In vitro and in silico assessment of anti-arthritic potential of a polyherbal oil-in-water emulsion formulated with Piper betle L. and Zingiber officinale essential oils

Arthritis is a chronic inflammatory joint disease that requires safer therapeutic alternatives to prolonged use of synthetic drugs. The present study formulated and evaluated an oral oil-in-water emulsion containing a methanolic extract of Piper betle leaves and ginger essential oil for antioxidant and anti-arthritic activity. Preliminary phytochemical screening confirmed the presence of flavonoids and phenolic compounds. The total flavonoid and phenolic contents were 132 μg quercetin equivalents/g and 66 μg gallic acid equivalents/g of extract, respectively. Among the prepared formulations, formulation F3 exhibited suitable physicochemical characteristics, and maximum drug release of 96% at 180 min. In vitro antioxidant evaluation using the hydrogen peroxide scavenging assay demonstrated concentration-dependent activity, with half-maximal inhibitory concentration values of 130 μg/mL for formulation F3 and 145 μg/mL for the extract. Anti-arthritic activity assessed by egg albumin denaturation and hyaluronidase inhibition assays showed greater inhibition by formulation F3 (IC₅₀ 158 μg/mL and 171 μg/mL, respectively) compared with the extract and comparable activity to diclofenac sodium. Molecular docking studies revealed favourable binding of selected phytoconstituents toward the bradykinin B1 receptor, with binding energies up to -7.6 kcal/mol. These findings indicated that the polyherbal emulsion enhanced the biological activity of the extract and may serve as a potential natural anti-arthritic formulation. Further in vivo and clinical investigations are required to confirm its therapeutic applicability.