Smilax aspera L. (commonly known as sarsaparilla) is recognized for its composition rich in flavonoids, phenylpropanoids, steroidal saponins, stilbenoids, and tannins, exhibiting anti-inflammatory, cytotoxic, and antimicrobial properties. This study investigates the hydromethanolic extracts of its leaves and fruits through vibrational spectroscopy and gas chromatography–mass spectrometry, evaluating their potential as biorationals for safeguarding crops. Analysis of S. aspera leaf and fruit extracts revealed the presence of phytochemicals such as lactones and other furan derivatives. In vitro assessments against three phytopathogens—Erwinia amylovora, Pseudomonas syringae pv. actinidiae, and Xanthomonas campestris pv. campestris—demonstrated strong antibacterial activity, with minimum inhibitory concentration (MIC) values of 1500 μg·mL−1 for both extracts. Biofilm tests indicated that the leaf extract reduced biofilm formation by 78–85%, while the fruit extract led to a reduction of 73–92.5%. At a concentration of 750 µg·mL−1, the extracts caused a decrease in amylovoran synthesis by 41–58%. Additionally, noticeable alterations in membrane permeability were observed at MIC and MIC/2 doses. Subsequent in vivo trials conducted on Pyrus communis L. trees utilizing the combined aerial part extract yielded substantial protection against E. amylovora at a dose of 1500 μg·mL−1, reaching 80% wilting reduction for the leaf extract. The findings presented herein cast S. aspera extracts as a promising natural-based treatment against these bacterial phytopathogens.
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