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.

Abstract

Garcinia mangostana 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 G. mangostana, 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.

• Authors: 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
• Journal: Nutrients (Nutrients) Vol. 15 Issue 1 (Dec 21 2022) ISSN: 2072-6643 [Electronic] Switzerland
• PMID: 36615674 (Publication Type: Journal Article)

Chemical References

• NF-kappa B
• Antioxidants
• Tumor Necrosis Factor-alpha
• garcinone E
• NF-E2-Related Factor 2
• Aromatase Inhibitors

Topics

• Animals
• Mice
• NF-kappa B (metabolism)
• Hepatitis, Autoimmune (prevention & control)
• Antioxidants (pharmacology, metabolism)
• Tumor Necrosis Factor-alpha (metabolism)
• NF-E2-Related Factor 2 (genetics, metabolism)
• Aromatase Inhibitors
• Liver (metabolism)
• Oxidative Stress