Zizyphus lotus L. is a perennial shrub particularly used in Algerian folk medicine, but little is known concerning the lipophilic compounds in the most frequently used parts, namely, root bark, pulp, leaves and seeds, which are associated with health benefits. In this vein, the lipophilic fractions of these morphological parts of Z. lotus from Morocco were studied by gas chromatography–mass spectrometry (GC–MS), and their antiproliferative and antimicrobial activities were evaluated. GC–MS analysis allowed the identification and quantification of 99 lipophilic compounds, including fatty acids, long-chain aliphatic alcohols, pentacyclic triterpenic compounds, sterols, monoglycerides, aromatic compounds and other minor components. Lipophilic extracts of pulp, leaves and seeds were revealed to be mainly composed of fatty acids, representing 54.3–88.6% of the total compounds detected. The leaves and seeds were particularly rich in unsaturated fatty acids, namely, (9Z,12Z)-octadeca-9,12-dienoic acid (2431 mg kg⁻¹ of dry weight) and (9Z)-octadec-9-enoic acid (6255 mg kg⁻¹ of dry weight). In contrast, root bark contained a high content of pentacyclic triterpenic compounds, particularly betulinic acid, accounting for 9838 mg kg⁻¹ of dry weight. Root bark extract showed promising antiproliferative activity against a triple-negative breast cancer cell line, MDA-MB-231, with a half-maximal inhibitory concentration (IC₅₀) = 4.23 ± 0.18 µg mL⁻¹ of extract. Leaf extract displayed interesting antimicrobial activity against Escherichia coli, methicillin-sensitive Staphylococcus aureus and Staphylococcus epidermis, presenting minimum inhibitory concentration (MIC) values from 1024 to 2048 µg mL⁻¹ of extract. Our results demonstrate that Zizyphus lotus L. is a source of promising bioactive components, which can be exploited as natural ingredients in pharmaceutical formulations.

Plant-derived pentacyclic triterpenic acids (TAs) have gained increasing attention due to their multiple biological activities. Betulinic acid (BA) and ursolic acid (UA) modulate diverse pathways in carcinogenesis, offering increased changes of success in refractory cancers, such as triple negative breast cancer (TNBC). The present work aimed to assess the metabolic effects of BA and UA in MDA-MB-231 breast cancer cells (TNBC model), as well as in MCF-10A non-cancer breast epithelial cells, with a view to unveiling the involvement of metabolic reprogramming in cellular responses to these TAs. Cell viability and cell cycle analyses were followed by assessment of changes in the cells exo- and endometabolome through ¹H NMR analysis of cell culture medium supernatants, aqueous and organic cell extracts. In MDA-MB-231 cells, BA was suggested to induce a transient upregulation of glucose consumption and glycolytic conversion, tricarboxylic acid (TCA) cycle intensification, and hydrolysis of neutral lipids, while UA effects were much less pronounced. In MCF-10A cells, boosting of glucose metabolism by the two TAs was accompanied by diversion of glycolytic intermediates to the hexosamine biosynthetic pathway (HBP) and the synthesis of neutral lipids, possibly stored in detoxifying lipid droplets. Additionally, breast epithelial cells intensified pyruvate consumption and TCA cycle activity, possibly to compensate for oxidative impairment of pyruvate glycolytic production. This study provided novel insights into the metabolic effects of BA and UA in cancer and non-cancer breast cells, thus improving current understanding of the action of these compounds at the molecular level.