Intestinal bacteria and filamentous fungi convert baccharin from Brazilian green propolis into non-cytotoxic metabolites

Brazilian green propolis has recognised commercial and medicinal value, with baccharin identified as one of its major bioactive compounds, exhibiting cytotoxicity against breast and prostate cancer cell lines. However, the activity of its metabolites remains poorly understood. This study investigated the biotransformation of baccharin by intestinal bacteria and filamentous fungi that mimic human metabolism. Cultures were incubated with 600 µL of baccharin (0.1 mg/mL in ethanol), yielding three metabolites. <i>Escherichia coli</i>, <i>Lactobacillus acidophilus</i>, <i>L. johnsonii</i>, and <i>Saccharomyces boulardii</i> hydrolysed baccharin to drupanin, with up to 79.1% conversion by <i>E. coli</i> after 48 h. <i>Cunninghamella elegans</i> and <i>Aspergillus alliaceus</i> catalysed hydrolysis, hydroxylation, and β-oxidation. Baccharin and its metabolites, evaluated at concentrations ranging from 1.56 to 200 µM, showed low or no cytotoxicity in normal (fibroblasts, MCF-10A, PNT-2) and tumour (MCF-7, MDA-MB-231, DU-145, PC-3) cell lines. Cisplatin and doxorubicin showed IC₅₀ values of 4.6–85.9 µM and &lt;0.78–5.99 µM, respectively, across cell lines.