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Abstract Introduction Triple-negative breast cancer (TNBC) represents a significant global health crisis due to its resistance to conventional therapies and lack of specific molecular targets. This study explored the potential of Eriocephalus racemosus (E. racemosus) as an alternative treatment for TNBC. The cytotoxic properties and high-resolution respirometry mitochondrial activities of E. racemosus against the MDA-MB 231 TNBC cell line were evaluated. Methods Hexane solvent and bioactive fraction extractions of E. racemosus were performed, while mass spectrometry-based metabolite profiling was used to identify the phytochemical constituents of the extracts. The extracts were further tested against MDA-MB 231 TNBC cells to determine their cytotoxicity. The mode of cell death was determined using flow cytometry. The activities of caspases 3, 8, and 9 were assessed using a multiplex activity assay kit. Glycolytic activity and High-resolution respirometry measurements of mitochondrial function in the MDA-MB 231 cell line were conducted using the Seahorse XFp and Oroboros O2K. Results Metabolite profiling of E. racemosus plant crude extracts identified the presence of coumarins, flavonoids, sesquiterpenoids, triterpenoids, and unknown compounds. The extracts demonstrated promising cytotoxic activities, with a half maximal inhibitory concentration (IC50) of 12.84 µg/mL for the crude hexane extract and 15.49 µg/mL for the bioactive fraction. Further, the crude hexane and bioactive fraction extracts induced apoptosis in the MDA-MB-231 TNBC cells, like the reference drug cisplatin (17.44%, 17.26% and 20.25%, respectively) compared to untreated cells. Caspase 3 activities confirmed the induction of apoptosis in both cisplatin and the plant crude extracts, while caspase 8 and 9 activities confirmed the activation of both the intrinsic and extrinsic apoptosis pathways. Increased levels of glycolytic activity were observed in the hexane crude extract. High-resolution respiratory measurements showed elevated mitochondrial activities in all mitochondrial states except for complex-IV activity. Conclusion These findings support further exploration of E. racemosus as a potential therapeutic agent for TNBC, offering a promising avenue for the development of targeted treatments with minimal adverse effects.

Abstract Medicinal plants play a huge role in the treatment of various diseases in the Limpopo province (South Africa). Traditionally, concoctions used for treating tuberculosis and cancer are sometimes prepared from plant parts naturally occurring in the region, these include (but not limited to) Schotia brachypetala, Rauvolfia caffra, Schinus molle, Ziziphus mucronate, and Senna petersiana. In this study, the aim was to evaluate the potential antimycobacterial activity of the five medicinal plants against Mycobacterium smegmatis mc2155, Mycobacterium aurum A + , and Mycobacterium tuberculosis H37Rv, and cytotoxic activity against MDA-MB 231 triple-negative breast cancer cells. Phytochemical constituents present in R. caffra and S. molle were tentatively identified by LC-QTOF-MS/MS as these extracts showed antimycobacterial and cytotoxic activity. A rigorous Virtual Screening Workflow (VSW) of the tentatively identified phytocompounds was then employed to identify potential inhibitor/s of M. tuberculosis pantothenate kinase (PanK). Molecular dynamics simulations and post-MM-GBSA free energy calculations were used to determine the potential mode of action and selectivity of selected phytocompounds. The results showed that plant crude extracts generally exhibited poor antimycobacterial activity, except for R. caffra and S. molle which exhibited average efficacy against M. tuberculosis H37Rv with minimum inhibitory concentrations between 0.25–0.125 mg/mL. Only one compound with a favourable ADME profile, namely, norajmaline was returned from the VSW. Norajmaline exhibited a docking score of –7.47 kcal/mol, while, pre-MM-GBSA calculation revealed binding free energy to be –37.64 kcal/mol. All plant extracts exhibited a 50% inhibitory concentration (IC50) of

Abstract The death of many people in tropical countries can be attributed to microbial infection, probably, because synthetic antibiotics are failing in the treatment of most microbial infections, attributed to the ability of the microorganisms to mutate and adapt to harsh conditions. This study evaluated, in vitro, the antimicrobial activities, antioxidant potentials, and the total phenolic as well as phytochemical contents of aqueous and ethanol extracts of the root of Cryptolepis sanguinolenta (Lindl.) and the crude sap of Pycnanthus angolensis (Welw) using selected standard bacteria strains (Staphylococcus aureus (ATCC 25,923), Staphylococcus saprophyticus (ATCC 15,305), Escherichia coli (ATCC 25,922), Salmonella typhi (ATCC 19,430), Pseudomonas aeruginosa (ATCC 27,853), and Proteus mirabilis (ATCC 49,565). The modified agar well diffusion method was used to evaluate the antimicrobial activities of the plant extracts. Chloramphenicol and tetracycline were used as positive controls. The extracts were screened for specific phytochemicals with total phenolic contents were determined using Folin Ciocalteu reagent test. The phytoconstituents observed were alkaloids, cardiac glycosides, and saponins in both Cryptolepis sanguinolenta and Pycnanthus angolensis. For the antimicrobial activities, all the test bacteria were susceptible to the crude sap of Pycnanthus angolensis except Proteus mirabilis. In the case of the Cryptolepis sanguinolenta, only S. aureus was susceptible to both aqueous and ethanol extracts. The total phenolic content, expressed in g/100 g GAE, recorded values of 55.427 ± 4.248 for the crude sap of Pycnanthus angolensis, and 11.642 ± 4.248 and 26.888 ± 4.248 for the aqueous and ethanol extracts of Cryptolepis sanguinolenta, respectively. It is concluded that Cryptolepis sanguinolenta and Pycnanthus angolensis are excellent candidates for further development of antimicrobial agents in the fight against microbial infections given the pressing need for novel efficacious agents.