Ethnopharmacology, phytochemistry, and cytotoxic insights into Ziziphus species indigenous to South Africa

South Africa is home to five species of the genus Ziziphus Mill. (Rhamnaceae), of which only three, being Z. mucronata Willd., Z. rivularis Codd, and Z. zeyheriana Sond., are indigenous. Ethnomedicinally, they are known to treat various diseases, including malaria, sexually transmitted infections (STIs), diarrhea, tuberculosis (TB), and hypertension. This review examined the ethnobotanical, ethnomedicinal, ethnopharmacological, phytochemical, and cytotoxic properties of these three Ziziphus species. Published articles were retrieved from databases using the search terms “ Ziziphus mucronata," “ Ziziphus rivularis," and “ Ziziphus zeyheriana." The criteria for inclusion and exclusion were established in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 685 records were retrieved from ScienceDirect (533), Web of Science (112), and PubMed (40). After the initial screening, 152 articles related to the three indigenous Ziziphus species were selected and subsequently evaluated for eligibility, resulting in 94 eligible articles. Of the three Ziziphus species, Z. mucronata has been studied extensively, compared to Z. rivularis and Z. zeyheriana . Researchers have extensively investigated the in vitro biological activity and cytotoxicity of Z. mucronata , but in vivo studies remain significantly lacking. Furthermore, a small fraction of phytoconstituents have been isolated from Z. mucronata , while none have been isolated from Z. rivularis and Z. zeyheriana . This review has revealed a notable deficiency in research concerning the ethnopharmacology, phytochemistry, and cytotoxicity of Ziziphus species indigenous to South Africa. Identifying and addressing these deficiencies will enhance bioprospecting efforts aimed at discovering promising phytochemicals from indigenous plant species in South Africa.