article · Molecules
Chemical profiling of Pelargonium x hortorum root extracts revealed high concentrations of catechin and gallic acid, while lacking umckalin found in Pelargonium sidoides. When tested against 19 clinical isolates of Pseudomonas aeruginosa, the extracts showed antibacterial minimum inhibitory concentrations between 512 and 1024 micrograms per millilitre. Investigating the individual and combined effects of catechin and gallic acid demonstrated substantial anti-biofilm activity, decreasing the proportion of strong and moderate biofilm-forming isolates from 52.63 percent to 5.26 percent. Molecular investigations showed that the combination downregulated the quorum-sensing genes lasI and lasR in multiple isolates and achieved high computational docking scores against the LasR protein. Furthermore, the combination provided in vivo protective effects, increasing survival rates in infected mice.
Pseudomonas aeruginosa infections are difficult to treat because the bacteria form protective biofilms and use quorum-sensing communication to coordinate virulence. Identifying natural compound combinations that disrupt these mechanisms provides a way to reduce bacterial pathogenicity and improve host survival, presenting a promising alternative to conventional antimicrobial strategies.
This work could inform the development of anti-virulence or anti-biofilm therapeutics targeting Pseudomonas aeruginosa, of interest to pharmaceutical developers and biotechnology firms. Given that testing is limited to in vitro assays, molecular docking, and initial mouse models, the technology represents early-stage research that requires formulation optimisation, toxicity testing, and extensive preclinical and clinical validation before commercial application.
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HPLC-UV was used to compare the major constituents of two <i>Pelargonium × hortorum</i> cultivars and <i>Pelargonium sidoides</i> root extract. It revealed the presence of catechin and gallic acid in high concentrations and the absence of umckalin in <i>P. × hortorum</i> root extracts. The antibacterial activity of these extracts was screened against 19 <i>Pseudomonas aeruginosa</i> clinical isolates. <i>P. × hortorum</i> root extracts showed the lowest MIC values (512-1024 µg/mL). This activity was concluded to be attributable to the high concentrations of catechin and gallic acid. The anti-biofilm activity of catechin, gallic acid, and their combination was examined by a crystal violet assay. The combination reduced the percentage of strong and moderate biofilm-forming isolates from 52.63% to 5.26%. The impact on <i>las</i>I and <i>las</i>R genes expression using qRT-PCR and simultaneous docking against <i>Las</i>R protein was explored. The combination downregulated <i>las</i>I and <i>las</i>R gene expression in eight and six <i>P. aeruginosa</i> isolates, respectively, and showed the greatest docking score. Additionally, the in vivo protection capability of this combination in infected mice showed enhancement in the survival rate. Our study revealed the potential biofilm and quorum-sensing-inhibitory activity of the catechin and gallic acid combination as a novel alternative to inhibit bacterial pathogenicity.
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DOI: 10.3390/molecules27227841
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