Phytosomal gel of Cassia alata leaf extract for experimental polyarthritis: enhanced anti-inflammatory activity and mechanistic insights from integrated in silico, in vitro, and in vivo studies

To develop a phytosomal gel of Cassia alata leaf extract (CAPE) and evaluate its anti-inflammatory efficacy in Complete Freund’s Adjuvant (CFA)-induced experimental polyarthritis. CAPE was obtained by hydroethanolic extraction (yield: 8.4%) and assessed for antioxidant activity using DPPH and ABTS assays. Phytosomes were prepared via phospholipid complexation and characterized for particle size, zeta potential, and entrapment efficiency. The optimized formulation was incorporated into a Carbopol gel (CAPE-PhyGel). Molecular docking was performed against caspase-8 (PDB ID: 4JJ7). In vivo efficacy was evaluated following topical administration by assessing body weight, joint diameter, motor coordination, hematological and biochemical parameters, and histopathology. CAPE exhibited antioxidant activity with IC50 values of 118.91 µg/mL (DPPH) and 121.29 µg/mL (ABTS). The phytosomal formulation showed a particle size of 1.35 μm, zeta potential of −25 mV, and maximum entrapment efficiency of 75.21%. CAPE-PhyGel (200 mg/kg) significantly improved body weight, reduced joint diameter, and enhanced motor coordination compared to disease control (p < 0.001). It also normalized RBC, WBC, Hb, ESR, and reduced CRP and SRF levels. Histopathology confirmed reduced synovial inflammation and cartilage damage. Docking studies showed favorable binding affinities (up to −6.54 kcal/mol). Phytosomal delivery enhances the anti-inflammatory efficacy of Cassia alata in experimental polyarthritis, supporting its potential as a topical therapeutic system.