Natural Product-Based Therapeutic Potential of Fagonia arabica: Phytochemical Characterization and Biological Activities of Leaf and Seed Extracts

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Background/Objectives: The increasing global prevalence of chronic diseases has intensified the search for potential natural therapeutic agents. Fagonia arabica is a medicinal plant widely used in traditional medicine; however, comparative information on the phytochemical composition and biological activities of its leaves and seeds remains limited. To the best of our knowledge, this study represents the first comparative investigation of the phytochemical profiles and bioactivities of methanolic leaf (FALE) and seed (FASE) extracts of F. arabica collected from Riyadh, Saudi Arabia. Methods: Methanolic extracts were analyzed by gas chromatography–mass spectrometry (GC–MS), and their total phenolic content (TPC), total flavonoid content (TFC), antioxidant, antimicrobial, anticancer, and antidiabetic activities were evaluated using standard in vitro assays. Results: GC–MS analysis identified 60 and 68 compounds in FALE and FASE, respectively, with (9Z,12Z,15Z)-octadeca-9,12,15-trienoic acid, hexadecanoic acid, dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol, and (1R,3aR,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a,5a,5b,8,8,11a-Hexamethyl-1-(prop-1-en-2-yl)-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysen-9-ol as major constituents. FASE exhibited higher TPC and TFC values (104.13 mg GAE/g and 62.16 mg QE/g, respectively) than FALE. Both extracts demonstrated antioxidant activity, with FASE showing greater potency against DPPH and ABTS radicals (IC50 = 63.3 and 42.4 μg/mL, respectively). FASE also displayed broad-spectrum antimicrobial activity, particularly against Staphylococcus aureus (MIC = 7.81 μg/mL). Furthermore, FASE exhibited stronger concentration-dependent cytotoxicity against MCF-7 and HepG2 cells, with IC50 values of 106.8 and 89.5 μg/mL, respectively, compared with 112.5 and 103.1 μg/mL for FALE. Apoptosis induction in MCF-7 and HepG2 cells was associated with upregulation of caspase-3, caspase-8, caspase-9, and Bax, alongside downregulation of Bcl-2 and Bcl-xL. In addition, FASE exhibited potent α-amylase and α-glucosidase inhibitory activities (IC50 = 61.62 and 67.38 μg/mL, respectively), comparable to acarbose. Conclusions: These findings highlight F. arabica seed extract as a promising source of multifunctional bioactive compounds with potential pharmaceutical application.

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