Anti‐microbial efficacy, mechanisms and druggability evaluation of the natural flavonoids
Aims This study was conducted to evaluate 35 natural flavonoids for their in vitro susceptibility against E. coli (ATCC 25922), Ps. aeruginosa (ATCC 27853), B. subtilis (ATCC 530) and Staph. aureus (ATCC 6538) in search of a potential broad‐spectrum antibiotic. Methods and Results Glabridin, a natur...
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| Veröffentlicht in: | Journal of applied microbiology 2022-09, Vol.133 (3), p.1975-1988 |
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| container_end_page | 1988 |
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| container_issue | 3 |
| container_start_page | 1975 |
| container_title | Journal of applied microbiology |
| container_volume | 133 |
| creator | Lin, Hongyan Hu, Jiabao Mei, Feng Zhang, Yahan Ma, Yudi Chen, Qingqing Wang, Changyi Fu, Jiangyan Yang, Minkai Wen, Zhongling Wang, Xiaoming Qi, Jinliang Han, Hongwei Yang, Rongwu Yang, Yonghua |
| description | Aims
This study was conducted to evaluate 35 natural flavonoids for their in vitro susceptibility against E. coli (ATCC 25922), Ps. aeruginosa (ATCC 27853), B. subtilis (ATCC 530) and Staph. aureus (ATCC 6538) in search of a potential broad‐spectrum antibiotic.
Methods and Results
Glabridin, a natural isoflavonoid isolated from Glycyrrhiza glabra L., was identified to be highly active with a MIC of 8–16 μg ml−1 against Staph. aureus, B. subtilis and E. coli. By the results of the docking simulation, we located the potential targets of glabridin as DNA gyrase and dihydrofolate reductase (DHFR). The subsequent DNA gyrase inhibition assays (glabridin: IC50 = 0.8516 μmol L−1, ciprofloxacin: IC50 = 0.04697 μmol L−1), DHFR inhibition assays (glabridin: inhibition ratio = 29%, methotrexate: inhibition ratio = 45% under 100 μmol L−1 treatment) and TUNEL confirmed that glabridin acted as DNA gyrase inhibitor and DHFR mild inhibitor, exerting bactericidal activity by blocking bacterial nucleic acid synthesis. CCK‐8 and in silico calculations were also conducted to verify the low cytotoxicity and acceptable druggability of glabridin.
Conclusion
These findings suggest that glabridin represents the prototypical member of an exciting structural class of natural antimicrobial agents.
Significance and Impact of the Study
This study reports a novel mechanism of bactericidal activity of glabridin against Staph. aureus. |
| doi_str_mv | 10.1111/jam.15705 |
| format | Article |
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This study was conducted to evaluate 35 natural flavonoids for their in vitro susceptibility against E. coli (ATCC 25922), Ps. aeruginosa (ATCC 27853), B. subtilis (ATCC 530) and Staph. aureus (ATCC 6538) in search of a potential broad‐spectrum antibiotic.
Methods and Results
Glabridin, a natural isoflavonoid isolated from Glycyrrhiza glabra L., was identified to be highly active with a MIC of 8–16 μg ml−1 against Staph. aureus, B. subtilis and E. coli. By the results of the docking simulation, we located the potential targets of glabridin as DNA gyrase and dihydrofolate reductase (DHFR). The subsequent DNA gyrase inhibition assays (glabridin: IC50 = 0.8516 μmol L−1, ciprofloxacin: IC50 = 0.04697 μmol L−1), DHFR inhibition assays (glabridin: inhibition ratio = 29%, methotrexate: inhibition ratio = 45% under 100 μmol L−1 treatment) and TUNEL confirmed that glabridin acted as DNA gyrase inhibitor and DHFR mild inhibitor, exerting bactericidal activity by blocking bacterial nucleic acid synthesis. CCK‐8 and in silico calculations were also conducted to verify the low cytotoxicity and acceptable druggability of glabridin.
Conclusion
These findings suggest that glabridin represents the prototypical member of an exciting structural class of natural antimicrobial agents.
Significance and Impact of the Study
This study reports a novel mechanism of bactericidal activity of glabridin against Staph. aureus.</description><identifier>ISSN: 1364-5072</identifier><identifier>EISSN: 1365-2672</identifier><identifier>DOI: 10.1111/jam.15705</identifier><language>eng</language><publisher>Cambridge: Oxford University Press</publisher><subject>Antibiotics ; Antiinfectives and antibacterials ; Antimicrobial agents ; Bactericidal activity ; Cholecystokinin ; Ciprofloxacin ; Cytotoxicity ; Deoxyribonucleic acid ; Dihydrofolate reductase ; DNA ; DNA gyrase ; DNA topoisomerase ; E coli ; Flavonoids ; glabridin ; Inhibitors ; Methotrexate ; Microorganisms ; Minimum inhibitory concentration ; Nucleic acids ; Reductases ; Staph. aureus ; Toxicity</subject><ispartof>Journal of applied microbiology, 2022-09, Vol.133 (3), p.1975-1988</ispartof><rights>2022 Society for Applied Microbiology.</rights><rights>Copyright © 2022 The Society for Applied Microbiology</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3305-50f5373e8e602bd4d7cc226b19f517084f764e4e3cfe623985a54f13c6f2986b3</citedby><cites>FETCH-LOGICAL-c3305-50f5373e8e602bd4d7cc226b19f517084f764e4e3cfe623985a54f13c6f2986b3</cites><orcidid>0000-0002-8647-1158</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%2Fjam.15705$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjam.15705$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids></links><search><creatorcontrib>Lin, Hongyan</creatorcontrib><creatorcontrib>Hu, Jiabao</creatorcontrib><creatorcontrib>Mei, Feng</creatorcontrib><creatorcontrib>Zhang, Yahan</creatorcontrib><creatorcontrib>Ma, Yudi</creatorcontrib><creatorcontrib>Chen, Qingqing</creatorcontrib><creatorcontrib>Wang, Changyi</creatorcontrib><creatorcontrib>Fu, Jiangyan</creatorcontrib><creatorcontrib>Yang, Minkai</creatorcontrib><creatorcontrib>Wen, Zhongling</creatorcontrib><creatorcontrib>Wang, Xiaoming</creatorcontrib><creatorcontrib>Qi, Jinliang</creatorcontrib><creatorcontrib>Han, Hongwei</creatorcontrib><creatorcontrib>Yang, Rongwu</creatorcontrib><creatorcontrib>Yang, Yonghua</creatorcontrib><title>Anti‐microbial efficacy, mechanisms and druggability evaluation of the natural flavonoids</title><title>Journal of applied microbiology</title><description>Aims
This study was conducted to evaluate 35 natural flavonoids for their in vitro susceptibility against E. coli (ATCC 25922), Ps. aeruginosa (ATCC 27853), B. subtilis (ATCC 530) and Staph. aureus (ATCC 6538) in search of a potential broad‐spectrum antibiotic.
Methods and Results
Glabridin, a natural isoflavonoid isolated from Glycyrrhiza glabra L., was identified to be highly active with a MIC of 8–16 μg ml−1 against Staph. aureus, B. subtilis and E. coli. By the results of the docking simulation, we located the potential targets of glabridin as DNA gyrase and dihydrofolate reductase (DHFR). The subsequent DNA gyrase inhibition assays (glabridin: IC50 = 0.8516 μmol L−1, ciprofloxacin: IC50 = 0.04697 μmol L−1), DHFR inhibition assays (glabridin: inhibition ratio = 29%, methotrexate: inhibition ratio = 45% under 100 μmol L−1 treatment) and TUNEL confirmed that glabridin acted as DNA gyrase inhibitor and DHFR mild inhibitor, exerting bactericidal activity by blocking bacterial nucleic acid synthesis. CCK‐8 and in silico calculations were also conducted to verify the low cytotoxicity and acceptable druggability of glabridin.
Conclusion
These findings suggest that glabridin represents the prototypical member of an exciting structural class of natural antimicrobial agents.
Significance and Impact of the Study
This study reports a novel mechanism of bactericidal activity of glabridin against Staph. aureus.</description><subject>Antibiotics</subject><subject>Antiinfectives and antibacterials</subject><subject>Antimicrobial agents</subject><subject>Bactericidal activity</subject><subject>Cholecystokinin</subject><subject>Ciprofloxacin</subject><subject>Cytotoxicity</subject><subject>Deoxyribonucleic acid</subject><subject>Dihydrofolate reductase</subject><subject>DNA</subject><subject>DNA gyrase</subject><subject>DNA topoisomerase</subject><subject>E coli</subject><subject>Flavonoids</subject><subject>glabridin</subject><subject>Inhibitors</subject><subject>Methotrexate</subject><subject>Microorganisms</subject><subject>Minimum inhibitory concentration</subject><subject>Nucleic acids</subject><subject>Reductases</subject><subject>Staph. aureus</subject><subject>Toxicity</subject><issn>1364-5072</issn><issn>1365-2672</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp1kLtOwzAUhiMEEqUw8AaRWEAirS-xnYxVxVUgFpgYLMexW1eOXeKkKBuPwDPyJJiWCYmznDN8_9GvL0lOIZjAONOVaCaQMED2khHElGSIMrS_vfOMAIYOk6MQVgBADAgdJa8z15mvj8_GyNZXRthUaW2kkMNl2ii5FM6EJqTC1Wnd9ouFqIw13ZCqjbC96Ix3qddpt1SpE13fxry2YuOdN3U4Tg60sEGd_O5x8nJ99Ty_zR6ebu7ms4dM4lgittIEM6wKRQGq6rxmUiJEK1hqAhkocs1ornKFpVYU4bIgguQaYkk1Kgta4XFyvvu7bv1br0LHGxOkslY45fvAES0YgyUhKKJnf9CV71sX23HEQFkUFFEaqYsdFZ2E0CrN161pRDtwCPiPZh41863myE537Luxavgf5Pezx13iG-S4fx4</recordid><startdate>202209</startdate><enddate>202209</enddate><creator>Lin, Hongyan</creator><creator>Hu, Jiabao</creator><creator>Mei, Feng</creator><creator>Zhang, Yahan</creator><creator>Ma, Yudi</creator><creator>Chen, Qingqing</creator><creator>Wang, Changyi</creator><creator>Fu, Jiangyan</creator><creator>Yang, Minkai</creator><creator>Wen, Zhongling</creator><creator>Wang, Xiaoming</creator><creator>Qi, Jinliang</creator><creator>Han, Hongwei</creator><creator>Yang, Rongwu</creator><creator>Yang, Yonghua</creator><general>Oxford University Press</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QO</scope><scope>7T7</scope><scope>7TM</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-8647-1158</orcidid></search><sort><creationdate>202209</creationdate><title>Anti‐microbial efficacy, mechanisms and druggability evaluation of the natural flavonoids</title><author>Lin, Hongyan ; Hu, Jiabao ; Mei, Feng ; Zhang, Yahan ; Ma, Yudi ; Chen, Qingqing ; Wang, Changyi ; Fu, Jiangyan ; Yang, Minkai ; Wen, Zhongling ; Wang, Xiaoming ; Qi, Jinliang ; Han, Hongwei ; Yang, Rongwu ; Yang, Yonghua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3305-50f5373e8e602bd4d7cc226b19f517084f764e4e3cfe623985a54f13c6f2986b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Antibiotics</topic><topic>Antiinfectives and antibacterials</topic><topic>Antimicrobial agents</topic><topic>Bactericidal activity</topic><topic>Cholecystokinin</topic><topic>Ciprofloxacin</topic><topic>Cytotoxicity</topic><topic>Deoxyribonucleic acid</topic><topic>Dihydrofolate reductase</topic><topic>DNA</topic><topic>DNA gyrase</topic><topic>DNA topoisomerase</topic><topic>E coli</topic><topic>Flavonoids</topic><topic>glabridin</topic><topic>Inhibitors</topic><topic>Methotrexate</topic><topic>Microorganisms</topic><topic>Minimum inhibitory concentration</topic><topic>Nucleic acids</topic><topic>Reductases</topic><topic>Staph. aureus</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lin, Hongyan</creatorcontrib><creatorcontrib>Hu, Jiabao</creatorcontrib><creatorcontrib>Mei, Feng</creatorcontrib><creatorcontrib>Zhang, Yahan</creatorcontrib><creatorcontrib>Ma, Yudi</creatorcontrib><creatorcontrib>Chen, Qingqing</creatorcontrib><creatorcontrib>Wang, Changyi</creatorcontrib><creatorcontrib>Fu, Jiangyan</creatorcontrib><creatorcontrib>Yang, Minkai</creatorcontrib><creatorcontrib>Wen, Zhongling</creatorcontrib><creatorcontrib>Wang, Xiaoming</creatorcontrib><creatorcontrib>Qi, Jinliang</creatorcontrib><creatorcontrib>Han, Hongwei</creatorcontrib><creatorcontrib>Yang, Rongwu</creatorcontrib><creatorcontrib>Yang, Yonghua</creatorcontrib><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of applied microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lin, Hongyan</au><au>Hu, Jiabao</au><au>Mei, Feng</au><au>Zhang, Yahan</au><au>Ma, Yudi</au><au>Chen, Qingqing</au><au>Wang, Changyi</au><au>Fu, Jiangyan</au><au>Yang, Minkai</au><au>Wen, Zhongling</au><au>Wang, Xiaoming</au><au>Qi, Jinliang</au><au>Han, Hongwei</au><au>Yang, Rongwu</au><au>Yang, Yonghua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anti‐microbial efficacy, mechanisms and druggability evaluation of the natural flavonoids</atitle><jtitle>Journal of applied microbiology</jtitle><date>2022-09</date><risdate>2022</risdate><volume>133</volume><issue>3</issue><spage>1975</spage><epage>1988</epage><pages>1975-1988</pages><issn>1364-5072</issn><eissn>1365-2672</eissn><abstract>Aims
This study was conducted to evaluate 35 natural flavonoids for their in vitro susceptibility against E. coli (ATCC 25922), Ps. aeruginosa (ATCC 27853), B. subtilis (ATCC 530) and Staph. aureus (ATCC 6538) in search of a potential broad‐spectrum antibiotic.
Methods and Results
Glabridin, a natural isoflavonoid isolated from Glycyrrhiza glabra L., was identified to be highly active with a MIC of 8–16 μg ml−1 against Staph. aureus, B. subtilis and E. coli. By the results of the docking simulation, we located the potential targets of glabridin as DNA gyrase and dihydrofolate reductase (DHFR). The subsequent DNA gyrase inhibition assays (glabridin: IC50 = 0.8516 μmol L−1, ciprofloxacin: IC50 = 0.04697 μmol L−1), DHFR inhibition assays (glabridin: inhibition ratio = 29%, methotrexate: inhibition ratio = 45% under 100 μmol L−1 treatment) and TUNEL confirmed that glabridin acted as DNA gyrase inhibitor and DHFR mild inhibitor, exerting bactericidal activity by blocking bacterial nucleic acid synthesis. CCK‐8 and in silico calculations were also conducted to verify the low cytotoxicity and acceptable druggability of glabridin.
Conclusion
These findings suggest that glabridin represents the prototypical member of an exciting structural class of natural antimicrobial agents.
Significance and Impact of the Study
This study reports a novel mechanism of bactericidal activity of glabridin against Staph. aureus.</abstract><cop>Cambridge</cop><pub>Oxford University Press</pub><doi>10.1111/jam.15705</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-8647-1158</orcidid></addata></record> |
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| identifier | ISSN: 1364-5072 |
| ispartof | Journal of applied microbiology, 2022-09, Vol.133 (3), p.1975-1988 |
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| source | Wiley Online Library Journals Frontfile Complete; Oxford University Press Journals All Titles (1996-Current) |
| subjects | Antibiotics Antiinfectives and antibacterials Antimicrobial agents Bactericidal activity Cholecystokinin Ciprofloxacin Cytotoxicity Deoxyribonucleic acid Dihydrofolate reductase DNA DNA gyrase DNA topoisomerase E coli Flavonoids glabridin Inhibitors Methotrexate Microorganisms Minimum inhibitory concentration Nucleic acids Reductases Staph. aureus Toxicity |
| title | Anti‐microbial efficacy, mechanisms and druggability evaluation of the natural flavonoids |
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