Phytochemical Characterization and Integrated Biological Evaluation of Baccharis dracunculifolia DC Ethanol Extract: Antioxidant, Anti-Inflammatory and Toxicological Evidence

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.