1. For centuries, medicinal and aromatic plants have served as a natural source of products for treating various human diseases (Christaki et al. 2012). These plants include a high concentration of...

This study aimed to investigate the phytochemical constituents, antimicrobial activity, and antioxidant effects of successive extracts of Ziziphora capitata L. aerial parts. UPLC-QTOF-MS/MS identified 79 phytoconstituents, including phenolic acids, alkaloids, flavonoids, and anthocyanins, as major phytoconstituents. Additionally, primary phytochemical investigations revealed the presence of terpenoids, steroids, flavonoids, alkaloids, tannins, and saponins in various plant fractions. The MICs of successive extracts were tested against a range of microorganisms, including gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis, Streptococcus mutants, Enterococcus faecalis, Methicillin-Resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis), gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhimurium, and Enterobacter cloacae), fungi (Aspergillus niger and Penicillium aurantiogriseum), and yeast (Candida albicans and Candida tropicalis), using the disk diffusion technique. The ethyl acetate and 95% ethanol extracts exhibited significant antibacterial activity against the tested microorganisms; however, the hexane fraction affected only P. aeruginosa. The effects of the CHCl₃ and H₂O fractions varied in their activities against most of the bacteria examined. Additionally, the AcOEt and 95% EtOH extracts exhibited significant antioxidant activity with IC₅₀ = 18.6 ± 0.97 and 30.4 ± 1.86 µg/mL, respectively, compared to that of ascorbic acid (IC₅₀ = 10.6 ± 0.8 µg/mL, reference drug). Antibacterial and antioxidant activities can be attributed to phytoconstituents, which were identified using UPLC-QTOF-MS/MS. Furthermore, docking simulations of the top ten phytochemicals of the 70% methanolic extract were carried out inside the active site of S. aureus DNA gyrase (PDB: 2XCT) and dihydropteroate synthase (DHPS) from S. pneumoniae (PDB: 2VEG) as bacterial targets and these compounds exhibited good binding modes with different types of interactions. Graphical Abstract

Ziziphora capitata L. and Ziziphora tenuior L., members of the Lamiaceae family are versatile plants known for their culinary and medicinal properties. This comprehensive review focuses on medicinal potential through an analysis of phytoconstituents, biological activities, and traditional medicinal uses. A literature review revealed that the extracts of Z. capitata L. and Z. tenuior L. contain significant flavonoid and phenolic content. Metabolite profiling identified flavonoids, phenolic acids, anthocyanins, coumarins, and other bioactive compounds, and essential oils (EOs) contain pulegone as a major constituent. Studies have shown that these plants have a remarkable ability to scavenge free radicals, which contributes to the reduction of oxidative stress in cells. Advanced techniques such as UPLC-QTOF-MS/MS, GC-FID, and GC–MS have been used to identify the compounds responsible for antioxidant, antibacterial, and cytotoxic activities, leading to the discovery of a wide range of flavonoids and phenolic acids. The cytotoxic activities of Z. capitata against HepG-2, MCF-7, HCT-116, A549, and PC3 cell lines were evaluated, indicating potential anticancer properties, in addition to antibacterial and antioxidant activities against bacterial strains extracts, and essential oil. Overall, this review underscores the medicinal significance of Ziziphora species, particularly their phytoconstituents, antioxidant, antimicrobial, anticancer, and immunostimulatory properties. These findings provide a basis for further investigation and potential development of Ziziphora-based therapeutics and nutraceuticals