant properties; however, its therapeutic utility is limited by poor aqueous solubility and low oral bioavailability. This study aimed to enhance the oral delivery of BSS using Leciplex nanocarriers (BSS-LPXs) and to investigate their effects on key inflammatory pathways in Complete Freund's Adjuvant (CFA)-induced RA in rats. BSS-LPXs were optimized using a Box-Behnken design to achieve optimal vesicle size, entrapment efficiency, and sustained drug release. Pharmacokinetic parameters were assessed following oral administration in rats. Anti-arthritic pharmacodynamics were evaluated via clinical arthritis scoring, serum cytokine levels (TNF-α, IL-6), oxidative stress markers (GSH, SOD, MDA), and histopathological examination. Mechanistic studies focused on the modulation of JAK2/STAT3, NF-κB, and p38 MAPK signaling pathways. Optimized BSS-LPXs had an average size of ~ 146 nm, 66% entrapment efficiency, and sustained release characteristics. Oral administration of BSS-LPXs significantly increased bioavailability by 3.8-fold compared to the conventional suspension (p < 0.05), with higher C
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