Abstract

Antibiotic resistance has emerged as a major global health challenge, underscoring the urgent need for alternative therapeutic strategies capable of enhancing the efficacy of existing antibiotics. In this context, saponin-based nanomaterials have attracted considerable attention due to their potential as antibiotic-modulating systems. This study investigated a saponin-enriched fraction obtained from the bark of Sarcomphalus joazeiro Mart. (SEF-4), its application in the green synthesis of silver nanoparticles, and the antibiotic-modulating potential of the resulting nanoformulation. SEF-4 was obtained from the ethanolic bark extract through liquid–liquid partitioning (52% yield), followed by column chromatographic purification and chemical characterization using LC-ESI-QTOF-MS. The purified fraction was subsequently employed as both a reducing and stabilizing agent for the synthesis of silver nanoparticles (putative AgNP-SEF-4), which were physicochemically characterized. Antibacterial activity and antibiotic-modulating effects were evaluated using the broth microdilution method against standard and multidrug-resistant bacterial strains. LC-ESI-QTOF-MS analysis enabled the putative identification of five jujubogenin-type triterpenoid saponins bearing tetra-, penta-, and hexasaccharide moieties with distinct glycosylation profiles; however, the precise sugar sequence, monosaccharide composition, and glycosidic linkage positions remain to be confirmed through complementary NMR and hydrolysis studies. Although neither SEF-4 nor putative AgNP-SEF-4 displayed clinically relevant intrinsic antibacterial activity, the nanoformulation significantly enhanced the activity of aminoglycoside antibiotics. The most pronounced modulatory effects were observed against Klebsiella pneumoniae ATCC 1705 in combination with amikacin and against both standard and multidrug-resistant Escherichia coli strains when combined with gentamicin or amikacin. These findings highlight the potential of putative AgNP-SEF-4 as an antibiotic adjuvant capable of potentiating aminoglycoside efficacy and increasing bacterial susceptibility, including in multidrug-resistant strains.

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