Synergistic Effect of Biosynthesized Silver Nanoparticles and Natural Phenolic Compounds against Drug-Resistant Fish Pathogens and Their Cytotoxicity: An In Vitro Study

Abstract

Fish pathogens causing disease outbreaks represent a major threat to aquaculture industry and food security. The aim of the presented study is to develop safe and effective bioactive agents against two bacterial isolates: Aeromonas hydrophila and Pseudomonas fluorescens. We employed a broth microdilution method to investigate the antibacterial effect of biosynthesized silver nanoparticles (AgNPs); rutin, a natural flavonoid extracted from Ruta graveneoles; and heliomycin, a secondary metabolite produced by marine actinomycetes AB5, as monotherapeutic agents. Moreover, AgNPs in combination with rutin (AgNP + R) and heliomycin (AgNPs + H) were examined for their synergistic effect. The cytotoxic effect of individual bioactive compounds and in combination with AgNPs was investigated on epithelioma papulosum cyprini (EPC) fish cell lines. Individual treatment of AgNPs, rutin, and heliomycin exhibited a dose-dependent antimicrobial activity against A. hydrophila and P. fluorescens. Rutin minimum inhibitory concentration (MIC) showed the lowest cytotoxicity when tested on EPC cell lines, while heliomycin MIC was highly cytotoxic. Combined subtherapeutic doses of AgNPs + R and AgNPs + H displayed additive and synergistic effects against A. hydrophila and P. fluorescens, respectively, with improved results and relative safety profile. The study findings demonstrate that a combination of AgNPs and natural bioactive compounds may represent novel therapeutics fighting fish pathogens potentially affecting the fish farming industry.

Rutin: A Flavonoid as an Effective Sensitizer for Anticancer Therapy; Insights into Multifaceted Mechanisms and Applicability for Combination Therapy

“…erefore, the present review aimed to show the synergistic effects of rutin with anticancer drugs in cancer cell lines (Table 2). Rutin was demonstrated to target various inflammatory, apoptotic, autophagic, and angiogenic signalling mediators, including nuclear factor-κB, tumor necrosis factor-α, interleukins, light chain 3/Beclin, B cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein, caspases, and vascular endothelial growth factor [40,81]. A critical analysis of the anticancer potential of rutin and associated molecular targets among various cancer types has not been performed previously.…”

“…A critical analysis of the anticancer potential of rutin and associated molecular targets among various cancer types has not been performed previously. Moreover, combination therapy can lead to a decrease in drug resistance and chemotherapeutic side effects [40,[78][79][80][81][82]. 6…”

Biosynthesis and Characterization of Calcium Oxide Nanoparticles from Citrullus colocynthis Fruit Extracts; Their Biocompatibility and Bioactivities

“…The findings of our study are in accordance with previously reported research by Eram et al [ 58 ]. Nanoparticles show better bioactivities and safety when used synergistically with plant extracts due to the fabrication of bioactive phytochemicals on their surface [ 59 , 60 , 61 ]. In this study, we have also found that synergistic solution of CaONPs and CCFE show less toxicity and enhanced bioactivity.…”

A new strategy to achieve high antimicrobial activity: green synthesised silver nanoparticle formulations with Galium aparine and Helichrysum arenarium

“…Despite these limitations of our study, our findings of the synergistic effects of the two synthesised nanoparticles when combined seem to support some earlier reports of improved antimicrobial effects by combinations of AgNPs with tomato, onion, acacia, neem, Eucalyptus globulus, Trichophyton rubrum , or garlic ( 57 – 61 ). One study that combined AgNPs synthesised with the rutin flavonoid and heliomycin antibiotic reported dose-dependent and synergistic antibacterial activity against Aeromonas hydrophila and Pseudomonas fluorescens ( 62 ).…”