Phytochemical Profile and Biological Activities of Baccharis dracunculifolia DC—Aerial-Parts Extract: In Vitro Evaluation and Predictive Analyses
Background and Objectives: Baccharis dracunculifolia DC. (Asteraceae), the main botanical source of Brazilian green propolis, is recognized for its high content of bioactive secondary metabolites. Given this potential, this study aimed to characterize the chemical profile of the crude extract (CE) from the aerial parts of B. dracunculifolia and to investigate its anti-inflammatory, antiproliferative, antioxidant, and photoprotective properties. Predictive computational analyses were used to assist the interpretation of the experimental findings. Methods: The CE was obtained by dynamic maceration with ethanol and chemically characterized by UHPLC-MS/MS using external calibration curves. Anti-inflammatory activity was evaluated by inhibiting nitric oxide (NO) in RAW 264.7 macrophages, while cellular antioxidant activity (CAA) was determined in the same model. Antiproliferative activity was evaluated against the human tumor cell lines AGS, Caco-2, MCF-7, and NCI-H460, as well as non-tumor VERO cells. Additionally, antioxidant potential was investigated using classical colorimetric methods (DPPH, FRAP, and ABTS). The extract was also quantified for total phenolic and flavonoid content, as well as sun protection factor (SPF). Furthermore, complementary computational analyses included PASS prediction, SwissTargetPrediction, Gene Ontology enrichment using PANTHER, SwissADME profiling, and toxicity prediction with ProTox-III. Results: UHPLC-MS/MS analysis revealed a profile rich in flavonoids and phenolic acids and led to the identification of 14 compounds not previously reported in B. dracunculifolia according to the literature examined, notably the flavonoid morin and the phenylpropanoid coniferaldehyde detected at comparatively high concentrations (>600 µg/g). CE inhibited NO production (IC50 = 62.00 µg/mL) suggesting anti-inflammatory activity, and reduced intracellular oxidation by 81% (at 2000 µg/mL) in RAW 264.7 macrophages. The extract showed total phenolic content (83.62 to 540.40 µg gallic acid equivalents/mg of CE) and high levels of flavonoids (472.00–515.00 µg quercetin equivalents/mg of CE), antioxidant activity in the DPPH assay (IC50 = 0.86 mg/mL), and relevant photoprotective potential (SPF = 7.79–19.30). Antiproliferative activity was moderate to weak (GI50 = 165.00–257.00 µg/mL). In silico analyses identified predicted activities, molecular targets, and enriched biological processes related to redox homeostasis, inflammation, apoptosis, and cellular responses to UV radiation, suggesting biological functions potentially associated with the identified metabolites. Conclusions: The crude extract of B. dracunculifolia demonstrated significant cellular anti-inflammatory and antioxidant activities, likely associated with its phenolic composition and the presence of metabolites reported in this study for the first time in this species, particularly morin and coniferaldehyde. These findings expand the phytochemical knowledge of B. dracunculifolia and reinforce its potential as a source of bioactive compounds for pharmaceutical, nutraceutical, and photoprotective applications.