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. 2022 Dec 21;15(1):16. doi: 10.3390/nu15010016.

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.

Keywords: Clusiaceae; Garcinia mangostana; concanavalin A; garcinone E; hepatitis; hepatoprotective; industrial development; xanthones.

MeSH terms

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

Substances

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