Interaction of Ziziphus mucronata subsp. mucronata Methanol Extract and First-Line Antibiotics is Synergistic In Vitro through Production of Reactive Oxygen Species.

Aderonke Ariyike Olajuyigbe,Roger Murugas Coopoosamy,Olufunmiso Olusola Olajuyigbe

doi:10.1155/2020/4087394

Aderonke Ariyike Olajuyigbe, Roger Murugas Coopoosamy + Show 1 more

Open Access

https://doi.org/10.1155/2020/4087394

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Abstract

With the increased incidence of antibacterial resistance in microorganisms, combining natural products from plants with antibiotics may be considered interesting alternatives for synergy to attain multitarget effects. In this study, the antioxidant activity of the methanol extract of Ziziphus mucronata and its interactions with antibiotics against bacteria of clinical importance were investigated. While its phytochemicals and antioxidant activities were determined by free radical scavenging assays, the antibacterial activities of the extract and its interactions with the antibiotics were determined by macrobroth dilution and the checkerboard methods. From the results, total phenolic content was 29.67 ± 1.90 mg GAE/100 g, total flavonoid content was 8.72 ± 0.08 mg QE/100 g, and total proanthocyanidin content was 1.94 ± 0.00 mg CE/100 g of dry plant material. The inhibition concentration 50% (IC50) of DPPH, BHT, and ascorbic acid was equal to 0.04 ± 0.02 mg/ml, respectively. Those of the ABTS, BHT, and ascorbic acid were equal to 0.02 ± 0.02, 0.04 ± 0.03, and 0.04 ± 0.02 mg/ml, respectively. The checkerboard assay showed that combining the extract with different antibiotics resulted in synergistic (38.75%), indifferent (30%), additive (28.75%), and antagonistic (2.5%) interactions. The interactions between the extract and antibiotics resulting in enhanced antibacterial activities could have resulted from the antioxidant activities of the extract mopping up the ROS generated by the antibiotics or the ability of both extract and antibiotics simultaneously producing reactive oxygen species with deleterious effects resulting in synergistic antibacterial effects.

Highlights

Forming the basis for practicing sophisticated ethnomedicine and providing excellent leads for new drug developments [1], the therapeutic significance of medicinal plants has become a popularized knowledge well disseminated by virtue of their use in the treatment of microbial infections [2]
While the medicinal properties of many plants have been reported [3] and pharmacological activities are due to the bioactive compounds present in them [4], the therapeutic failures of the drugs available today, the scarcity of novel antibiotics [5], emergence of resistant pathogens, adverse effects and limited spectrum of action of the currently available drugs [6], and high level of toxicity and carcinogenicity associated with synthetic antioxidants such as butylated hydroxytoluene (BHT) and tert-butyl hydroquinone (TBHQ) [7] have propelled the need to focus attention on discovering new and better antimicrobial and antioxidant agents of plant origin
To further establish the therapeutic potential of this plant species, this study investigated the phytochemicals, antioxidant potentials, and the influence of the methanol extract of Ziziphus mucronata subsp. mucronata on the antibacterial activities of some antibiotics against different bacterial species in vitro to indicate the possible effects of reactive oxygen species (ROS) produced as a result of combining the extract with the antibiotics

Summary

Introduction

Forming the basis for practicing sophisticated ethnomedicine and providing excellent leads for new drug developments [1], the therapeutic significance of medicinal plants has become a popularized knowledge well disseminated by virtue of their use in the treatment of microbial infections [2]. While the medicinal properties of many plants have been reported [3] and pharmacological activities are due to the bioactive compounds present in them [4], the therapeutic failures of the drugs available today, the scarcity of novel antibiotics [5], emergence of resistant pathogens, adverse effects and limited spectrum of action of the currently available drugs [6], and high level of toxicity and carcinogenicity associated with synthetic antioxidants such as butylated hydroxytoluene (BHT) and tert-butyl hydroquinone (TBHQ) [7] have propelled the need to focus attention on discovering new and better antimicrobial and antioxidant agents of plant origin. While many phenolics have been known for their antioxidant and antimicrobial activities, many plants have remarkably combined with antibiotics to show varied degrees of interactions [14, 15] for which mechanisms of action are yet to be determined

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