Research Article 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, 1 Olufunmiso Olusola Olajuyigbe , 2,3 and Roger Murugas Coopoosamy 3 1 Department of Biochemistry, Olabisi Onabanjo University, Ago-Iwoye, Ogun State, Nigeria 2 Department of Microbiology, School of Science and Technology, Babcock University, PMB 4005, Ilisan-Remo, Ogun State, Nigeria 3 Department of Nature Conservation, Faculty of Natural Science, Mangosuthu University of Technology, Durban 4026, South Africa Correspondence should be addressed to Olufunmiso Olusola Olajuyigbe; funmijuyigbe12@yahoo.com Received 27 December 2019; Revised 19 February 2020; Accepted 9 March 2020; Published 8 April 2020 Academic Editor: Shyam Sundar Copyright © 2020 Aderonke Ariyike Olajuyigbe et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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 anti- bacterial 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. e inhibition concentration 50% (IC 50 ) of DPPH, BHT, and ascorbic acid was equal to 0.04 ± 0.02 mg/ml, respectively. ose 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. e 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. e 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. 1. Introduction Forming the basis for practicing sophisticated ethno- medicine and providing excellent leads for new drug developments [1], the therapeutic significance of medic- inal 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. Hindawi Journal of Tropical Medicine Volume 2020, Article ID 4087394, 9 pages https://doi.org/10.1155/2020/4087394