Rhamnetin, a Natural Flavonoid, Ameliorates Organ Damage in a Mouse Model of Carbapenem-Resistant <i>Acinetobacter baumannii</i>-Induced Sepsis
In sepsis, the persistence of uncontrolled inflammatory response of infected host cells eventually leads to severe lung and organ failure and, ultimately, death. Carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB), causative bacteria of sepsis and lung failure in acute cases, belo...
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/21/12895 |
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| author | Hyeju Lee Manigandan Krishnan Minju Kim Young Kyung Yoon Yangmee Kim |
| author_facet | Hyeju Lee Manigandan Krishnan Minju Kim Young Kyung Yoon Yangmee Kim |
| author_sort | Hyeju Lee |
| collection | DOAJ |
| description | In sepsis, the persistence of uncontrolled inflammatory response of infected host cells eventually leads to severe lung and organ failure and, ultimately, death. Carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB), causative bacteria of sepsis and lung failure in acute cases, belongs to a group of critical pathogens that cannot be eradicated using the currently available antibiotics. This underlines the necessity of developing new modes of therapeutics that can control sepsis at the initial stages. In this study, we investigated the anti-inflammatory activities in vitro and in vivo and the antiseptic effects of rhamnetin, a naturally occurring flavonoid. We found that among its isoforms, the potency of rhamnetin was less explored but rhamnetin possessed superior anti-inflammatory activity with least cytotoxicity. Rhamnetin showed significant anti-inflammatory effects in lipopolysaccharide-, CRAB-, and <i>Escherichia coli</i> (<i>E. coli</i>)-stimulated mouse macrophages by inhibiting the release of interleukin-6 and nitric oxide. In a mouse model of sepsis infected with clinically isolated CRAB or <i>E. coli</i>, rhamnetin significantly reduced the bacterial burden in the organs. In addition, normalized pro-inflammatory cytokine levels in lung lysates and histological analysis of lung tissue indicated alleviation of lung damage. This study implies that a potent natural product such as rhamnetin could be a future therapeutic for treating carbapenem-resistant gram-negative sepsis. |
| first_indexed | 2024-03-09T19:01:11Z |
| format | Article |
| id | doaj.art-0012b0a16de44f8a8a54cfda3bc6240f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T19:01:11Z |
| publishDate | 2022-10-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0012b0a16de44f8a8a54cfda3bc6240f2023-11-24T04:58:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123211289510.3390/ijms232112895Rhamnetin, a Natural Flavonoid, Ameliorates Organ Damage in a Mouse Model of Carbapenem-Resistant <i>Acinetobacter baumannii</i>-Induced SepsisHyeju Lee0Manigandan Krishnan1Minju Kim2Young Kyung Yoon3Yangmee Kim4Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, KoreaDepartment of Bioscience and Biotechnology, Konkuk University, Seoul 05029, KoreaDepartment of Bioscience and Biotechnology, Konkuk University, Seoul 05029, KoreaDivision of Infectious Diseases, Department of Internal Medicine, College of Medicine, Korea University Anam Hospital, Korea University, Seoul 02841, KoreaDepartment of Bioscience and Biotechnology, Konkuk University, Seoul 05029, KoreaIn sepsis, the persistence of uncontrolled inflammatory response of infected host cells eventually leads to severe lung and organ failure and, ultimately, death. Carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB), causative bacteria of sepsis and lung failure in acute cases, belongs to a group of critical pathogens that cannot be eradicated using the currently available antibiotics. This underlines the necessity of developing new modes of therapeutics that can control sepsis at the initial stages. In this study, we investigated the anti-inflammatory activities in vitro and in vivo and the antiseptic effects of rhamnetin, a naturally occurring flavonoid. We found that among its isoforms, the potency of rhamnetin was less explored but rhamnetin possessed superior anti-inflammatory activity with least cytotoxicity. Rhamnetin showed significant anti-inflammatory effects in lipopolysaccharide-, CRAB-, and <i>Escherichia coli</i> (<i>E. coli</i>)-stimulated mouse macrophages by inhibiting the release of interleukin-6 and nitric oxide. In a mouse model of sepsis infected with clinically isolated CRAB or <i>E. coli</i>, rhamnetin significantly reduced the bacterial burden in the organs. In addition, normalized pro-inflammatory cytokine levels in lung lysates and histological analysis of lung tissue indicated alleviation of lung damage. This study implies that a potent natural product such as rhamnetin could be a future therapeutic for treating carbapenem-resistant gram-negative sepsis.https://www.mdpi.com/1422-0067/23/21/12895sepsisrhamnetinlung recovery<i>Escherichia coli</i>carbapenem-resistant <i>Acinetobacter baumannii</i> |
| spellingShingle | Hyeju Lee Manigandan Krishnan Minju Kim Young Kyung Yoon Yangmee Kim Rhamnetin, a Natural Flavonoid, Ameliorates Organ Damage in a Mouse Model of Carbapenem-Resistant <i>Acinetobacter baumannii</i>-Induced Sepsis International Journal of Molecular Sciences sepsis rhamnetin lung recovery <i>Escherichia coli</i> carbapenem-resistant <i>Acinetobacter baumannii</i> |
| title | Rhamnetin, a Natural Flavonoid, Ameliorates Organ Damage in a Mouse Model of Carbapenem-Resistant <i>Acinetobacter baumannii</i>-Induced Sepsis |
| title_full | Rhamnetin, a Natural Flavonoid, Ameliorates Organ Damage in a Mouse Model of Carbapenem-Resistant <i>Acinetobacter baumannii</i>-Induced Sepsis |
| title_fullStr | Rhamnetin, a Natural Flavonoid, Ameliorates Organ Damage in a Mouse Model of Carbapenem-Resistant <i>Acinetobacter baumannii</i>-Induced Sepsis |
| title_full_unstemmed | Rhamnetin, a Natural Flavonoid, Ameliorates Organ Damage in a Mouse Model of Carbapenem-Resistant <i>Acinetobacter baumannii</i>-Induced Sepsis |
| title_short | Rhamnetin, a Natural Flavonoid, Ameliorates Organ Damage in a Mouse Model of Carbapenem-Resistant <i>Acinetobacter baumannii</i>-Induced Sepsis |
| title_sort | rhamnetin a natural flavonoid ameliorates organ damage in a mouse model of carbapenem resistant i acinetobacter baumannii i induced sepsis |
| topic | sepsis rhamnetin lung recovery <i>Escherichia coli</i> carbapenem-resistant <i>Acinetobacter baumannii</i> |
| url | https://www.mdpi.com/1422-0067/23/21/12895 |
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