Background/Objectives: Pereskia grandifolia Haw. is a plant native to Central and South America and belongs to the Cactaceae family, and it is valued in the human diet for its nutritional value. Recently, this species was reported to contain a variety of saponins, but structural details remain limited because of their number and complexity. Saponins exhibit pharmacological properties, making their characterization useful. Methods: Comprehensive mass spectrometry analysis, combined with chemical methylation of the entire saponins, provided critical information on the distribution of sugar moieties associated with the monosaccharides and the aglycone. We also assessed cellular antioxidant capacity, cytotoxicity, and antiproliferative effects against breast tumor cell lines by staining for Ki-67, Annexin V, and 7AAD. Results: Fifteen saponins were identified with oleanolic and ursolic acids. Oligosaccharides were formed by glucuronic acid, with additional glucose units attached to the glucuronic acid or the aglycone, which had not been reported previously. This fraction showed cytotoxic and antiproliferative effects against various tumor cell lines, with the best IC50 at 90 µg·mL⁻¹, and reduced chemotherapy-induced reactive oxygen species (ROS) levels. Whereas cytotoxic effects in most cell lines involved necrosis, MCF-7 exhibited antiproliferative and cytostatic effects, with apoptosis as the main death pathway. Conclusions: The methods used here enabled a comprehensive evaluation of saponins, eliminating the need for extensive purification. Even in a mixture, methylation provided critical structural details that enabled the characterization of different structures, including several isomers. The anti-ROS activity observed in this extract may be associated with modulating cytotoxic responses by preventing oxidative cell damage.

Background/Objectives: Baccharis dracunculifolia DC. is a medicinal plant and the primary botanical source of Brazilian green propolis. This study aimed to characterize the phytochemical profile of its ethanol extract and evaluate its antioxidant, anti-inflammatory, cytotoxic, and acute oral toxicity profiles. Methods: The extract was characterized by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS). Antioxidant and anti-inflammatory activities were evaluated by complementary in vitro assays, cytotoxicity in NIH/3T3 fibroblasts, and acute oral toxicity according to OECD Guideline 423 in Wistar rats at 300 and 2000 mg/kg. Results: UHPLC-QTOF-MS analysis resulted in the tentative annotation of 54 metabolites, including phenolic acids, flavonoids, caffeoylquinic acid derivatives, diterpenes, glycolipids, and saponins. The extract showed antioxidant activity, with a DPPH IC₅₀ of 0.77 ± 0.009 mg/mL and FRAP reducing capacity of 1.24 ± 0.22 µM ferrous sulfate/mg. Anti-inflammatory activity increased with concentration, reaching 58.60 ± 0.23%, 60.84 ± 0.40%, and 57.89 ± 2.96% inhibition of hemolysis, macrophage spreading, and phagocytosis, respectively, at 600 µg/mL (p < 0.05 vs. negative control). NIH/3T3 viability remained above 70% at all tested concentrations and exposure times. No mortality, treatment-related clinical signs, or significant changes in body weight, hematological and biochemical parameters, relative organ weights, or histopathological findings were observed at doses up to 2000 mg/kg. Conclusions: The B. dracunculifolia ethanol extract exhibited antioxidant and anti-inflammatory activities in vitro, without relevant cytotoxicity under the tested conditions, and showed no evidence of acute oral toxicity at doses up to 2000 mg/kg.