Chemical Profiling, Analgesic and Anti-Inflammatory Activities of Farsetia aegyptia and Zilla spinosa: Integrated In Vitro, In Vivo, and In Silico Studies

Abstract

Plants are a rich source of active metabolites that have been used to treat inflammation troubles. The current study aimed to identify the analgesic and anti-inflammatory compounds in <i>Farsetia aegyptia</i> and <i>Zilla spinosa</i> extracts. The anti-inflammatory activity was evaluated using the xylene-induced ear edema model in mice and the carrageenan-induced paw edema model in Wistar rats. Additionally, both central and peripheral analgesic effects were assessed in mice. The anti-lipoxygenase activity was examined through an in vitro enzyme inhibition assay. The phytochemical composition of the bioactive extracts was characterized using High-Resolution Liquid Chromatography-Mass Spectrometry (HR-LCMS). The aqueous extracts of both species exhibited the strongest anti-inflammatory activity. The <i>F. aegyptia</i> extract showed inhibition percentages of 51.82% at 6.25 mg/kg and 51.14% at 0.78 mg/kg, while the <i>Z. spinosa</i> extract yielded 65.05% inhibition at 12.5 mg/kg and 56.14% at 1.56 mg/kg in the paw and ear edema models, respectively. These extracts also demonstrated significant analgesic activity and inhibited lipoxygenase, with IC₅₀ values of 0.063 mg/mL for <i>F. aegyptia</i> and 0.072 mg/mL for <i>Z. spinosa</i>. HR-LCMS analysis revealed that the main constituent in Fa was malic acid (18.83%), while retronecine (19.03%) was the primary compound in <i>Z. spinosa</i>. Quercetin 3-[rhamnosyl-(1->2)-rhamnosyl-(1->6)-glucoside] was detected in both extracts with important proportions 7.87% in <i>F. aegyptia</i> and 8.29% in <i>Z. spinosa</i> and displayed the best docking score of -9.2 kcal/mol against the 5-lipoxygenase receptor (PDB: 3V99) in molecular docking studies. Overall, these findings indicate that <i>F. aegyptia</i> and <i>Z. spinosa</i> have significant potential as sources of novel anti-inflammatory agents.