Attenuation of Pseudomonas aeruginosa biofilm formation by Vitexin: A combinatorial study with azithromycin and gentamicin.

Microbial biofilm are communities of surface-adhered cells enclosed in a matrix of extracellular polymeric substances. Extensive use of antibiotics to treat biofilm associated infections has led to the emergence of multiple drug resistant strains. Pseudomonas aeruginosa is recognised as a model biofilm forming pathogenic bacterium. Vitexin, a polyphenolic group of phytochemical with antimicrobial property, has been studied for its antibiofilm potential against Pseudomonas aeruginosa in combination with azithromycin and gentamicin. Vitexin shows minimum inhibitory concentration (MIC) at 260 µg/ml. It's antibiofilm activity was evaluated by safranin staining, protein extraction, microscopy methods, quantification of EPS and in vivo models using several sub-MIC doses. Various quorum sensing (QS) mediated phenomenon such as swarming motility, azocasein degrading protease activity, pyoverdin and pyocyanin production, LasA and LasB activity of the bacteria were also evaluated. Results showed marked attenuation in biofilm formation and QS mediated phenotype of Pseudomonas aeruginosa in presence of 110 µg/ml vitexin in combination with azithromycin and gentamicin separately. Molecular docking of vitexin with QS associated LuxR, LasA, LasI and motility related proteins showed high and reasonable binding affinity respectively. The study explores the antibiofilm potential of vitexin against P. aeruginosa which can be used as a new antibiofilm agent against microbial biofilm associated pathogenesis.

New flavonol methyl ether from the leaves of Vitex peduncularis exhibits potential inhibitory activity against Leishmania donovani through activation of iNOS expression.

One new flavonol methyl ether (1), along with four known compounds from the leaves of methanol extract of Vitex peduncularis Wall and three known compounds from the leaves of methanol extract of Vitex pinnata Linn (Verbenaceae) were isolated. The chemical structure of the new compound was established by detailed spectroscopic studies. The in vitro antileishmanial activities of 1 against both Leishmania donovani promastigote and amastigote forms were evaluated. To characterize the effector mechanism of compound 1 against Leishmania parasite infected THP-1 macrophage cells, RT-PCR analysis of inducible nitric oxide synthase 2 (iNOS2) was done followed by measurement of nitric oxide generation by Griess reaction. Pentostam (sodium antimonygluconate) was used as reference drug. Compound 1 exhibited better antileishmanial activity than sodium antimonygluconate (SAG) (having IC50 values for promastigote, 2.4 and 58.5 µM and for amastigotes, 0.93 and 36.2 µM, respectively). Compound 1 was less toxic than SAG towards THP-1 having CC50 of 123.7 µM and 364.3 µM, respectively. Moreover, compound 1 was found to induce a potent host-protective response by enhancing NO generation and iNOS2 expression in infected macrophages to prevent the progression of Leishmania parasite.