背景:抗微生物药物耐药的幽门螺杆菌(H.幽门螺杆菌)构成了重大的公共卫生问题,特别是考虑到阿奇霉素耐药菌株的治疗选择有限。因此,新的研究有必要重新考虑阿奇霉素的使用,对许多菌株的有效性有所下降。因此,我们旨在通过将阿奇霉素与姜黄素以不同的配方组合来增强阿奇霉素的抗螺杆菌特性,包括丁香油中的姜黄素,姜黄素纳米金乳剂,和姜黄素纳米乳液。
方法:研究化合物的抗菌活性,无论是单独还是与其他抗螺杆菌药物联合使用,进行了评估。使用表型和基因型方法评估了它们的抗生物膜和抗毒力特性,除了分子对接研究。通过小鼠保护试验和组织病理学分析进一步验证了我们的发现。
结果:我们观察到姜黄素有很高的抗螺杆菌活性,尤其是姜黄素纳米乳液。在姜黄素纳米乳剂和阿奇霉素之间检测到协同作用,其中部分抑制浓度指数(FICI)值<0.5。姜黄素纳米乳剂是被检查物质中最具活性的抗生物膜和抗毒性化合物。在用姜黄素纳米乳液处理后,生物膜相关毒力基因(babA和hopQ)和ureA基因下调(倍数变化<1)。在蛋白质水平上,根据分子对接研究记录了姜黄素纳米乳的抗毒力活性.这些发现与攻击小鼠的组织病理学评分一致,肯定姜黄素纳米乳/阿奇霉素组合的优越疗效。
结论:所有姜黄素物理形式的抗螺杆菌活性都存在重大挑战,因为它们的最低抑制浓度(MIC)值较高,超过了最大允许水平。然而,在亚MIC水平使用姜黄素纳米乳可以增强阿奇霉素的抗螺杆菌活性,并表现出抗毒力特性,从而改善患者的预后并解决耐药病原体。因此,需要更广泛的研究来评估在幽门螺杆菌治疗中掺入姜黄素纳米乳的安全性.
BACKGROUND: Antimicrobial-resistant Helicobacter pylori (H. pylori) poses a significant public health concern, especially given the limited therapeutic options for azithromycin-resistant strains. Hence, there is a necessity for new studies to reconsider the use of azithromycin, which has diminished in effectiveness against numerous strains. Thus, we aimed to augment azithromycin\'s anti-Helicobacter properties by combining it with curcumin in different formulations, including curcumin in clove oil, curcumin nano-gold emulsion, and curcumin nanoemulsion.
METHODS: The antimicrobial activities of the investigated compounds, both individually and in combination with other anti-Helicobacter drugs, were evaluated. Their antibiofilm and anti-virulence properties were assessed using both phenotypic and genotypic methods, alongside molecular docking studies. Our findings were further validated through mouse protection assays and histopathological analysis.
RESULTS: We observed high anti-Helicobacter activities of curcumin, especially curcumin nanoemulsion. A synergistic effect was detected between curcumin nanoemulsion and azithromycin with fraction inhibitory concentration index (FICI) values <0.5. The curcumin nanoemulsion was the most active anti-biofilm and anti-virulence compound among the examined substances. The biofilm-correlated virulence genes (babA and hopQ) and ureA genes were downregulated (fold change <1) post-treatment with curcumin nanoemulsion. On the protein level, the anti-virulence activities of curcumin nanoemulsion were documented based on molecular docking studies. These findings aligned with histopathological scoring of challenge mice, affirming the superior efficacy of curcumin nanoemulsion/azithromycin combination.
CONCLUSIONS: The anti-Helicobacter activities of all curcumin physical forms pose significant challenges due to their higher minimum inhibitory concentration (MIC) values exceeding the maximum permissible level. However, using curcumin nanoemulsion at sub-MIC levels could enhance the anti-Helicobacter activity of azithromycin and exhibit anti-virulence properties, thereby improving patient outcomes and addressing resistant pathogens. Therefore, more extensive studies are necessary to assess the safety of incorporating curcumin nanoemulsion into H. pylori treatment.