Abstract

ORIDONIN EFFECT ON AUTO IMMUNE HEPATITIS INDUCED IN MICE

Saif Dhahir, Fatma M. Amin, Manar A. Nader*

ABSTRACT

Background: Oridonin (ORI), a bioactive diterpenoid, exhibits potent anti-inflammatory, antioxidant, and immunoregulatory activities. Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disease characterized by lymphocyte-driven hepatic inflammation, excessive cytokine production, and progressive liver injury. Given the pharmacological properties of ORI and the need for safe hepatoprotective agents; ORI was anticipated as a potential hepatoprotective agent against AIH. Objective: This study was designed to evaluate the protective effects of ORI in a concanavalin A (Con-A)-induced mouse model of AIH, targeting AKT/PI3K/mTOR–NLRP3 inflammatory signaling, oxidative stress, and M1/M2 polarization. Methods: Thirty male BALB/c mice were divided into three groups, CTR group, Con-A group, ORI (5 mg/kg) + Con-A group. ORI was administered i.p for 4 days before a single Con-A injection (15 mg/kg i.v.). Liver injury was examined on the basis of serum liver enzymes, examination of oxidative stress and pro-inflammatory markers. Results: ORI pretreatment mitigated Con-A-induced hepatocellular injury, oxidative stress, and. It significantly reduced liver enzyme elevation, suppressed oxidative stress. Furthermore, ORI downregulated IL-6 as pro-inflammatory markers. Conclusion: ORI exhibits hepatoprotective potential against Con-A-induced AIH by reducing oxidative stress and inflammation.

Keywords: ORI, AIH, Con-A model, SOD, IL-6.