Naringin as a natural candidate for anti-autoimmune hepatitis: Inhibitory potency and hepatoprotective mechanism

Qiaozhen Zhu; Yizhuo Jiang; Wenyuan Lin; Mengju Gao; Xiaoyang Chen; Xinyu Li; Haofei Wang; Xinli Niu; Junpeng Wang

doi:10.1016/j.phymed.2024.155722

Naringin as a natural candidate for anti-autoimmune hepatitis: Inhibitory potency and hepatoprotective mechanism

Phytomedicine. 2024 May 6:129:155722. doi: 10.1016/j.phymed.2024.155722. Online ahead of print.

Authors

Qiaozhen Zhu¹, Yizhuo Jiang¹, Wenyuan Lin¹, Mengju Gao¹, Xiaoyang Chen², Xinyu Li¹, Haofei Wang³, Xinli Niu⁴, Junpeng Wang⁵

Affiliations

¹ Infection and Immunity Institute and Translational Medical Center of Huaihe Hospital, Henan University, Kaifeng 475000, PR China.
² School of Chemical and Environmental Engineering, Shanghai Institute Of Technology, Shanghai 050092, PR China.
³ College of Information Engineering (College of Software), Henan University of Animal Husbandry and Economy, Zhengzhou 450044, PR China.
⁴ School of Life Science, Henan University, Kaifeng, 475000, PR China.
⁵ Infection and Immunity Institute and Translational Medical Center of Huaihe Hospital, Henan University, Kaifeng 475000, PR China. Electronic address: jpwangchina@henu.edu.cn.

PMID: 38733905
DOI: 10.1016/j.phymed.2024.155722

Abstract

Background: Autoimmune hepatitis (AIH), primarily mediated by T cells, is characterized by liver inflammation. Despite the advancements in understanding its pathogenesis, effective therapeutic options are limited. Naringin, a flavonoid abundant in citrus fruits, is recognized for its anti-inflammatory properties and ability to protect against various inflammatory diseases, including drug-induced liver injury. However, the exact effects of naringin on AIH and the mechanisms involved remain poorly understood.

Purpose: We aim to determine the role of naringin in AIH, exploring its targets and actions in this disease.

Methods: Network pharmacology, molecular docking, and molecular dynamics simulations were utilized to predict the HUB targets connecting naringin, T cell-mediated autoimmune disorders, and AIH. Cellular thermal shift assays were used to determine the binding abilities of naringin with the HUB targets. An in vivo experiment confirmed the impact of naringin treatment on AIH development and underlying mechanisms.

Results: Naringin demonstrated therapeutic effects on ConA-induced AIH. There were 455 shared targets between naringin, T cell-mediated autoimmune diseases, and AIH. Ten HUB genes (AKT1, ALB, IL-6, IL-1β, CTNNB1, TNF, TP53, MAPK3, VEGFA, and JUN) were identified through the PPI network. Gene ontology analysis revealed involvement in gene expression regulation, lipopolysaccharide-mediated signaling, and I-kappa kinase/NFκB signaling. Pathway analysis suggested TNF, Th1/Th2 cell differentiation, and Toll-like receptor pathways, with favorable naringin-HUB gene binding. Molecular docking confirmed albumin (ALB), IL-1β, IL-6, and TNF as primary targets for naringin. Molecular dynamics simulations showed stable binding in ALB-naringin, TNF-naringin, and IL-1β-naringin complexes. Naringin's hepatoprotective effect on AIH was supported by increased serum ALB and decreased hepatic inflammatory cytokines including IL-1β, IL-6, and TNF-α.

Conclusion: Our data underscore the potential of naringin as a preventive or therapeutical agent in T cell-mediated autoimmune diseases including AIH.

Keywords: Autoimmune hepatitis; Molecular docking; Molecular dynamic simulation; Naringin; T cell-mediated autoimmune diseases.