Nasution Haris M, Yulyana Ana, Utama Rezza F, Bangar Roy I, Kaban Vera E, Daulay Wardiyah, Astyka Ririn, Lubis Muhammad F
Department of Pharmacy, Faculty of Pharmacy, Universitas Muslim Nusantara Al-Washliyah, Medan, Indonesia.
Department of Pharmacy, Faculty of Pharmacy, Institut Sains dan Teknologi Nasional, Jakarta, Indonesia.
Narra J. 2025 Apr;5(1):e1939. doi: 10.52225/narra.v5i1.1939. Epub 2025 Feb 14.
The rising incidence of multidrug-resistant (MDR) infections underscores the urgent need for novel antimicrobial strategies. The aim of this study was to investigate the synergistic effects between a polyphenol-rich extract from fruit and tetracycline against MDR strains. The extraction process was optimized using the Box-Behnken design approach to maximize the total phenolic content (TPC) of the extract. Key variables, including ethanol concentration, extraction time, and solid-to-liquid ratio (w/v), were determined through single-factor experiments. The antimicrobial activity of the extract, both alone and in combination with tetracycline, was evaluated against . Mechanistic studies focusing on bacterial lysis and efflux pump inhibition were conducted to assess the extract's effects and its combined potential with tetracycline. The Box-Behnken design successfully optimized the extraction conditions, yielding the highest TPC at 68.92% ethanol concentration, 1.85 days of extraction time, and a 1:9.58 w/v ratio. The predicted and experimentally verified TPC values of the extract were 129.19 and 130.76 ± 2.46 mg GAE/g samples, respectively, with no significant difference ( > 0.05). The extract contained several phenolic compounds identified using liquid chromatography-high-resolution mass spectrometry (LC-HRMS). It exhibited antimicrobial activity against MDR , either alone or in combination with tetracycline. The combination demonstrated a synergistic effect against MDR , with a fractional inhibitory concentration index (FICI) of 0.37. Moreover, the combination showed superior bacteriolytic effects against MDR cells, as evidenced by increased release of nucleic acid components and membrane destabilization, compared to the extract or tetracycline alone ( < 0.0001 for all comparisons). Additionally, the combination significantly enhanced the efflux pump inhibition effect compared to the extract or tetracycline alone ( < 0.05 for both). These findings support the potential use of polyphenol-rich extracts as adjuncts to conventional antibiotics in treating drug-resistant bacterial infections.
多重耐药（MDR）感染发病率的上升凸显了对新型抗菌策略的迫切需求。本研究的目的是调查富含多酚的水果提取物与四环素对MDR菌株的协同作用。采用Box-Behnken设计方法优化提取工艺，以最大化提取物的总酚含量（TPC）。通过单因素实验确定了关键变量，包括乙醇浓度、提取时间和固液比（w/v）。评估了提取物单独以及与四环素联合使用时对……的抗菌活性。进行了聚焦于细菌裂解和外排泵抑制的机制研究，以评估提取物的作用及其与四环素联合的潜力。Box-Behnken设计成功优化了提取条件，在乙醇浓度68.92%、提取时间1.85天和1:9.58 w/v的比例下获得了最高的TPC。提取物的预测TPC值和实验验证值分别为129.19和130.76±2.46 mg GAE/g样品，无显著差异（>0.05）。该提取物含有几种通过液相色谱-高分辨率质谱（LC-HRMS）鉴定的酚类化合物。它单独或与四环素联合使用时均对MDR……表现出抗菌活性。该组合对MDR……显示出协同作用，部分抑制浓度指数（FICI）为0.37。此外，与单独的提取物或四环素相比，该组合对MDR……细胞表现出更强的溶菌作用，核酸成分释放增加和膜不稳定证明了这一点（所有比较中P<0.0001）。此外，与单独的提取物或四环素相比，该组合显著增强了外排泵抑制作用（两者均P<0.05）。这些发现支持了富含多酚的……提取物作为传统抗生素辅助剂用于治疗耐药细菌感染的潜力。
