Orientin Alleviates Liver Inflammation via Downregulation of ZEB-2/PTEN Markers—Hepatic Stellate Cells Approach
Liver inflammation is associated with an increased risk of liver fibrosis that substantially progresses to cirrhosis. Recently, usage of the herbal supplement has been increased because of its emerging role to dominate oxidative stress in hepatic injury. Orientin is one of the bioactive flavonoids t...
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MDPI AG
2022-03-01
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| author | Hany Ezzat Khalil Hairul-Islam Mohamed Ibrahim Kareem Ahmed El-Fass Sabah H. Akrawi Mohamed A. Morsy |
| author_facet | Hany Ezzat Khalil Hairul-Islam Mohamed Ibrahim Kareem Ahmed El-Fass Sabah H. Akrawi Mohamed A. Morsy |
| author_sort | Hany Ezzat Khalil |
| collection | DOAJ |
| description | Liver inflammation is associated with an increased risk of liver fibrosis that substantially progresses to cirrhosis. Recently, usage of the herbal supplement has been increased because of its emerging role to dominate oxidative stress in hepatic injury. Orientin is one of the bioactive flavonoids that possesses a diversity of curative activities. Therefore, the present study was conducted to evaluate the anti-inflammatory role of orientin (1 mg/kg) in vitro in lipopolysaccharide (LPS)-induced inflammation in hepatic stellate cells (HSCs) and in vivo in carbon tetrachloride (CCl<sub>4</sub>)-induced liver fibrosis in mice. Moreover, the current study was supported by in silico investigation. Orientin demonstrated protection against LPS-induced HSC inflammation as evidenced by a decrease in iNOS, NO, and TNF-α and inhibition of the fibrotic markers ZEB-2 and PTEN. In addition, orientin afforded protection against CCl<sub>4</sub>-induced liver fibrosis in mice as shown from decreased AST/ALT ratio, inhibition of the pro-inflammatory mediators TNF-α, IL-6, IL-8, and IFN-γ, reduction of fibrotic markers ZEB-2 and PTEN, and improvement of the histopathological changes. Furthermore, the docking study demonstrated virtual interactions of orientin with ZEB-2 and PTEN. Taken together, the current study suggested that the protective effects of orientin against LPS- and CCl<sub>4</sub>-induced liver inflammation are via inhibition of fibrotic markers and reduction of pro-inflammatory mediators. |
| first_indexed | 2024-03-09T20:47:07Z |
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| institution | Directory Open Access Journal |
| issn | 2076-3417 |
| language | English |
| last_indexed | 2024-03-09T20:47:07Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Applied Sciences |
| spelling | doaj.art-d855068e1d86453eaf347326f3e7a0cd2023-11-23T22:45:20ZengMDPI AGApplied Sciences2076-34172022-03-01125272510.3390/app12052725Orientin Alleviates Liver Inflammation via Downregulation of ZEB-2/PTEN Markers—Hepatic Stellate Cells ApproachHany Ezzat Khalil0Hairul-Islam Mohamed Ibrahim1Kareem Ahmed El-Fass2Sabah H. Akrawi3Mohamed A. Morsy4Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Biological Sciences, College of Science, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmacy Practice, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaLiver inflammation is associated with an increased risk of liver fibrosis that substantially progresses to cirrhosis. Recently, usage of the herbal supplement has been increased because of its emerging role to dominate oxidative stress in hepatic injury. Orientin is one of the bioactive flavonoids that possesses a diversity of curative activities. Therefore, the present study was conducted to evaluate the anti-inflammatory role of orientin (1 mg/kg) in vitro in lipopolysaccharide (LPS)-induced inflammation in hepatic stellate cells (HSCs) and in vivo in carbon tetrachloride (CCl<sub>4</sub>)-induced liver fibrosis in mice. Moreover, the current study was supported by in silico investigation. Orientin demonstrated protection against LPS-induced HSC inflammation as evidenced by a decrease in iNOS, NO, and TNF-α and inhibition of the fibrotic markers ZEB-2 and PTEN. In addition, orientin afforded protection against CCl<sub>4</sub>-induced liver fibrosis in mice as shown from decreased AST/ALT ratio, inhibition of the pro-inflammatory mediators TNF-α, IL-6, IL-8, and IFN-γ, reduction of fibrotic markers ZEB-2 and PTEN, and improvement of the histopathological changes. Furthermore, the docking study demonstrated virtual interactions of orientin with ZEB-2 and PTEN. Taken together, the current study suggested that the protective effects of orientin against LPS- and CCl<sub>4</sub>-induced liver inflammation are via inhibition of fibrotic markers and reduction of pro-inflammatory mediators.https://www.mdpi.com/2076-3417/12/5/2725orientinZEB-2PTENTNF-αiNOShepatic stellate cells |
| spellingShingle | Hany Ezzat Khalil Hairul-Islam Mohamed Ibrahim Kareem Ahmed El-Fass Sabah H. Akrawi Mohamed A. Morsy Orientin Alleviates Liver Inflammation via Downregulation of ZEB-2/PTEN Markers—Hepatic Stellate Cells Approach Applied Sciences orientin ZEB-2 PTEN TNF-α iNOS hepatic stellate cells |
| title | Orientin Alleviates Liver Inflammation via Downregulation of ZEB-2/PTEN Markers—Hepatic Stellate Cells Approach |
| title_full | Orientin Alleviates Liver Inflammation via Downregulation of ZEB-2/PTEN Markers—Hepatic Stellate Cells Approach |
| title_fullStr | Orientin Alleviates Liver Inflammation via Downregulation of ZEB-2/PTEN Markers—Hepatic Stellate Cells Approach |
| title_full_unstemmed | Orientin Alleviates Liver Inflammation via Downregulation of ZEB-2/PTEN Markers—Hepatic Stellate Cells Approach |
| title_short | Orientin Alleviates Liver Inflammation via Downregulation of ZEB-2/PTEN Markers—Hepatic Stellate Cells Approach |
| title_sort | orientin alleviates liver inflammation via downregulation of zeb 2 pten markers hepatic stellate cells approach |
| topic | orientin ZEB-2 PTEN TNF-α iNOS hepatic stellate cells |
| url | https://www.mdpi.com/2076-3417/12/5/2725 |
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