SIRT1/Nrf2/NF-κB Signaling Mediates Anti-Inflammatory and Anti-Apoptotic Activities of Oleanolic Acid in a Mouse Model of Acute Hepatorenal Damage
<i>Background and objectives:</i> Oleanolic acid (OA) is a penta-cyclic triterpene with diverse bioactivities such as anticarcinogenic, antiviral, antimicrobial, hepatoprotective, anti-atherosclerotic, hypolipidemic, and gastroprotective. However, its effects on hepatorenal damage remain...
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MDPI AG
2023-07-01
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| Online Access: | https://www.mdpi.com/1648-9144/59/7/1351 |
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| author | Manea A. I. Alqrad Dina S. El-Agamy Sabrin R. M. Ibrahim Alaa Sirwi Hossam M. Abdallah Essam Abdel-Sattar Ali M. El-Halawany Wael M. Elsaed Gamal A. Mohamed |
| author_facet | Manea A. I. Alqrad Dina S. El-Agamy Sabrin R. M. Ibrahim Alaa Sirwi Hossam M. Abdallah Essam Abdel-Sattar Ali M. El-Halawany Wael M. Elsaed Gamal A. Mohamed |
| author_sort | Manea A. I. Alqrad |
| collection | DOAJ |
| description | <i>Background and objectives:</i> Oleanolic acid (OA) is a penta-cyclic triterpene with diverse bioactivities such as anticarcinogenic, antiviral, antimicrobial, hepatoprotective, anti-atherosclerotic, hypolipidemic, and gastroprotective. However, its effects on hepatorenal damage remain unclear. The protective activity of OA, separated from <i>Viscum schimperi</i> (Loranthaceae), against TAA (thioacetamide)-produced acute hepatic and renal damage was explored. <i>Materials and Methods:</i> Mice were treated with OA for 7 days before TAA (200 mg/kg, i.p.). Serum indices of hepatorenal injury, pathological lesions, molecular biological indexes, and inflammatory/apoptotic genes were estimated. <i>Results:</i> The tissues of both organs were greatly affected by the TAA injection. That was evident through increased serum markers of hepato-renal injury as well as remarkable histopathological lesions. TAA-induced injury was associated with oxidative and inflammatory responses in both organs as there was an elevation of oxidative stress parameters (4-HNE (4-hydroxy-nonenal), MDA (malondialdehyde), NOx (nitric oxide)), decline of antioxidants (reduced glutathione (GSH), superoxide dismutase (SOD), and total antioxidant capacity (TAC)), and an increase in the gene expression/level of inflammatory mediators (interleukins (1β&6)). The inflammatory response was linked to a significant activation of NF-κB (nuclear-factor kappa-B)/TNF-α (tumor-necrosis factor-alpha) signaling. The inflammatory response in both organs was accompanied by apoptotic changes, including a rise in the gene expression and level of apoptotic parameters (caspase-3 and Bax) along with a decline in Bcl-2 (anti-apoptotic parameter) gene expression and level. These pathogenic events were found to be closely related to the suppression of the antioxidant signaling pathway, Nrf2 (nuclear-factor erythroid 2–related factor-2)/SIRT1 (sirtuin-1)/HO-1 (heme-oxygenase 1). On the other hand, OA significantly ameliorated TAA-induced injury in both organs. On the other hand, OA counterpoised the inflammatory response as it ameliorated NF-κB/TNF-α signaling and cytokine release. OA enhanced Nrf2/SIRT1/HO-1 signaling and counteracted apoptotic damage. <i>Conclusions:</i> OA showed anti-inflammation and antiapoptotic capacities that effectively suppressed TAA-induced acute hepatorenal damage. |
| first_indexed | 2024-03-11T00:50:54Z |
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| last_indexed | 2024-03-11T00:50:54Z |
| publishDate | 2023-07-01 |
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| spelling | doaj.art-78976ac7959042149450950faf2883e82023-11-18T20:25:36ZengMDPI AGMedicina1010-660X1648-91442023-07-01597135110.3390/medicina59071351SIRT1/Nrf2/NF-κB Signaling Mediates Anti-Inflammatory and Anti-Apoptotic Activities of Oleanolic Acid in a Mouse Model of Acute Hepatorenal DamageManea A. I. Alqrad0Dina S. El-Agamy1Sabrin R. M. Ibrahim2Alaa Sirwi3Hossam M. Abdallah4Essam Abdel-Sattar5Ali M. El-Halawany6Wael M. Elsaed7Gamal A. Mohamed8Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, EgyptDepartment of Chemistry, Preparatory Year Program, Batterjee Medical College, Jeddah 21442, Saudi ArabiaDepartment of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmacognosy, Faculty of Pharmacy, Cairo University, Giza 12613, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Cairo University, Giza 12613, EgyptDepartment of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, EgyptDepartment of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia<i>Background and objectives:</i> Oleanolic acid (OA) is a penta-cyclic triterpene with diverse bioactivities such as anticarcinogenic, antiviral, antimicrobial, hepatoprotective, anti-atherosclerotic, hypolipidemic, and gastroprotective. However, its effects on hepatorenal damage remain unclear. The protective activity of OA, separated from <i>Viscum schimperi</i> (Loranthaceae), against TAA (thioacetamide)-produced acute hepatic and renal damage was explored. <i>Materials and Methods:</i> Mice were treated with OA for 7 days before TAA (200 mg/kg, i.p.). Serum indices of hepatorenal injury, pathological lesions, molecular biological indexes, and inflammatory/apoptotic genes were estimated. <i>Results:</i> The tissues of both organs were greatly affected by the TAA injection. That was evident through increased serum markers of hepato-renal injury as well as remarkable histopathological lesions. TAA-induced injury was associated with oxidative and inflammatory responses in both organs as there was an elevation of oxidative stress parameters (4-HNE (4-hydroxy-nonenal), MDA (malondialdehyde), NOx (nitric oxide)), decline of antioxidants (reduced glutathione (GSH), superoxide dismutase (SOD), and total antioxidant capacity (TAC)), and an increase in the gene expression/level of inflammatory mediators (interleukins (1β&6)). The inflammatory response was linked to a significant activation of NF-κB (nuclear-factor kappa-B)/TNF-α (tumor-necrosis factor-alpha) signaling. The inflammatory response in both organs was accompanied by apoptotic changes, including a rise in the gene expression and level of apoptotic parameters (caspase-3 and Bax) along with a decline in Bcl-2 (anti-apoptotic parameter) gene expression and level. These pathogenic events were found to be closely related to the suppression of the antioxidant signaling pathway, Nrf2 (nuclear-factor erythroid 2–related factor-2)/SIRT1 (sirtuin-1)/HO-1 (heme-oxygenase 1). On the other hand, OA significantly ameliorated TAA-induced injury in both organs. On the other hand, OA counterpoised the inflammatory response as it ameliorated NF-κB/TNF-α signaling and cytokine release. OA enhanced Nrf2/SIRT1/HO-1 signaling and counteracted apoptotic damage. <i>Conclusions:</i> OA showed anti-inflammation and antiapoptotic capacities that effectively suppressed TAA-induced acute hepatorenal damage.https://www.mdpi.com/1648-9144/59/7/1351oleanolic acid<i>Viscum schimperi</i>thioacetamideSIRT1/Nrf2/NF-κBhepatorenal damageBax/Bcl-2 |
| spellingShingle | Manea A. I. Alqrad Dina S. El-Agamy Sabrin R. M. Ibrahim Alaa Sirwi Hossam M. Abdallah Essam Abdel-Sattar Ali M. El-Halawany Wael M. Elsaed Gamal A. Mohamed SIRT1/Nrf2/NF-κB Signaling Mediates Anti-Inflammatory and Anti-Apoptotic Activities of Oleanolic Acid in a Mouse Model of Acute Hepatorenal Damage Medicina oleanolic acid <i>Viscum schimperi</i> thioacetamide SIRT1/Nrf2/NF-κB hepatorenal damage Bax/Bcl-2 |
| title | SIRT1/Nrf2/NF-κB Signaling Mediates Anti-Inflammatory and Anti-Apoptotic Activities of Oleanolic Acid in a Mouse Model of Acute Hepatorenal Damage |
| title_full | SIRT1/Nrf2/NF-κB Signaling Mediates Anti-Inflammatory and Anti-Apoptotic Activities of Oleanolic Acid in a Mouse Model of Acute Hepatorenal Damage |
| title_fullStr | SIRT1/Nrf2/NF-κB Signaling Mediates Anti-Inflammatory and Anti-Apoptotic Activities of Oleanolic Acid in a Mouse Model of Acute Hepatorenal Damage |
| title_full_unstemmed | SIRT1/Nrf2/NF-κB Signaling Mediates Anti-Inflammatory and Anti-Apoptotic Activities of Oleanolic Acid in a Mouse Model of Acute Hepatorenal Damage |
| title_short | SIRT1/Nrf2/NF-κB Signaling Mediates Anti-Inflammatory and Anti-Apoptotic Activities of Oleanolic Acid in a Mouse Model of Acute Hepatorenal Damage |
| title_sort | sirt1 nrf2 nf κb signaling mediates anti inflammatory and anti apoptotic activities of oleanolic acid in a mouse model of acute hepatorenal damage |
| topic | oleanolic acid <i>Viscum schimperi</i> thioacetamide SIRT1/Nrf2/NF-κB hepatorenal damage Bax/Bcl-2 |
| url | https://www.mdpi.com/1648-9144/59/7/1351 |
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