Antigonococcal Activity and Cytotoxicity Screening of Three Ziziphus Species Indigenous to South Africa

ABSTRACT Despite the extensive use of Ziziphus species in South African traditional medicine to treat various ailments, they remain poorly studied. Therefore, this study aimed to scientifically validate the ethnomedicinal use of Z. mucronata Willd., Z. rivularis Codd, and Z. zeyheriana Sond. in the treatment of gonorrhea. Their roots, stem bark, and leaves were sequentially extracted using five different solvents. The extracts were evaluated against Neisseria gonorrhoeae using the broth microdilution assay and cytotoxicity in rat skeletal (L6) myoblast cell lines. Of the 48 successive extracts evaluated, 12.5% exhibited high antigonococcal activity (MIC < 1 mg/mL), 33.3% showed moderate activity (MIC 1–6.25 mg/mL), and 54.1% were inactive (MIC > 6.25 mg/mL). Furthermore, the extracts displayed low cytotoxicity profiles, with 81% exhibiting no cytotoxicity (CC 50 > 0.05 mg/mL) and the remaining 19% cytotoxic (CC 50 < 0.05 mg/mL). Phytoconstituents tentatively identified and putatively attributed to the observed antigonococcal activity were n ‐hexadecanoic acid, phytol, and betulin. These have not been previously studied against N. gonorrhoeae ; further bioactivity screening in both in vivo and in vitro models is still needed to confirm their antigonococcal activity. Future research should focus on isolating phytoconstituents and testing the antigonococcal activity in vitro and in vivo.