Pharmacological Insights into Capparis spinosa L.: Comparative Phytochemical Profiling and In Vitro Evaluation of Leaf and Stem Extracts

Capparis spinosa L. is a medicinal plant with diverse pharmacological potential; however, comparative characterization of the phytochemical profiles and multiple biological activities of its leaves and stems remains limited, particularly for plants collected in Saudi Arabia. This study provides an integrated comparison of methanolic leaf (CSLE) and stem (CSSE) extracts, combining volatile and semi-volatile GC-MS profiling with antioxidant, antibacterial, enzyme-inhibitory, cytotoxicity, and apoptosis-associated gene-expression analyses. CSLE exhibited higher extraction yield (13.31 ± 2.14%), total phenolic content (125.15 ± 1.21 mg GAE/g), and total flavonoid content (78.13 ± 1.14 mg QE/g) than CSSE. GC–MS tentatively identified 43 constituents in CSLE and 28 in CSSE, with differences in their relative GC-MS peak-area profiles. In the DPPH assay, CSLE showed stronger antioxidant activity, with DPPH and ABTS IC50 values of 129.69 µg/mL (95% CI: 96.52–145.28) and 47.25 µg/mL (95% CI: 45.46–51.89), respectively, compared with 162.45 µg/mL (95% CI: 157.42–172.21) and 68.46 µg/mL (95% CI: 64.70–72.12) for CSSE. CSLE also exhibited greater antibacterial activity (MIC = 7.81–62.50 µg/mL) and α-glucosidase inhibition (IC50 93.62 µg/mL (95% CI: 70.46–124.00) versus1 22.44 µg/mL (95% CI: 88.55–177.00) for CSSE). Both extracts inhibited α-amylase and reduced MCF-7 and HepG2 cell viability and were associated with changes in apoptosis-related gene expression; however, apoptosis was not functionally confirmed. The novelty of this study lies in its comprehensive comparison of the biochemistry of a Saudi C. spinosa L. plant accession using volatile/semi-volatile GC-MS analysis, TPC/TFC, antioxidant, six bacterial strains, two digestive enzyme inhibition, cytotoxicity, and apoptosis gene expression assessments all within a single experimental set-up; however, it does not claim to be the first leaf-stem comparison. These findings provide a basis for further investigation of their bioactive constituents and mechanisms of action.