Garcinone E Mitigates Oxidative Inflammatory Response and Protects against Experimental Autoimmune Hepatitis via Modulation of Nrf2/HO-1, NF-κB and TNF-α/JNK Axis
<i>Garcinia mangostana</i> L. (Clusiaceae), a popular tropical fruit for its juiciness and sweetness, is an opulent fountain of prenylated and oxygenated xanthones with a vast array of bio-activities. Garcinone E (GE), a xanthone derivative reported from <i>G. mangostana,</i>...
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MDPI AG
2022-12-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/15/1/16 |
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| author | Gamal A. Mohamed Sabrin R. M. Ibrahim Rawan H. Hareeri Lenah S. Binmahfouz Amina M. Bagher Hossam M. Abdallah Wael M. Elsaed Dina S. El-Agamy |
| author_facet | Gamal A. Mohamed Sabrin R. M. Ibrahim Rawan H. Hareeri Lenah S. Binmahfouz Amina M. Bagher Hossam M. Abdallah Wael M. Elsaed Dina S. El-Agamy |
| author_sort | Gamal A. Mohamed |
| collection | DOAJ |
| description | <i>Garcinia mangostana</i> L. (Clusiaceae), a popular tropical fruit for its juiciness and sweetness, is an opulent fountain of prenylated and oxygenated xanthones with a vast array of bio-activities. Garcinone E (GE), a xanthone derivative reported from <i>G. mangostana,</i> possesses cytotoxic and aromatase inhibitory activities. The present research endeavors to investigate the hepato-protection efficaciousness of GE on concanavalin-A (Con-A)-instigated hepatitis. Results showed that GE pretreating noticeably diminishes both the serum indices (transaminases, ALP, LDH, and γ-GT) and histopathological lesions of the liver. It counteracted neutrophil and CD4+ infiltration into the liver. GE furthered the Nrf2 genetic expression and its antioxidants’ cascade, which resulted in amelioration of Con-A-caused oxidative stress (OS), lipid per-oxidative markers (4-HNE, MDA, PC) reduction, and intensified antioxidants (TAC, SOD, GSH) in the hepatic tissue. Additionally, GE prohibited NF-ĸB (nuclear factor kappa-B) activation and lessened the genetics and levels of downstream cytokines (IL1β and IL6). Moreover, the TNF-α/JNK axis was repressed in GE-treated mice, which was accompanied by attenuation of Con-A-induced apoptosis. These findings demonstrated the protective potential of GE in Con-A-induced hepatitis which may be associated with Nrf2/HO-1 signaling activation and OS suppression, as well as modulation of the NF-κB and TNF-α/JNK/apoptosis signaling pathway. These results suggest the potential use of GE as a novel hepato-protective agent against autoimmune hepatitis. |
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| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-09T03:29:01Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-fba8c29767664284be951b8ac4435e0a2023-12-03T14:59:08ZengMDPI AGNutrients2072-66432022-12-011511610.3390/nu15010016Garcinone E Mitigates Oxidative Inflammatory Response and Protects against Experimental Autoimmune Hepatitis via Modulation of Nrf2/HO-1, NF-κB and TNF-α/JNK AxisGamal A. Mohamed0Sabrin R. M. Ibrahim1Rawan H. Hareeri2Lenah S. Binmahfouz3Amina M. Bagher4Hossam M. Abdallah5Wael M. Elsaed6Dina S. El-Agamy7Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Chemistry, Preparatory Year Program, Batterjee Medical College, Jeddah 21442, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmacology and Toxicology, 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 Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt<i>Garcinia mangostana</i> L. (Clusiaceae), a popular tropical fruit for its juiciness and sweetness, is an opulent fountain of prenylated and oxygenated xanthones with a vast array of bio-activities. Garcinone E (GE), a xanthone derivative reported from <i>G. mangostana,</i> possesses cytotoxic and aromatase inhibitory activities. The present research endeavors to investigate the hepato-protection efficaciousness of GE on concanavalin-A (Con-A)-instigated hepatitis. Results showed that GE pretreating noticeably diminishes both the serum indices (transaminases, ALP, LDH, and γ-GT) and histopathological lesions of the liver. It counteracted neutrophil and CD4+ infiltration into the liver. GE furthered the Nrf2 genetic expression and its antioxidants’ cascade, which resulted in amelioration of Con-A-caused oxidative stress (OS), lipid per-oxidative markers (4-HNE, MDA, PC) reduction, and intensified antioxidants (TAC, SOD, GSH) in the hepatic tissue. Additionally, GE prohibited NF-ĸB (nuclear factor kappa-B) activation and lessened the genetics and levels of downstream cytokines (IL1β and IL6). Moreover, the TNF-α/JNK axis was repressed in GE-treated mice, which was accompanied by attenuation of Con-A-induced apoptosis. These findings demonstrated the protective potential of GE in Con-A-induced hepatitis which may be associated with Nrf2/HO-1 signaling activation and OS suppression, as well as modulation of the NF-κB and TNF-α/JNK/apoptosis signaling pathway. These results suggest the potential use of GE as a novel hepato-protective agent against autoimmune hepatitis.https://www.mdpi.com/2072-6643/15/1/16<i>Garcinia mangostana</i>Clusiaceaexanthonesgarcinone Ehepatoprotectiveconcanavalin A |
| spellingShingle | Gamal A. Mohamed Sabrin R. M. Ibrahim Rawan H. Hareeri Lenah S. Binmahfouz Amina M. Bagher Hossam M. Abdallah Wael M. Elsaed Dina S. El-Agamy Garcinone E Mitigates Oxidative Inflammatory Response and Protects against Experimental Autoimmune Hepatitis via Modulation of Nrf2/HO-1, NF-κB and TNF-α/JNK Axis Nutrients <i>Garcinia mangostana</i> Clusiaceae xanthones garcinone E hepatoprotective concanavalin A |
| title | Garcinone E Mitigates Oxidative Inflammatory Response and Protects against Experimental Autoimmune Hepatitis via Modulation of Nrf2/HO-1, NF-κB and TNF-α/JNK Axis |
| title_full | Garcinone E Mitigates Oxidative Inflammatory Response and Protects against Experimental Autoimmune Hepatitis via Modulation of Nrf2/HO-1, NF-κB and TNF-α/JNK Axis |
| title_fullStr | Garcinone E Mitigates Oxidative Inflammatory Response and Protects against Experimental Autoimmune Hepatitis via Modulation of Nrf2/HO-1, NF-κB and TNF-α/JNK Axis |
| title_full_unstemmed | Garcinone E Mitigates Oxidative Inflammatory Response and Protects against Experimental Autoimmune Hepatitis via Modulation of Nrf2/HO-1, NF-κB and TNF-α/JNK Axis |
| title_short | Garcinone E Mitigates Oxidative Inflammatory Response and Protects against Experimental Autoimmune Hepatitis via Modulation of Nrf2/HO-1, NF-κB and TNF-α/JNK Axis |
| title_sort | garcinone e mitigates oxidative inflammatory response and protects against experimental autoimmune hepatitis via modulation of nrf2 ho 1 nf κb and tnf α jnk axis |
| topic | <i>Garcinia mangostana</i> Clusiaceae xanthones garcinone E hepatoprotective concanavalin A |
| url | https://www.mdpi.com/2072-6643/15/1/16 |
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