Diarylheptanoids from Alnus viridis ssp. viridis and Alnus glutinosa: Modulation of Quorum Sensing Activity in Pseudomonas aeruginosa

Abstract

Diarylheptanoids from the barks of <i>Alnus viridis</i> ssp. <i>viridis</i> (green alder) and <i>Alnus glutinosa</i> (black alder) were explored for anti-quorum sensing activity. Chemicals with anti-quorum sensing activity have recently been examined for antimicrobial applications. The anti-quorum sensing activity of the selected diarylheptanoids was determined using two biosensors, namely <i>Pseudomonas aeruginosa</i> PAO1 and <i>Chromobacterium violaceum</i> CV026. Although all of the investigated compounds negatively influenced the motility of <i>P. aeruginosa</i> PAO1, four were able to inhibit biofilm formation of this human opportunistic pathogen for 40-70 %. Three of the diarylheptanoids (<b>3, 4</b>, and <b>5</b>) negatively influenced the biosynthesis of pyocyanin, which is under the control of quorum sensing. Platyphyllenone (<b>7</b>) and hirsutenone (<b>5</b>) were able to inhibit the biosynthesis of violacein in <i>C. violaceum</i> CV026, with <b>5</b> being able to inhibit the synthesis of both biopigments. Only one of the tested diarylheptanoids (<b>1</b>) was shown to significantly decrease the production of acyl homoserine lactones (AHL) in <i>P. aeruginosa</i> PAO1, more specifically, production of the long chain N-(3-oxododecanoyl)-l-HSL. On the other side, four diarylheptanoids (<b>2</b>-<b>5</b>) significantly reduced the synthesis of 2-alkyl-4-quinolones, part of the <i>P. aeruginosa</i> quinolone-mediated signaling system. To properly assess therapeutic potential of these compounds, their <i>in vitro</i> antiproliferative effect on normal human lung fibroblasts was determined, with doses affecting cell proliferation between 10 and 100 µg/mL. This study confirms that the barks of green and black alders are rich source of phytochemicals with a wide range of biological activities that could further be exploited as natural agents against bacterial contaminations and infections.