Antibacterial synergy between rutin and florfenicol enhances therapeutic spectrum against drug resistant Aeromonas hydrophila.

Emergence of antibiotic resistant bacteria has necessitated the drive to explore competent antimicrobial agents or to develop novel formulations to treat infections including Aeromonas hydrophila. The present study investigates the synergistic antibacterial effects of citrus flavonoid rutin and florfenicol (FF) against A. hydrophila in vitro and in vivo. Rutin is extracted and purified from Citrus sinensis peel through preparative HPLC and characterized through TLC, GC-MS and 1H and 13C NMR analyses. Though rutin did not display significant antibacterial activity, it modulated FF activity resulting in four-fold reduction in the MIC value for FF. The anti-biofilm potential of synergistic association of rutin and FF was validated by protein analysis, quantification of exopolysaccharide (EPS) and microscopy studies using sub-MIC doses. Besides antibacterial action, in vivo studies showed that Rutin/FF combination enhanced host immunity by improving blood cell count, anti-protease, and lysozyme activities as well as decreased the oxidative stress and the pathological changes of tilapia Oreochromis niloticus against A. hydrophila infection. No significant DNA damages or clastogenic effects were detected in tilapia challenged with A. hydrophila under Rutin/FF treatment. It is shown that an acute-phase Lipopolysaccharide binding protein (LBP) enhances the innate host defence against bacterial challenge. Semi quantitative RT-PCR and western blot results revealed the significant increase of LBP in the supernatant of tilapia monocytes/macrophages challenged with A. hydrophila upon treatment. The study findings substantiate that the combination of natural molecules with antibiotics may open up possibilities to treat MDR strains.

A novel rutin-fucoidan complex based phytotherapy for cervical cancer through achieving enhanced bioavailability and cancer cell apoptosis.

Recent studies on flavonoids forming complexes with macromolecules attract researchers due to their enhanced bioavailability as well as chemo-preventive efficacy. In this study, a flavonoid rutin (Ru) is non-covalently complexed with fucoidan (Fu) using the functional groups to obtain a therapeutic polymeric complex overcoming the limitations of bioavailability of rutin. The prepared novel rutin-fucoidan (Ru-Fu) complex is characterized for spectroscopic features, particle size and distribution analysis by DLS. It is shown that the complex displayed the nanostructural features that are different from that of the usual rutin-fucoidan mixture. The studies on drug release profiles at different pH (5.5, 6.8 and 7.4) show that the sustained release of compounds from complex occurs preferentially at the desired endosomal pH (5.5). Further, the chemopreventive potential of Ru-Fu complex is investigated against HeLa cells by cellular apoptotic assays and flow cytometric analysis. It showed that the complex is able to disrupt cell cycle regulation and has the ability to induce cellular apoptosis via nuclear fragmentation, ROS generation and mitochondrial potential loss. In vitro cell viability assay with Ru-Fu complex shows that the complex is biocompatible on normal cells. The hemolysis assay also reveals that the complex does not release hemoglobin from human red blood cells (RBCs). Thus, the study is envisaged to open up interests for developing such formulations against cervical cancer and other cancers.