Serratia marcescens is one of the important nosocomial pathogens which rely on quorum sensing (QS) to regulate the production of biofilm and several virulence factors. Hence, blocking of QS has become a promising approach to quench the virulence of S. marcescens. For the first time, QS inhibitory (QSI) and antibiofilm potential of Actinidia deliciosa have been explored against S. marcescens clinical isolate (CI). A. deliciosa pulp extract significantly inhibited the virulence and biofilm production without any deleterious effect on the growth. Vanillic acid was identified as an active lead responsible for the QSI activity. Addition of vanillic acid to the growth medium significantly affected the QS regulated production of biofilm and virulence factors in a concentration dependent mode in S. marcescens CI, ATCC 14756 and MG1. Furthermore vanillic acid increased the survival of Caenorhabditis elegans upon S. marcescens infection. Proteomic analysis and mass spectrometric identification of differentially expressed proteins revealed the ability of vanillic acid to modulate the expression of proteins involved in S-layers, histidine, flagellin and fatty acid production. QSI potential of the vanillic acid observed in the current study paves the way for exploring it as a potential therapeutic candidate to treat S. marcescens infections.

Alzheimer's disease (AD) is a devastating brain disorder characterized by an increased level of amyloid-beta (Aβ) peptide deposition and neuronal cell death leading to an impairment of learning and thinking skills. The Aβ deposition is a key factor in senile plaques of the AD brain which cause the elevation of intracellular calcium ions and the production of formidable free radicals, both of which greatly contribute to the AD-associated cascade, leading to unstoppable neuronal loss in the hippocampal region of the brain. Natural products are currently considered as an alternative strategy for the discovery of novel multipotent drugs against AD. They include the naturally occurring dietary soy isoflavone genistein which has been recognized to possess several health-promoting effects. Genistein has been mainly focused because of its potential on amelioration of Aβ-induced impairment and its antioxidant capacity to scavenge the free radicals produced in AD. It can also directly interact with the targeted signaling proteins and stabilize their activity to prevent AD. An improved understanding of the direct interactions between genistein and target proteins would contribute to the further development of AD treatment. This review mainly focuses on molecular targets and the therapeutic effects regulated by genistein, which has the ability to directly target the Aβ peptide and to control its activity involved in intracellular signaling pathways, which otherwise would lead to neuronal death in the hippocampal region of the AD brain.

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Inhibition of β-amyloid (Aβ) aggregation in the cerebral cortex of the brain is a promising therapeutic and defensive strategy in identification of disease modifying agents for Alzheimer’s disease (AD). Since natural products are considered as the current alternative trend for the discovery of AD drugs, the present study aims at the evaluation of anti-amyloidogenic potential of the marine seaweed Padina gymnospora. Prevention of aggregation and disaggregation of the mature fibril formation of Aβ 25–35 by acetone extracts of P. gymnospora (ACTPG) was evaluated in two phases by Thioflavin T assay. The results were further confirmed by confocal laser scanning microscopy (CLSM) analysis and Fourier transform infrared (FTIR) spectroscopic analysis. The results of antiaggregation and disaggregation assay showed that the increase in fluorescence intensity of aggregated Aβ and the co-treatment of ACTPG (250 μg/ml) with Aβ 25–35, an extensive decrease in the fluorescence intensity was observed in both phases, which suggests that ACTPG prevents the oligomers formation and disaggregation of mature fibrils. In addition, ACTPG was subjected to column chromatography and the bioactivity was screened based on the cholinesterase inhibitory activity. Finally, the active fraction was subjected to LC-MS/MS analysis for the identification of bioactive compounds. Overall, the results suggest that the bioactive compound alpha bisabolol present in the alga might be responsible for the observed cholinesterase inhibition with the IC50 value < 10 μg/ml for both AChE and BuChE when compared to standard drug donepezil (IC50 value < 6 μg/ml) and support its use for the treatment of neurological disorders.

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Biofilm formation, quorum sensing (QS)-regulated virulence and emergence of antibiotic resistance in bacterial pathogens lead to major health problems. In this perspective, antibiofilm agents and QS inhibitors have gained much attention to treat infections caused by antibiotic-resistant pathogens. For the first time, this investigation reports the antibiofilm and QS inhibitory potential of the brown macroalga Padina gymnospora against the nosocomial pathogen Serratia marcescens. The methanolic extract of P. gymnospora inhibited biofilm formation and the production of prodigiosin and protease. Successive solvent extraction, bioassay-guided fractionation of chloroform extract and GC-MS analysis of active fractions showed the presence of alphabisabolol with a relative abundance of 69 %. In vitro assays with alpha-bisabolol evidenced the potent inhibition of biofilm and QS-controlled prodigiosin, protease and swarming in S. marcescens, without exerting deleterious effect on its growth and metabolic activity. The results of this study exemplify the use of P. gymnospora and alpha-bisabolol as promising alternatives to antibiotics.

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