Possible Implication of Nrf2, PPAR-γ and MAPKs Signaling in the Protective Role of Mangiferin against Renal Ischemia/Reperfusion in Rats
Mangiferin (Mang) is a known glucosylxanthone that has proven its shielding effect against ischemia/reperfusion (Is/R). However, its full underlying mechanistic perspective against renal Is/R induced lesions is not fully revealed. Consequently, the purpose of this study is to track further non-inves...
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MDPI AG
2022-12-01
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| author | Abdallah M. Gendy Amira A. El-Gazar Ghada M. Ragab Asmaa K. Al-Mokaddem Alaadin E. El-Haddad Heba Mohammed Refat M. Selim Einas Mohamed Yousef Najat O. Hamed Sherihan Salaheldin Abdelhamid Ibrahim |
| author_facet | Abdallah M. Gendy Amira A. El-Gazar Ghada M. Ragab Asmaa K. Al-Mokaddem Alaadin E. El-Haddad Heba Mohammed Refat M. Selim Einas Mohamed Yousef Najat O. Hamed Sherihan Salaheldin Abdelhamid Ibrahim |
| author_sort | Abdallah M. Gendy |
| collection | DOAJ |
| description | Mangiferin (Mang) is a known glucosylxanthone that has proven its shielding effect against ischemia/reperfusion (Is/R). However, its full underlying mechanistic perspective against renal Is/R induced lesions is not fully revealed. Consequently, the purpose of this study is to track further non-investigated modulatory signals of Mang against the renal Is/R model involving nuclear factor erythroid 2-related factor (Nrf)2/heme oxygenase (HO)-1, peroxisome proliferator-activated receptor (PPAR)-γ/nuclear factor (NF)-κB, p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) signaling. To ratify our aim, Mang was administrated (20 mg/kg, i.p for seven days) before the induction of bilateral Is/R. Mechanistic maneuver revealed that Mang balanced oxidative state via increasing the expression of the antioxidant Nrf2/HO-1 cue with subsequent enhancement of GSH besides MDA lessening. Additionally, Mang enhanced PPAR-γ mRNA expression and declined <i>p</i>-p38 MAPK and <i>p</i>-JNK expression with concomitant NF-κB downsizing leading to iNOS/NOx and TNF-α rebating. Furthermore, the Mang anti-apoptotic trait was affirmed by enriching Bcl-2 expression as well as decreasing Bax and caspase-3 expression. All these potentials were in the line with the molecular docking results and the improved histopathological findings and renal function biomarkers. Consequently, Mang provided plausible protective mechanisms against renal Is/R-related events, possibly by amending oxidative status, inflammatory mediators, and apoptotic cell death through the involvement of Nrf2, PPAR-γ, MAPK, JNK, and NF-κB signaling. |
| first_indexed | 2024-03-09T11:29:47Z |
| format | Article |
| id | doaj.art-aebb96e7054d4fe6b64502df13645552 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T11:29:47Z |
| publishDate | 2022-12-01 |
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| series | Pharmaceuticals |
| spelling | doaj.art-aebb96e7054d4fe6b64502df136455522023-11-30T23:54:26ZengMDPI AGPharmaceuticals1424-82472022-12-01161610.3390/ph16010006Possible Implication of Nrf2, PPAR-γ and MAPKs Signaling in the Protective Role of Mangiferin against Renal Ischemia/Reperfusion in RatsAbdallah M. Gendy0Amira A. El-Gazar1Ghada M. Ragab2Asmaa K. Al-Mokaddem3Alaadin E. El-Haddad4Heba Mohammed Refat M. Selim5Einas Mohamed Yousef6Najat O. Hamed7Sherihan Salaheldin Abdelhamid Ibrahim8Pharmacology and Toxicology Department, Faculty of Pharmacy, October 6 University, Giza 12585, EgyptPharmacology and Toxicology Department, Faculty of Pharmacy, October 6 University, Giza 12585, EgyptPharmacology and Toxicology Department, Faculty of Pharmacy, Misr University for Science and Technology, Giza 12585, EgyptPathology Department, Faculty of Veterinary Medicine, Cairo University, Giza 12211, EgyptPharmacognosy Department, Faculty of Pharmacy, October 6 University, Giza 12585, EgyptPharmaceutical Sciences Department, Faculty of Pharmacy, Al-Maarefa University, Diriyah, Riyadh 13713, Saudi ArabiaHistology and Cell biology Department, Faculty of Medicine, Menoufia University, Menoufia 11411, EgyptPharmaceutical Sciences Department, Faculty of Pharmacy, Al-Maarefa University, Diriyah, Riyadh 13713, Saudi ArabiaPharmacology and Therapeutics Department, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria 21523, EgyptMangiferin (Mang) is a known glucosylxanthone that has proven its shielding effect against ischemia/reperfusion (Is/R). However, its full underlying mechanistic perspective against renal Is/R induced lesions is not fully revealed. Consequently, the purpose of this study is to track further non-investigated modulatory signals of Mang against the renal Is/R model involving nuclear factor erythroid 2-related factor (Nrf)2/heme oxygenase (HO)-1, peroxisome proliferator-activated receptor (PPAR)-γ/nuclear factor (NF)-κB, p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) signaling. To ratify our aim, Mang was administrated (20 mg/kg, i.p for seven days) before the induction of bilateral Is/R. Mechanistic maneuver revealed that Mang balanced oxidative state via increasing the expression of the antioxidant Nrf2/HO-1 cue with subsequent enhancement of GSH besides MDA lessening. Additionally, Mang enhanced PPAR-γ mRNA expression and declined <i>p</i>-p38 MAPK and <i>p</i>-JNK expression with concomitant NF-κB downsizing leading to iNOS/NOx and TNF-α rebating. Furthermore, the Mang anti-apoptotic trait was affirmed by enriching Bcl-2 expression as well as decreasing Bax and caspase-3 expression. All these potentials were in the line with the molecular docking results and the improved histopathological findings and renal function biomarkers. Consequently, Mang provided plausible protective mechanisms against renal Is/R-related events, possibly by amending oxidative status, inflammatory mediators, and apoptotic cell death through the involvement of Nrf2, PPAR-γ, MAPK, JNK, and NF-κB signaling.https://www.mdpi.com/1424-8247/16/1/6mangiferinrenal ischemiaNrf2/HO-1PPAR-γ/NF-κBMAPK/JNK |
| spellingShingle | Abdallah M. Gendy Amira A. El-Gazar Ghada M. Ragab Asmaa K. Al-Mokaddem Alaadin E. El-Haddad Heba Mohammed Refat M. Selim Einas Mohamed Yousef Najat O. Hamed Sherihan Salaheldin Abdelhamid Ibrahim Possible Implication of Nrf2, PPAR-γ and MAPKs Signaling in the Protective Role of Mangiferin against Renal Ischemia/Reperfusion in Rats Pharmaceuticals mangiferin renal ischemia Nrf2/HO-1 PPAR-γ/NF-κB MAPK/JNK |
| title | Possible Implication of Nrf2, PPAR-γ and MAPKs Signaling in the Protective Role of Mangiferin against Renal Ischemia/Reperfusion in Rats |
| title_full | Possible Implication of Nrf2, PPAR-γ and MAPKs Signaling in the Protective Role of Mangiferin against Renal Ischemia/Reperfusion in Rats |
| title_fullStr | Possible Implication of Nrf2, PPAR-γ and MAPKs Signaling in the Protective Role of Mangiferin against Renal Ischemia/Reperfusion in Rats |
| title_full_unstemmed | Possible Implication of Nrf2, PPAR-γ and MAPKs Signaling in the Protective Role of Mangiferin against Renal Ischemia/Reperfusion in Rats |
| title_short | Possible Implication of Nrf2, PPAR-γ and MAPKs Signaling in the Protective Role of Mangiferin against Renal Ischemia/Reperfusion in Rats |
| title_sort | possible implication of nrf2 ppar γ and mapks signaling in the protective role of mangiferin against renal ischemia reperfusion in rats |
| topic | mangiferin renal ischemia Nrf2/HO-1 PPAR-γ/NF-κB MAPK/JNK |
| url | https://www.mdpi.com/1424-8247/16/1/6 |
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