Abreu-Pereira César Augusto, Gorayb-Pereira Ana Luiza, Jordão Cláudia Carolina, Bitencourt Gabriel Popazoglo, Cilli Eduardo Maffud, Pavarina Ana Cláudia
São Paulo State University (UNESP), School of Dentistry, Araraquara, Brazil.
São Paulo State University (UNESP), Institute of Chemistry, Araraquara, Brazil.
Lasers Med Sci. 2025 Jun 25;40(1):299. doi: 10.1007/s10103-025-04552-2.
Zerumbone (ZER), a sesquiterpene extracted from Zingiber zerumbet (L.) Smith, enhances the antibiofilm effects of antimicrobial photodynamic therapy (aPDT) by reducing the extracellular matrix of biofilms and increasing the generation of reactive oxygen species (ROS) when applied prior to aPDT. To reduce treatment application time, ZER was combined with Photodithazine® (PDZ) in a single solution. Then, this study investigated the potential of aPDT mediated by a mixture of ZER with PDZ in the inactivation of Staphylococcus aureus, Escherichia coli, fluconazole-susceptible (CaS) and resistant (CaR) Candida albicans biofilms. The solutions of ZER, PDZ and their mixture (ZER + PDZ) were analyzed using absorbance spectroscopy (AS), high-performance liquid chromatography (HPLC), and mass spectrometry (MS) to confirm the absence of molecular alterations in the mixture of ZER + PDZ. 48 h-biofilms were growth and treatments were performed: 1-ZER (256 µg/mL); 2-PDZ (200 µg/mL); 3-PDZ + LED; 4-ZER + PDZ + LED; 5- MIX (ZER + PDZ) + LED; Control (without treatment). Irradiation was performed using a red LED (660 nm, 50 J/cm², 30 mW/cm²). Sterile PBS was employed as the control group. For cytotoxicity assessments ffi broblast (HGF) and keratinocyte (NOK-si) oral cells were cultured for 24 h and submitted to treatments. Both ZER + PDZ + LED and MIX (ZER + PDZ) + LED groups showed the greatest statistically significant reduction in CFU/mL when compared to the control group (p ≤ 0.011) in all evaluated strain, with no significant difference between them (p ≥ 0.218). The reduction observed was 2.74, 2.89, 2.45 and 2.07 log for S. aureus, E. coli, CaS, CaR, respectively. Cell viability reduction in NOK-si and FGH did not exceed 17%. AS, HPLC, and MS analyses demonstrated that PDZ retained its original characteristics following combination with ZER. Zerumbone combined with PDZ enhances the effect of antimicrobial photodynamic treatment regardless of strain characteristics and showed no cytotoxic effects.
姜酮（ZER）是从红球姜（Zingiber zerumbet (L.) Smith）中提取的一种倍半萜，在抗菌光动力疗法（aPDT）之前应用时，可通过减少生物膜的细胞外基质并增加活性氧（ROS）的生成来增强aPDT的抗生物膜作用。为了减少治疗应用时间，将ZER与光二噻嗪（Photodithazine®，PDZ）混合在单一溶液中。然后，本研究调查了ZER与PDZ混合物介导的aPDT在金黄色葡萄球菌、大肠杆菌、氟康唑敏感（CaS）和耐药（CaR）白色念珠菌生物膜失活中的潜力。使用吸光光谱法（AS）、高效液相色谱法（HPLC）和质谱法（MS）分析ZER、PDZ及其混合物（ZER + PDZ）的溶液，以确认ZER + PDZ混合物中不存在分子变化。培养48小时的生物膜并进行处理：1-ZER（256μg/mL）；2-PDZ（200μg/mL）；3-PDZ + LED；4-ZER + PDZ + LED；5-MIX（ZER + PDZ）+ LED；对照（未处理）。使用红色LED（660nm，50J/cm²，30mW/cm²）进行照射。使用无菌磷酸盐缓冲盐水（PBS）作为对照组。为了进行细胞毒性评估，将成纤维细胞（HGF）和角质形成细胞（NOK-si）口腔细胞培养24小时并进行处理。与对照组相比，ZER + PDZ + LED组和MIX（ZER + PDZ）+ LED组在所有评估菌株中CFU/mL的降低均具有统计学意义（p≤0.011），且两组之间无显著差异（p≥0.218）。观察到的金黄色葡萄球菌、大肠杆菌、CaS、CaR的降低分别为2.74、2.89、2.45和2.07个对数。NOK-si和FGH中的细胞活力降低不超过17%。AS、HPLC和MS分析表明，PDZ与ZER结合后保留了其原始特性。姜酮与PDZ联合使用可增强抗菌光动力治疗的效果，且不受菌株特性影响，并且没有细胞毒性作用。
