Boosting the Anti‐Helicobacter Efficacy of Azithromycin through Natural Compounds: Insights From In Vitro, In Vivo, Histopathological, and Molecular Docking Investigations
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 dim...
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| Veröffentlicht in: | Helicobacter (Cambridge, Mass.) Mass.), 2024-07, Vol.29 (4), p.e13110-n/a |
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| creator | 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 |
| description | 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 |
| doi_str_mv | 10.1111/hel.13110 |
| format | Article |
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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.</description><identifier>ISSN: 1083-4389</identifier><identifier>ISSN: 1523-5378</identifier><identifier>EISSN: 1523-5378</identifier><identifier>DOI: 10.1111/hel.13110</identifier><identifier>PMID: 39001634</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Animals ; Anti-Bacterial Agents - chemistry ; Anti-Bacterial Agents - pharmacology ; Antibiotics ; anti‐biofilm ; anti‐Helicobacter ; anti‐virulence ; Azithromycin ; Azithromycin - chemistry ; Azithromycin - pharmacology ; Biofilms ; Biofilms - drug effects ; Biological Products - chemistry ; Biological Products - pharmacology ; Curcumin ; Curcumin - chemistry ; Curcumin - pharmacology ; curcumin nanoemulsion ; Drug development ; Drug Synergism ; Effectiveness ; Emulsions ; Female ; FICI ; Formulations ; Genes ; H. pylori ; Helicobacter ; Helicobacter Infections - drug therapy ; Helicobacter Infections - microbiology ; Helicobacter pylori - drug effects ; Helicobacter pylori - genetics ; In vivo methods and tests ; Mice ; Microbial Sensitivity Tests ; Minimum inhibitory concentration ; Molecular docking ; Molecular Docking Simulation ; Nanoemulsions ; Protein folding ; Public health ; Strains (organisms) ; Synergistic effect ; Urea ; Virulence ; Virulence - drug effects</subject><ispartof>Helicobacter (Cambridge, Mass.), 2024-07, Vol.29 (4), p.e13110-n/a</ispartof><rights>2024 John Wiley & Sons Ltd.</rights><rights>Copyright © 2024 John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2430-aa588130e70cf8a2146a32b2ffbcdfef235c52e8bf8001e2b2bec967f02b20c63</cites><orcidid>0000-0003-4930-792X ; 0000-0002-1788-0038</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fhel.13110$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fhel.13110$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39001634$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bendary, Mahmoud M.</creatorcontrib><creatorcontrib>Elmanakhly, Arwa R.</creatorcontrib><creatorcontrib>Mosallam, Farag M.</creatorcontrib><creatorcontrib>Alblwi, Noaf Abdullah N.</creatorcontrib><creatorcontrib>Mosbah, Rasha A.</creatorcontrib><creatorcontrib>Alshareef, Walaa A.</creatorcontrib><creatorcontrib>Selim, Heba M. R. M.</creatorcontrib><creatorcontrib>Alhomrani, Majid</creatorcontrib><creatorcontrib>Alamri, Abdulhakeem S.</creatorcontrib><creatorcontrib>Safwat, Nesreen A.</creatorcontrib><creatorcontrib>Hamdan, Ahmed M. E.</creatorcontrib><creatorcontrib>Elshimy, Rana</creatorcontrib><title>Boosting the Anti‐Helicobacter Efficacy of Azithromycin through Natural Compounds: Insights From In Vitro, In Vivo, Histopathological, and Molecular Docking Investigations</title><title>Helicobacter (Cambridge, Mass.)</title><addtitle>Helicobacter</addtitle><description>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.</description><subject>Animals</subject><subject>Anti-Bacterial Agents - chemistry</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Antibiotics</subject><subject>anti‐biofilm</subject><subject>anti‐Helicobacter</subject><subject>anti‐virulence</subject><subject>Azithromycin</subject><subject>Azithromycin - chemistry</subject><subject>Azithromycin - pharmacology</subject><subject>Biofilms</subject><subject>Biofilms - drug effects</subject><subject>Biological Products - chemistry</subject><subject>Biological Products - pharmacology</subject><subject>Curcumin</subject><subject>Curcumin - chemistry</subject><subject>Curcumin - pharmacology</subject><subject>curcumin nanoemulsion</subject><subject>Drug development</subject><subject>Drug Synergism</subject><subject>Effectiveness</subject><subject>Emulsions</subject><subject>Female</subject><subject>FICI</subject><subject>Formulations</subject><subject>Genes</subject><subject>H. pylori</subject><subject>Helicobacter</subject><subject>Helicobacter Infections - drug therapy</subject><subject>Helicobacter Infections - microbiology</subject><subject>Helicobacter pylori - drug effects</subject><subject>Helicobacter pylori - genetics</subject><subject>In vivo methods and tests</subject><subject>Mice</subject><subject>Microbial Sensitivity Tests</subject><subject>Minimum inhibitory concentration</subject><subject>Molecular docking</subject><subject>Molecular Docking Simulation</subject><subject>Nanoemulsions</subject><subject>Protein folding</subject><subject>Public health</subject><subject>Strains (organisms)</subject><subject>Synergistic effect</subject><subject>Urea</subject><subject>Virulence</subject><subject>Virulence - drug effects</subject><issn>1083-4389</issn><issn>1523-5378</issn><issn>1523-5378</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU-O0zAYxS0EYoaBBRdAltiANJmx4_xx2JXSoZUKbIBt5Lh24sGxi-0MKiuOwBG4AXfgKJyEr7SwQMIbP-v76fnpewg9pOSCwrkclL2gjFJyC53SMmdZyWp-GzThLCsYb07QvRivCSElK5q76IQ1hNCKFafo-3PvYzKux2lQeOaS-fnl61JZI30nZFIBL7Q2Usgd9hrPPps0BD_upHF4r6Z-wK9FmoKweO7HrZ_cJj7DKxdNP6SIrwCG149v700K_vwob0AtTUx-K9Lgre_hA3uOhdvgV94qOVkR8AsvP-xzrdyNgoS9SMa7eB_d0cJG9eB4n6F3V4u382W2fvNyNZ-tM5kXjGRClJxTRlRNpOYip0UlWN7lWndyo5XOWSnLXPFOc9iEgkmnZFPVmoAksmJn6MnBdxv8xwkCtKOJUlkrnPJTbBmpG14Rwgigj_9Br_0UHKQDqqmrsq4pB-rpgZLBxxiUbrfBjCLsWkrafYsttNj-bhHYR0fHqRvV5i_5pzYALg_AJ2PV7v9O7XKxPlj-Akgvq5s</recordid><startdate>202407</startdate><enddate>202407</enddate><creator>Bendary, Mahmoud M.</creator><creator>Elmanakhly, Arwa R.</creator><creator>Mosallam, Farag M.</creator><creator>Alblwi, Noaf Abdullah N.</creator><creator>Mosbah, Rasha A.</creator><creator>Alshareef, Walaa A.</creator><creator>Selim, Heba M. R. M.</creator><creator>Alhomrani, Majid</creator><creator>Alamri, Abdulhakeem S.</creator><creator>Safwat, Nesreen A.</creator><creator>Hamdan, Ahmed M. E.</creator><creator>Elshimy, Rana</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>C1K</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4930-792X</orcidid><orcidid>https://orcid.org/0000-0002-1788-0038</orcidid></search><sort><creationdate>202407</creationdate><title>Boosting the Anti‐Helicobacter Efficacy of Azithromycin through Natural Compounds: Insights From In Vitro, In Vivo, Histopathological, and Molecular Docking Investigations</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2430-aa588130e70cf8a2146a32b2ffbcdfef235c52e8bf8001e2b2bec967f02b20c63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>Anti-Bacterial Agents - chemistry</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Antibiotics</topic><topic>anti‐biofilm</topic><topic>anti‐Helicobacter</topic><topic>anti‐virulence</topic><topic>Azithromycin</topic><topic>Azithromycin - chemistry</topic><topic>Azithromycin - pharmacology</topic><topic>Biofilms</topic><topic>Biofilms - drug effects</topic><topic>Biological Products - chemistry</topic><topic>Biological Products - pharmacology</topic><topic>Curcumin</topic><topic>Curcumin - chemistry</topic><topic>Curcumin - pharmacology</topic><topic>curcumin nanoemulsion</topic><topic>Drug development</topic><topic>Drug Synergism</topic><topic>Effectiveness</topic><topic>Emulsions</topic><topic>Female</topic><topic>FICI</topic><topic>Formulations</topic><topic>Genes</topic><topic>H. pylori</topic><topic>Helicobacter</topic><topic>Helicobacter Infections - drug therapy</topic><topic>Helicobacter Infections - microbiology</topic><topic>Helicobacter pylori - drug effects</topic><topic>Helicobacter pylori - genetics</topic><topic>In vivo methods and tests</topic><topic>Mice</topic><topic>Microbial Sensitivity Tests</topic><topic>Minimum inhibitory concentration</topic><topic>Molecular docking</topic><topic>Molecular Docking Simulation</topic><topic>Nanoemulsions</topic><topic>Protein folding</topic><topic>Public health</topic><topic>Strains (organisms)</topic><topic>Synergistic effect</topic><topic>Urea</topic><topic>Virulence</topic><topic>Virulence - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bendary, Mahmoud M.</creatorcontrib><creatorcontrib>Elmanakhly, Arwa R.</creatorcontrib><creatorcontrib>Mosallam, Farag M.</creatorcontrib><creatorcontrib>Alblwi, Noaf Abdullah N.</creatorcontrib><creatorcontrib>Mosbah, Rasha A.</creatorcontrib><creatorcontrib>Alshareef, Walaa A.</creatorcontrib><creatorcontrib>Selim, Heba M. R. M.</creatorcontrib><creatorcontrib>Alhomrani, Majid</creatorcontrib><creatorcontrib>Alamri, Abdulhakeem S.</creatorcontrib><creatorcontrib>Safwat, Nesreen A.</creatorcontrib><creatorcontrib>Hamdan, Ahmed M. E.</creatorcontrib><creatorcontrib>Elshimy, Rana</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Helicobacter (Cambridge, Mass.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bendary, Mahmoud M.</au><au>Elmanakhly, Arwa R.</au><au>Mosallam, Farag M.</au><au>Alblwi, Noaf Abdullah N.</au><au>Mosbah, Rasha A.</au><au>Alshareef, Walaa A.</au><au>Selim, Heba M. R. M.</au><au>Alhomrani, Majid</au><au>Alamri, Abdulhakeem S.</au><au>Safwat, Nesreen A.</au><au>Hamdan, Ahmed M. E.</au><au>Elshimy, Rana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Boosting the Anti‐Helicobacter Efficacy of Azithromycin through Natural Compounds: Insights From In Vitro, In Vivo, Histopathological, and Molecular Docking Investigations</atitle><jtitle>Helicobacter (Cambridge, Mass.)</jtitle><addtitle>Helicobacter</addtitle><date>2024-07</date><risdate>2024</risdate><volume>29</volume><issue>4</issue><spage>e13110</spage><epage>n/a</epage><pages>e13110-n/a</pages><issn>1083-4389</issn><issn>1523-5378</issn><eissn>1523-5378</eissn><abstract>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.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>39001634</pmid><doi>10.1111/hel.13110</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-4930-792X</orcidid><orcidid>https://orcid.org/0000-0002-1788-0038</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1083-4389 |
| ispartof | Helicobacter (Cambridge, Mass.), 2024-07, Vol.29 (4), p.e13110-n/a |
| issn | 1083-4389 1523-5378 1523-5378 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Animals Anti-Bacterial Agents - chemistry Anti-Bacterial Agents - pharmacology Antibiotics anti‐biofilm anti‐Helicobacter anti‐virulence Azithromycin Azithromycin - chemistry Azithromycin - pharmacology Biofilms Biofilms - drug effects Biological Products - chemistry Biological Products - pharmacology Curcumin Curcumin - chemistry Curcumin - pharmacology curcumin nanoemulsion Drug development Drug Synergism Effectiveness Emulsions Female FICI Formulations Genes H. pylori Helicobacter Helicobacter Infections - drug therapy Helicobacter Infections - microbiology Helicobacter pylori - drug effects Helicobacter pylori - genetics In vivo methods and tests Mice Microbial Sensitivity Tests Minimum inhibitory concentration Molecular docking Molecular Docking Simulation Nanoemulsions Protein folding Public health Strains (organisms) Synergistic effect Urea Virulence Virulence - drug effects |
| title | Boosting the Anti‐Helicobacter Efficacy of Azithromycin through Natural Compounds: Insights From In Vitro, In Vivo, Histopathological, and Molecular Docking Investigations |
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