The implication of the crosstalk of Nrf2 with NOXs, and HMGB1 in ethanol-induced gastric ulcer: Potential protective effect is afforded by Raspberry Ketone.
Ethanol consumption is one of the common causative agents implicated in gastric ulcer development. Oxidative stress plays a major role in the induction and development of gastric ulceration. NADPH oxidases (NOXs) and Nuclear factor erythroid 2-related factor 2 (Nrf2) are key players in ethanol-induc...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0220548 |
| _version_ | 1819147156447035392 |
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| author | Amira M Badr Naglaa F El-Orabi Rehab A Ali |
| author_facet | Amira M Badr Naglaa F El-Orabi Rehab A Ali |
| author_sort | Amira M Badr |
| collection | DOAJ |
| description | Ethanol consumption is one of the common causative agents implicated in gastric ulcer development. Oxidative stress plays a major role in the induction and development of gastric ulceration. NADPH oxidases (NOXs) and Nuclear factor erythroid 2-related factor 2 (Nrf2) are key players in ethanol-induced ulcers. High-mobility group box 1 (HMGB1), a ubiquitous nuclear protein, mediates various inflammation functions. However, the role of HMGB1 in ethanol-induced gastric ulcer is not yet elucidated. Raspberry Ketone (RK) is a natural phenolic compound with antioxidant and anti-inflammatory properties. In the present study, absolute ethanol (7.5 ml/kg) was used to induce gastric ulceration in rats. Raspberry Ketone (RK) (50 mg/kg) was given orally one hour before the administration of absolute ethanol. Interestingly, ethanol-induced gastric ulcer was associated with Nrf2 downregulation, which was correlated with NOX-1, 2 NOX-4, and HMGB1 upregulation, and was significantly reversed by RK pre-treatment. RK pre-treatment provided 80% gastroprotection. Gastroprotective properties of RK were mediated via antioxidant, anti-inflammatory (suppression of NF-kB and tumor necrosis factor-α), and antiapoptotic activities (reduction of Bax/Bcl2 ratio). Gastroprotective properties of RK were confirmed by histopathological examination. In conclusion, this study is the first to provide evidence to the role of HMGB1 in ethanol-induced gastric ulcer, and the crosstalk of Nrf2, NOXs and HMGB1. It also demonstrates that RK represents a promising gastroprotective activity comparable to omeprazole. |
| first_indexed | 2024-12-22T13:25:20Z |
| format | Article |
| id | doaj.art-c25a2369583a49d6a722e940be164ede |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T13:25:20Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c25a2369583a49d6a722e940be164ede2022-12-21T18:24:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01148e022054810.1371/journal.pone.0220548The implication of the crosstalk of Nrf2 with NOXs, and HMGB1 in ethanol-induced gastric ulcer: Potential protective effect is afforded by Raspberry Ketone.Amira M BadrNaglaa F El-OrabiRehab A AliEthanol consumption is one of the common causative agents implicated in gastric ulcer development. Oxidative stress plays a major role in the induction and development of gastric ulceration. NADPH oxidases (NOXs) and Nuclear factor erythroid 2-related factor 2 (Nrf2) are key players in ethanol-induced ulcers. High-mobility group box 1 (HMGB1), a ubiquitous nuclear protein, mediates various inflammation functions. However, the role of HMGB1 in ethanol-induced gastric ulcer is not yet elucidated. Raspberry Ketone (RK) is a natural phenolic compound with antioxidant and anti-inflammatory properties. In the present study, absolute ethanol (7.5 ml/kg) was used to induce gastric ulceration in rats. Raspberry Ketone (RK) (50 mg/kg) was given orally one hour before the administration of absolute ethanol. Interestingly, ethanol-induced gastric ulcer was associated with Nrf2 downregulation, which was correlated with NOX-1, 2 NOX-4, and HMGB1 upregulation, and was significantly reversed by RK pre-treatment. RK pre-treatment provided 80% gastroprotection. Gastroprotective properties of RK were mediated via antioxidant, anti-inflammatory (suppression of NF-kB and tumor necrosis factor-α), and antiapoptotic activities (reduction of Bax/Bcl2 ratio). Gastroprotective properties of RK were confirmed by histopathological examination. In conclusion, this study is the first to provide evidence to the role of HMGB1 in ethanol-induced gastric ulcer, and the crosstalk of Nrf2, NOXs and HMGB1. It also demonstrates that RK represents a promising gastroprotective activity comparable to omeprazole.https://doi.org/10.1371/journal.pone.0220548 |
| spellingShingle | Amira M Badr Naglaa F El-Orabi Rehab A Ali The implication of the crosstalk of Nrf2 with NOXs, and HMGB1 in ethanol-induced gastric ulcer: Potential protective effect is afforded by Raspberry Ketone. PLoS ONE |
| title | The implication of the crosstalk of Nrf2 with NOXs, and HMGB1 in ethanol-induced gastric ulcer: Potential protective effect is afforded by Raspberry Ketone. |
| title_full | The implication of the crosstalk of Nrf2 with NOXs, and HMGB1 in ethanol-induced gastric ulcer: Potential protective effect is afforded by Raspberry Ketone. |
| title_fullStr | The implication of the crosstalk of Nrf2 with NOXs, and HMGB1 in ethanol-induced gastric ulcer: Potential protective effect is afforded by Raspberry Ketone. |
| title_full_unstemmed | The implication of the crosstalk of Nrf2 with NOXs, and HMGB1 in ethanol-induced gastric ulcer: Potential protective effect is afforded by Raspberry Ketone. |
| title_short | The implication of the crosstalk of Nrf2 with NOXs, and HMGB1 in ethanol-induced gastric ulcer: Potential protective effect is afforded by Raspberry Ketone. |
| title_sort | implication of the crosstalk of nrf2 with noxs and hmgb1 in ethanol induced gastric ulcer potential protective effect is afforded by raspberry ketone |
| url | https://doi.org/10.1371/journal.pone.0220548 |
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