Bendary Mahmoud M, Elmanakhly Arwa R, Mosallam Farag M, Alblwi Noaf Abdullah N, Mosbah Rasha A, Alshareef Walaa A, Selim Heba M R M, Alhomrani Majid, Alamri Abdulhakeem S, Safwat Nesreen A, Hamdan Ahmed M E, Elshimy Rana
Department of Microbiology and Immunology, Faculty of Pharmacy, Port Said University, Port Said, Egypt.
Department of Microbiology and Immunology, Faculty of Pharmacy, Modern University of Technology and Information, Cairo, Egypt.
Helicobacter. 2024 Jul-Aug;29(4):e13110. doi: 10.1111/hel.13110.
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.
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.
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.
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.
耐抗菌药物的幽门螺杆菌（H. pylori）引起了重大的公共卫生问题，特别是考虑到对阿奇霉素耐药菌株的治疗选择有限。因此，有必要开展新的研究，重新审视阿奇霉素的使用情况，因为它对许多菌株的有效性已经降低。因此，我们旨在通过将阿奇霉素与姜黄素以不同配方组合，包括丁香酚中的姜黄素、姜黄素纳米金乳液和姜黄素纳米乳剂，来增强阿奇霉素的抗幽门螺杆菌特性。
评估了所研究化合物单独以及与其他抗幽门螺杆菌药物联合使用时的抗菌活性。使用表型和基因型方法以及分子对接研究评估了它们的抗生物膜和抗毒力特性。我们的研究结果通过小鼠保护试验和组织病理学分析得到进一步验证。
我们观察到姜黄素，尤其是姜黄素纳米乳剂具有较高的抗幽门螺杆菌活性。在姜黄素纳米乳剂和阿奇霉素之间检测到协同效应，其分数抑制浓度指数（FICI）值<0.5。姜黄素纳米乳剂是所检测物质中最具活性的抗生物膜和抗毒力化合物。用姜黄素纳米乳剂处理后，与生物膜相关的毒力基因（babA和hopQ）和ureA基因下调（倍数变化<1）。在蛋白质水平上，基于分子对接研究记录了姜黄素纳米乳剂的抗毒力活性。这些发现与攻击小鼠的组织病理学评分一致，证实了姜黄素纳米乳剂/阿奇霉素组合的卓越疗效。
所有姜黄素物理形式的抗幽门螺杆菌活性都面临重大挑战，因为它们较高的最低抑菌浓度（MIC）值超过了最大允许水平。然而，在亚MIC水平使用姜黄素纳米乳剂可以增强阿奇霉素的抗幽门螺杆菌活性并表现出抗毒力特性，从而改善患者预后并应对耐药病原体。因此，有必要进行更广泛的研究来评估将姜黄素纳米乳剂纳入幽门螺杆菌治疗的安全性。
