Background/Objective: Cardiometabolic syndrome (CMS) is a complex clinical condition that encompasses metabolic dysregulation, cardiovascular disease, and diabetes risk factors. Worldwide, CMS is underdiagnosed, and its occurrence significantly increases cardiovascular morbimortality. Despite available pharmacological treatments, the approach is fragmented, and the associated clinical conditions are treated independently. This approach may be partially due to limited preclinical models to mimic the clinical conditions of CMS. Therefore, our study aims to present an innovative animal model of cardiometabolic syndrome and evaluate the effects of Baccharis dracunculifolia on the set of clinical alterations associated with the condition. Methods: Female Wistar rats were induced to develop diabetes, fed a cholesterol-enriched diet, and exposed to the smoke of 9 cigarettes/day for 6 weeks. During the last 2 weeks, the rats were treated with vehicle, B. dracunculifolia (30, 100, and 300 mg/kg), or a combination of simvastatin and insulin. At the end of the treatment, plasma lipid levels were measured, and the liver was analyzed histologically for hepatic lipid quantification and oxidative stress assessment. Results: Phytochemical analysis revealed seven phenolic acids and six flavonoids in the extract. B. dracunculifolia showed significant hepatoprotective effects, reducing AST and ALT levels and lowering both plasma and hepatic lipid levels. The extract also reversed hepatic steatosis and demonstrated antioxidant properties. Conclusions: These findings suggest that B. dracunculifolia may be a therapeutic option for the metabolic dysregulation present in CMS.

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.