Introduction: Medicinal plants remain a promising reservoir of bioactive compounds with therapeutic potential against chronic and infectious diseases. Peganum harmala L. (Zygophyllaceae), commonly known as Syrian rue, is widely used in traditional medicine for its antitumor, antimicrobial, and anti-inflammatory properties, primarily due to its rich alkaloid profile (harmine, harmaline, and β-carbolines). However, systematic pharmacological validation of its bioactivity against contemporary health challenges is still limited.
Methods: Ethanolic extracts of P. harmala seeds were prepared via Soxhlet extraction and subjected to GC–MS analysis for phytochemical profiling. In vitro antioxidant potential was assessed using DPPH and FRAP assays, while antibacterial efficacy was evaluated against multidrug-resistant (MDR) strains of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa using agar well diffusion and MIC determination. Anti-inflammatory activity was examined via protein denaturation and membrane stabilization assays. Cytotoxicity was analyzed on HepG2 and MCF-7 cell lines using MTT assays.
Results: GC–MS revealed the presence of 22 major phytoconstituents, including harmine, harmaline, vasicine, and quinazoline derivatives. The extract demonstrated strong radical scavenging activity (IC₅₀ = 38.6 µg/mL) and ferric reducing power (420 µmol Fe²⁺/g extract). Potent antibacterial activity was observed with inhibition zones up to 22 mm against MDR S. aureus, with MIC values as low as 125 µg/mL. The extract significantly reduced protein denaturation (67%) and stabilized red blood cell membranes (71%), suggesting robust anti-inflammatory effects. MTT assays revealed selective cytotoxicity, with IC₅₀ values of 48 µg/mL for HepG2 and 62 µg/mL for MCF-7, while sparing normal fibroblast cells.
Conclusion: Peganum harmala seed extract represents a pharmacologically rich candidate for drug discovery pipelines targeting oxidative stress, inflammation, antimicrobial resistance, and cancer. Further in vivo validation and mechanistic studies are warranted to translate its traditional use into modern therapeutic applications.
