Rosavin Ameliorates Hepatic Inflammation and Fibrosis in the NASH Rat Model via Targeting Hepatic Cell Death
Background: Non-alcoholic fatty liver disease (NAFLD) represents the most common form of chronic liver disease that urgently needs effective therapy. Rosavin, a major constituent of the Rhodiola Rosea plant of the family Crassulaceae, is believed to exhibit multiple pharmacological effects on divers...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-09-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/17/10148 |
| _version_ | 1797494952366702592 |
|---|---|
| author | Reda Albadawy Amany Helmy Hasanin Sara H. A. Agwa Shaimaa Hamady Yasmin M. Aboul-Ela Mona Hussien Raafat Samaa Samir Kamar Mohamed Othman Yahia A. Yahia Marwa Matboli |
| author_facet | Reda Albadawy Amany Helmy Hasanin Sara H. A. Agwa Shaimaa Hamady Yasmin M. Aboul-Ela Mona Hussien Raafat Samaa Samir Kamar Mohamed Othman Yahia A. Yahia Marwa Matboli |
| author_sort | Reda Albadawy |
| collection | DOAJ |
| description | Background: Non-alcoholic fatty liver disease (NAFLD) represents the most common form of chronic liver disease that urgently needs effective therapy. Rosavin, a major constituent of the Rhodiola Rosea plant of the family Crassulaceae, is believed to exhibit multiple pharmacological effects on diverse diseases. However, its effect on non-alcoholic steatohepatitis (NASH), the progressive form of NAFLD, and the underlying mechanisms are not fully illustrated. Aim: Investigate the pharmacological activity and potential mechanism of rosavin treatment on NASH management via targeting hepatic cell death-related (<i>HSPD1/TNF/MMP14/ITGB1</i>) mRNAs and their upstream noncoding RNA regulators (<i>miRNA-6881-5P</i> and <i>lnc-SPARCL1-1:2</i>) in NASH rats. Results: High sucrose high fat (HSHF) diet-induced NASH rats were treated with different concentrations of rosavin (10, 20, and 30 mg/kg/day) for the last four weeks of dietary manipulation. The data revealed that rosavin had the ability to modulate the expression of the hepatic cell death-related RNA panel through the upregulation of both (<i>HSPD1/TNF/MMP14/ITGB1</i>) mRNAs and their epigenetic regulators (<i>miRNA-6881-5P</i> and <i>lnc-SPARCL1-1:2</i>). Moreover, rosavin ameliorated the deterioration in both liver functions and lipid profile, and thereby improved the hepatic inflammation, fibrosis, and apoptosis, as evidenced by the decreased protein levels of IL6, TNF-α, and caspase-3 in liver sections of treated animals compared to the untreated NASH rats. Conclusion: Rosavin has demonstrated a potential ability to attenuate disease progression and inhibit hepatic cell death in the NASH animal model. The produced effect was correlated with upregulation of the hepatic cell death-related (<i>HSPD1</i>, <i>TNF</i>, <i>MMP14</i>, and <i>ITGB1</i>) mRNAs—(<i>miRNA-6881-5P</i>—(<i>lnc-SPARCL1-1:2</i>) RNA panel. |
| first_indexed | 2024-03-10T01:41:37Z |
| format | Article |
| id | doaj.art-acd03787c0ef4152926f9fbe94fc208d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T01:41:37Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-acd03787c0ef4152926f9fbe94fc208d2023-11-23T13:23:49ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123171014810.3390/ijms231710148Rosavin Ameliorates Hepatic Inflammation and Fibrosis in the NASH Rat Model via Targeting Hepatic Cell DeathReda Albadawy0Amany Helmy Hasanin1Sara H. A. Agwa2Shaimaa Hamady3Yasmin M. Aboul-Ela4Mona Hussien Raafat5Samaa Samir Kamar6Mohamed Othman7Yahia A. Yahia8Marwa Matboli9Department of Gastroenterology, Hepatology & Infectious Disease, Faculty of Medicine, Benha University, Benha 13518, EgyptClinical Pharmacology Department, Faculty of Medicine, Ain Shams University, Cairo 11566, EgyptClinical Pathology and Molecular Genomics Unit, Medical Ain Shams Research Institute (MASRI), Faculty of Medicine, Ain Shams University, Cairo 11382, EgyptDepartment of Biochemistry, Faculty of Science, Ain Shams University, Cairo 11566, EgyptClinical Pharmacology Department, Faculty of Medicine, Ain Shams University, Cairo 11566, EgyptHistology and Cell Biology Department, Faculty of Medicine, Ain Shams University, Cairo 11566, EgyptHistology and Cell Biology Department, Kasralainy Faculty of Medicine, Cairo University, Giza 12613, EgyptGastroenterology and Hepatology Section, Baylor College of Medicine, Houston, TX 77030, USABiochemistry Department, Faculty of Pharmacy, Misr University for Science and Technology, Giza 12566, EgyptMedical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Cairo 11566, EgyptBackground: Non-alcoholic fatty liver disease (NAFLD) represents the most common form of chronic liver disease that urgently needs effective therapy. Rosavin, a major constituent of the Rhodiola Rosea plant of the family Crassulaceae, is believed to exhibit multiple pharmacological effects on diverse diseases. However, its effect on non-alcoholic steatohepatitis (NASH), the progressive form of NAFLD, and the underlying mechanisms are not fully illustrated. Aim: Investigate the pharmacological activity and potential mechanism of rosavin treatment on NASH management via targeting hepatic cell death-related (<i>HSPD1/TNF/MMP14/ITGB1</i>) mRNAs and their upstream noncoding RNA regulators (<i>miRNA-6881-5P</i> and <i>lnc-SPARCL1-1:2</i>) in NASH rats. Results: High sucrose high fat (HSHF) diet-induced NASH rats were treated with different concentrations of rosavin (10, 20, and 30 mg/kg/day) for the last four weeks of dietary manipulation. The data revealed that rosavin had the ability to modulate the expression of the hepatic cell death-related RNA panel through the upregulation of both (<i>HSPD1/TNF/MMP14/ITGB1</i>) mRNAs and their epigenetic regulators (<i>miRNA-6881-5P</i> and <i>lnc-SPARCL1-1:2</i>). Moreover, rosavin ameliorated the deterioration in both liver functions and lipid profile, and thereby improved the hepatic inflammation, fibrosis, and apoptosis, as evidenced by the decreased protein levels of IL6, TNF-α, and caspase-3 in liver sections of treated animals compared to the untreated NASH rats. Conclusion: Rosavin has demonstrated a potential ability to attenuate disease progression and inhibit hepatic cell death in the NASH animal model. The produced effect was correlated with upregulation of the hepatic cell death-related (<i>HSPD1</i>, <i>TNF</i>, <i>MMP14</i>, and <i>ITGB1</i>) mRNAs—(<i>miRNA-6881-5P</i>—(<i>lnc-SPARCL1-1:2</i>) RNA panel.https://www.mdpi.com/1422-0067/23/17/10148rosavinnon-alcoholic steatohepatitishepatic cell deathhepaticinflammationcell detachment |
| spellingShingle | Reda Albadawy Amany Helmy Hasanin Sara H. A. Agwa Shaimaa Hamady Yasmin M. Aboul-Ela Mona Hussien Raafat Samaa Samir Kamar Mohamed Othman Yahia A. Yahia Marwa Matboli Rosavin Ameliorates Hepatic Inflammation and Fibrosis in the NASH Rat Model via Targeting Hepatic Cell Death International Journal of Molecular Sciences rosavin non-alcoholic steatohepatitis hepatic cell death hepatic inflammation cell detachment |
| title | Rosavin Ameliorates Hepatic Inflammation and Fibrosis in the NASH Rat Model via Targeting Hepatic Cell Death |
| title_full | Rosavin Ameliorates Hepatic Inflammation and Fibrosis in the NASH Rat Model via Targeting Hepatic Cell Death |
| title_fullStr | Rosavin Ameliorates Hepatic Inflammation and Fibrosis in the NASH Rat Model via Targeting Hepatic Cell Death |
| title_full_unstemmed | Rosavin Ameliorates Hepatic Inflammation and Fibrosis in the NASH Rat Model via Targeting Hepatic Cell Death |
| title_short | Rosavin Ameliorates Hepatic Inflammation and Fibrosis in the NASH Rat Model via Targeting Hepatic Cell Death |
| title_sort | rosavin ameliorates hepatic inflammation and fibrosis in the nash rat model via targeting hepatic cell death |
| topic | rosavin non-alcoholic steatohepatitis hepatic cell death hepatic inflammation cell detachment |
| url | https://www.mdpi.com/1422-0067/23/17/10148 |
| work_keys_str_mv | AT redaalbadawy rosavinameliorateshepaticinflammationandfibrosisinthenashratmodelviatargetinghepaticcelldeath AT amanyhelmyhasanin rosavinameliorateshepaticinflammationandfibrosisinthenashratmodelviatargetinghepaticcelldeath AT sarahaagwa rosavinameliorateshepaticinflammationandfibrosisinthenashratmodelviatargetinghepaticcelldeath AT shaimaahamady rosavinameliorateshepaticinflammationandfibrosisinthenashratmodelviatargetinghepaticcelldeath AT yasminmaboulela rosavinameliorateshepaticinflammationandfibrosisinthenashratmodelviatargetinghepaticcelldeath AT monahussienraafat rosavinameliorateshepaticinflammationandfibrosisinthenashratmodelviatargetinghepaticcelldeath AT samaasamirkamar rosavinameliorateshepaticinflammationandfibrosisinthenashratmodelviatargetinghepaticcelldeath AT mohamedothman rosavinameliorateshepaticinflammationandfibrosisinthenashratmodelviatargetinghepaticcelldeath AT yahiaayahia rosavinameliorateshepaticinflammationandfibrosisinthenashratmodelviatargetinghepaticcelldeath AT marwamatboli rosavinameliorateshepaticinflammationandfibrosisinthenashratmodelviatargetinghepaticcelldeath |