Boosting the Anti-Helicobacter Efficacy of Azithromycin through Natural Compounds: Insights From In Vitro, In Vivo, Histopathological, and Molecular Docking Investigations

IF 4.3 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Helicobacter Pub Date : 2024-07-12 DOI:10.1111/hel.13110

Mahmoud M. Bendary, Arwa R. Elmanakhly, Farag M. Mosallam, Noaf Abdullah N. Alblwi, Rasha A. Mosbah, Walaa A. Alshareef, Heba M. R. M. Selim, Majid Alhomrani, Abdulhakeem S. Alamri, Nesreen A. Safwat, Ahmed M. E. Hamdan, Rana Elshimy

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Abstract

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.

Conclusion

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.

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通过天然化合物提高阿奇霉素的抗辣根菌药效：体外、体内、组织病理学和分子对接研究的启示。

背景：幽门螺杆菌（H. pylori）对抗菌药产生耐药性是一个重大的公共卫生问题，特别是考虑到耐阿奇霉素菌株的治疗方案有限。因此，有必要开展新的研究，重新考虑阿奇霉素的使用，因为阿奇霉素对许多菌株的疗效已经减弱。因此，我们将阿奇霉素与姜黄素以不同的配方（包括姜黄素丁香油、姜黄素纳米金乳剂和姜黄素纳米乳剂）结合起来，旨在增强阿奇霉素的抗辣根菌特性：方法：对所研究化合物的抗菌活性进行了评估，包括单独使用以及与其他抗肝杆菌药物联合使用。使用表型和基因型方法以及分子对接研究评估了这些化合物的抗生物膜和抗病毒特性。小鼠保护试验和组织病理学分析进一步验证了我们的研究结果：结果：我们观察到姜黄素，尤其是姜黄素纳米乳液具有很高的抗肝杆菌活性。结果：我们观察到姜黄素特别是姜黄素纳米乳液具有很高的抗赫尔茨菌活性，姜黄素纳米乳液与阿奇霉素之间存在协同作用，其抑制浓度指数（FICI）值为结论：姜黄素纳米乳液与阿奇霉素之间存在协同作用：由于姜黄素的最低抑菌浓度 (MIC) 值较高，超过了最高允许水平，因此所有姜黄素物理形态的抗辣根菌活性都面临着巨大挑战。然而，使用 MIC 值以下的姜黄素纳米乳液可以增强阿奇霉素的抗赫尔希氏菌活性，并显示出抗病毒特性，从而改善患者的治疗效果并解决耐药病原体的问题。因此，有必要进行更广泛的研究，以评估将姜黄素纳米乳剂用于幽门螺杆菌治疗的安全性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Helicobacter 医学-微生物学

CiteScore

8.40

自引率

9.10%

发文量

审稿时长

2 months

期刊介绍： Helicobacter is edited by Professor David Y Graham. The editorial and peer review process is an independent process. Whenever there is a conflict of interest, the editor and editorial board will declare their interests and affiliations. Helicobacter recognises the critical role that has been established for Helicobacter pylori in peptic ulcer, gastric adenocarcinoma, and primary gastric lymphoma. As new helicobacter species are now regularly being discovered, Helicobacter covers the entire range of helicobacter research, increasing communication among the fields of gastroenterology; microbiology; vaccine development; laboratory animal science.