Khumbulani Madonsela, Alayande Kazeem Adekunle, Sabiu Saheed
Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, Durban, South Africa.
Unit for Environmental Sciences and Management, North-West University, Potchefstroom, South Africa.
Evid Based Complement Alternat Med. 2022 May 9;2022:3809232. doi: 10.1155/2022/3809232. eCollection 2022.
Bacterial resistance to colistin has prompted the search for alternative strategies to enhance antibacterial potential. Combination therapy remains one of the viable strategies in antibacterial therapy and has been proven to be effective in reducing the risk of resistance. In this study, the potential of orientin for enhancing the antibacterial activity of colistin was assessed against and . The involvement of oxidative stress in such enhancement was also assessed. The minimum inhibitory concentrations (MICs) of colistin and orientin were 16 g/mL and 64 g/mL against and 64 g/mL and 256 g/mL against respectively. For the combination therapy, orientin potentiates the antibacterial effect of colistin with a friction inhibitory concentration index (FICI) of 0.37 and 0.31 against and , respectively. This observation suggests a synergistic interaction, with the MIC of colistin being reduced by 3- and 4-fold in the presence of orientin against and , respectively. Additionally, treatment with the combination of colistin and orientin induced oxidative stress against both organisms through increased cellular levels of superoxide anion radicals with concomitant increase in NAD/NADH and ADP/ATP ratios. These findings suggest that orientin enhanced colistin in the killing of the test bacteria and the cotreatment of colistin and orientin induced oxidative stress, through reactive oxygen species generation, which consequently facilitated bacterial lethality without causing drug-drug interactions. Although, the data presented in this study has supported the capability of orientin for strengthening antibacterial activity of colistin toward the fight against drug-resistant Gram-negative bacteria, studies focusing on the exact target and mechanism of action of orientin are underway.
细菌对黏菌素的耐药性促使人们寻找增强抗菌潜力的替代策略。联合治疗仍然是抗菌治疗中可行的策略之一，并且已被证明在降低耐药风险方面是有效的。在本研究中，评估了荭草素增强黏菌素抗菌活性的潜力，受试对象为[具体受试对象1]和[具体受试对象2]。还评估了氧化应激在此类增强作用中的参与情况。黏菌素和荭草素对[具体受试对象1]的最低抑菌浓度（MIC）分别为16 μg/mL和64 μg/mL，对[具体受试对象2]的最低抑菌浓度分别为64 μg/mL和256 μg/mL。对于联合治疗，荭草素增强了黏菌素的抗菌效果，对[具体受试对象1]和[具体受试对象2]的联合抑菌浓度指数（FICI）分别为0.37和0.31。这一观察结果表明存在协同相互作用，在荭草素存在的情况下，黏菌素对[具体受试对象1]和[具体受试对象2]的MIC分别降低了3倍和4倍。此外，黏菌素和荭草素联合处理通过增加超氧阴离子自由基的细胞水平以及伴随的NAD/NADH和ADP/ATP比值升高，对两种受试菌都诱导了氧化应激。这些发现表明，荭草素增强了黏菌素对受试细菌的杀灭作用，并且黏菌素和荭草素联合处理通过产生活性氧诱导了氧化应激，从而促进了细菌死亡，且未引起药物相互作用。尽管本研究提供的数据支持了荭草素增强黏菌素抗耐药革兰氏阴性菌活性的能力，但针对荭草素的确切靶点和作用机制的研究正在进行中。
