Cornuside improves murine autoimmune hepatitis through inhibition of inflammatory responses

  • Phytomedicine. 2023 Nov:120:155077. doi: 10.1016/j.phymed.2023.155077.
Lin Wang  1 ,  Fenglian Yan  2 ,  Junfeng Zhang  2 ,  Yucai Xiao  1 ,  Changying Wang  2 ,  Yuanbo Zhu  2 ,  Chunxia Li  2 ,  Zhihong Liu  2 ,  Wenbo Li  3 ,  Chengduo Wang  3 ,  Jie Liu  3 ,  Hui Zhang  4 ,  Huabao Xiong  5 ,  Dongmei Shi  6
Affiliations
  • 1. Cheeloo College of Medicine, Shandong University, Jinan, China; Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, China.
  • 2. Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, China; Jining Key Laboratory of Immunology, Jining Medical University, Jining, China.
  • 3. Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, China.
  • 4. Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, China; Jining Key Laboratory of Immunology, Jining Medical University, Jining, China. Electronic address: [email protected].
  • 5. Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, China; Jining Key Laboratory of Immunology, Jining Medical University, Jining, China. Electronic address: [email protected].
  • 6. Cheeloo College of Medicine, Shandong University, Jinan, China; Laboratory of Medical Mycology, Department of Dermatology, Jining No.1 People's Hospital, Jining, China. Electronic address: [email protected].
PMID: 37716032 DOI: 10.1016/j.phymed.2023.155077
Abstract

Background: Autoimmune hepatitis (AIH) poses an important public health concern worldwide, with few therapeutic options available. Cornuside, a primary cornel iridoid glycoside present in Cornus officinalis Sieb. et Zucc., is a well-known traditional Chinese medicine that possesses anti-inflammatory, antioxidant and anti-apoptotic properties. However, the effects of cornuside on autoimmune diseases including AIH is still not defined, neither is clear on the mechanisms of cornuside in the suppression of inflammatory responses.

Purpose: The study was aimed to investigate the therapeutic effects of cornuside on AIH using murine models.

Study design: A murine model of AIH induced by concanavalin A (Con A) was used to examine the pharmacological activity of cornuside in suppressing the inflammatory responses in vivo.

Methods: C57BL/6J mice were intravenously with different doses of cornuside and challenged with 18 mg/kg Con A 3 h later. Network pharmacological analysis was performed to identify the potential target genes and signaling pathways by cornuside in AIH. Next serum and liver tissues were collected 12 h after Con A injection to analyze the levels of markers for hepatic injury, Apoptosis, oxidative stress, immune responses, and inflammation.

Results: Network pharmacological analysis revealed that cornuside may modulate oxidative stress and Apoptosis in AIH. Compared with the Con A group, cornuside pretreatment significantly reduced the serum levels of alanine aminotransferase and aspartate aminotransferase, improving histopathological damage and Apoptosis in the livers. In addition, cornuside decreased the levels of malondialdehyde, myeloperoxidase, but increased superoxide dismutase levels, suggesting the relieving of oxidative stress. Furthermore, cornuside suppressed the activation of T and natural killer T cells, whereas the proportion of myeloid-derived suppressor cells was significantly increased. The production of proinflammatory cytokines, including interleukin (IL)-6, IL-12, IL-1β, and tumor necrosis factor-alpha (TNF-α), was also clearly decreased. Finally, western blot analysis displayed that cornuside inhibited the phosphorylation of extracellular receptor kinase (ERK) and c-Jun N-terminal kinase (JNK).

Conclusions: We demonstrated that cornuside has protective effects for Con A-induced immune-mediated hepatitis by suppressing the oxidative stress, Apoptosis, and the inflammatory responses through the ERK and JNK signaling pathways, as well as by modulating the activation and recruitment of immune cells.

Keywords
Autoimmune hepatitis; Concanavalin A; Cornuside; Traditional medicine.
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