Yanzhan Liu,1,* Yu Wang,2,* Mingchao Jiang,1,* Qilian Zhang,3 Mingtao Yang,1 Fang Sun,1 Zhengguang Xu,1 Tao Liu,4 Jing Yao1,5 

1School of Basic Medicine, Jining Medical University, Jining, 272067, People’s Republic of China; 2Department of Pharmacy, Xuzhou City Hospital of TCM, Xuzhou, 221000, People’s Republic of China; 3Department of Pathology, People’s Hospital Affiliated to Shandong First Medical University, Jinan, 271100, People’s Republic of China; 4Affiliated Hospital of Jining Medical University, Department of Otolaryngology, Head and Neck Surgery, Jining, 272067, People’s Republic of China; 5Jining Key Laboratory of Pharmacology, Jining Medical University, Jining, 272067, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jing Yao, School of Basic Medicine, Jining Medical University, 133 Hehua Road, Jining, 272067, People’s Republic of China, Tel/Fax +863616272, Email yjing_87@163.com

Objective: This study aimed to investigate the protective effects of hordenine on concanavalin A (ConA)-induced immune liver injury (ILI).
Methods: Liver coefficients and spleen coefficients were determined. The serum levels of alanine transaminase (ALT) and aspartate transaminase (AST) were detected. Hematoxylin-eosin (H&E) staining was used to observe the pathological changes of the liver, spleen, and thymus. Immunohistochemical experiments were performed to detect the expression of inflammatory factors interleukin (IL)‐6, IL‐1β, and tumor necrosis factor alpha (TNF‐α) in liver tissues. Superoxide dismutase (SOD) and malondialdehyde (MDA) contents were detected. TdT-Mediated dUTP Nick-End Labeling (TUNEL) staining was used to observe the apoptosis of liver cells. Western Blot was used to detect the expression of B-cell lymphoma-2 (Bcl-2), Caspase-3, Bcl-2-Associated X (Bax), kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2–related factor 2 (Nrf2), and heme oxygenase-1 (HO-1).
Results: We found that hordenine alleviated liver and spleen enlargement, ameliorated pathological damage in the liver, spleen, and thymus, and reduced transaminase and inflammatory factor levels in the liver. Moreover, hordenine increased the level of SOD while decreasing the level of MDA, attenuated hepatic apoptosis, decreased the expression of caspase-3, Bax, and Keap1 and increased the expression of Bcl-2, Nrf2, and HO-1.
Conclusion: These results suggest that hordenine has a protective effect against ConA-induced immune liver injury, which may be related to its modulation of the Keap1/Nrf2/HO-1 pathway and inhibition of oxidative stress and apoptosis.

Keywords: hordenine, immune liver injury, oxidative stress, apoptosis, keap1/Nrf2/HO-1 pathway