Sahar AlMotwaa, Waad Al-Otaibi
These findings suggest that the examined phytochemicals may exhibit potential affinity toward RA-related molecular targets. As this is a preliminary computational investigation, the results should be interpreted with caution and warrant further computational and experimental studies to confirm their biological and therapeutic relevance.
BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease and one of the most prevalent complex inflammatory disorders. Capparis spinosa L. (C. spinosa) is recognized for its diverse medicinal properties. Traditionally, the plant has been employed to alleviateconditions such as paralysis, gastrointestinal infections, rheumatism, diabetes, anemia, pain, and eye infections. This study aimed to investigate the potential interactions and predicted pharmacological relevance of major compounds identified in the essential oil of C. spinosa leaves using computational approaches.
METHODS: Drug-likeness potential was determined using Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiling and molecular docking. Gas chromatography-tandem mass spectrometry (GC-MS) was used to characterize the chemical composition of the essential oil. Drug-likeness studies were performed with SwissADME, while molecular docking was conducted using PyRx and BIOVIA Discovery Studio.
RESULTS: Fourteen major compounds were computationally screened against RA-associated molecular targets to evaluate their potential ligand-target interactions and drug-likeness characteristics. Absorption, Distribution, Metabolism, and Excretion (ADME) and drug-likeness were evaluated according to Lipinski's "rule of five" to determine whether the compounds exhibited suitable pharmacokinetic properties, consistent with criteria for pharmaceutical development. Six major phytoconstituents, i.e., tau-cadinol (M1), diisobutyl phthalate (M5), (Z)-3-hexenyl benzoate (M7), farnesyl acetone (M8), dibutyl phthalate (M10), and 1-(4-tert-butylphenyl)propan-2-one (M12), identified via GC-MS were docked with tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), nitric oxide synthase (NOS), and cyclooxygenase-2 (COX-2). This is the first report describing an in silico screening of GC-MS-identified compounds from C. spinosa for their predicted pharmacological potential. Docking ligand scores for all ligands against the target proteins ranged from -4.7 to -8.0 kcal mol-1. Diisobutyl phthalate (M5) showed the most favorable binding energies against IL-1β and NOS, relative to the other compounds and co-crystallized ligands; meanwhile, tau-cadinol (M1) exhibited the highest binding energy for TNF-α. Six prevalent phytochemicals demonstrated highly favorable predicted docking affinities toward IL-6 and COX-2, with M10 showing the lowest docking energy values among the tested compounds under the applied computational conditions.
CONCLUSIONS: These findings suggest that the examined phytochemicals may exhibit potential affinity toward RA-related molecular targets. As this is a preliminary computational investigation, the results should be interpreted with caution and warrant further computational and experimental studies to confirm their biological and therapeutic relevance.