Validation of the anti-infective potential of a polyherbal 'Panchvalkal' preparation, and elucidation of the molecular basis underlining its efficacy against Pseudomonas aeruginosa.

BACKGROUND

A Panchvalkal formulation (Pentaphyte P-5®) mentioned in ancient texts of Indian traditional medicine was investigated for its anti-infective potential against Pseudomonas aeruginosa.

METHODS

Effect of the test formulation on bacterial growth and pigment production was evaluated by broth dilution assay. In vivo efficacy was evaluated using Caenorhabditis elegans as the model host. Whole transcriptome approach was taken to study the effect of test formulation on bacterial gene expression.

RESULTS

This formulation in vitro was found to be capable of affecting quorum sensing (QS)-regulated traits (pyocyanin, pyoverdine, biofilm) of Pseudomonas aeruginosa. In combination with antibiotics, it enhanced susceptibility of the test bacterium to antibiotics like cephalexin and tetracycline. Effect of Panchvalkal formulation (PF) on QS-regulated traits of P. aeruginosa was not reversed even after repeated exposure of the bacterium to PF. In vivo efficacy of PF was demonstrated employing Caenorhabditis elegans as the model host, wherein PF-treated bacteria were able to kill lesser worms than their extract-unexposed counterparts. Whole transcriptome study revealed that approximately 14% of the P. aeruginosa genome was expressed differently under the influence of PF.

CONCLUSIONS

Major mechanisms through which Panchvalkal seems to exert its anti-virulence effect are generation of nitrosative and oxidative stress, and disturbing iron and molybdenum homeostasis, besides interfering with QS machinery. This study is a good demonstration of the therapeutic utility of the 'polyherbalism' concept, so common in ayurved. It also demonstrates utility of the modern 'omics' tools for validating the traditional medicine i.e. ayuromics.