自身免疫性肝炎（AIH）是一个全球重要的公共卫生问题，目前可供选择的治疗选项很少。《中国药材大辞典》记载了一种主要成分为邓凡朴皂苷的玉米糯米，该药物是一种具有抗炎、抗氧化和抗凋亡特性的中药。然而，迄今为止，玉米糯米对包括AIH在内的自身免疫疾病的影响尚未确定，对玉米糯米在抑制炎症反应方面的作用机制也不清楚。本研究旨在使用小鼠模型研究玉米糯米对AIH的治疗效果。 本研究使用协和豆素（Con A）诱导的AIH小鼠模型评估玉米糯米在抑制体内炎症反应方面的药理活性。将C57BL/6J小鼠静脉注射不同剂量的玉米糯米，3小时后挑战18mg/kg的Con A。进行网络药理学分析，以确定玉米糯米在AIH中的潜在靶基因和信号通路。随后，收集注射Con A 12小时后的血清和肝组织，分析肝损伤、凋亡、氧化应激、免疫反应和炎症标志物的水平。 网络药理学分析揭示，玉米糯米可能通过调节氧化应激和凋亡来调控AIH。与Con A组相比，玉米糯米预处理明显降低了血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶的水平，改善了肝脏的组织病理损伤和凋亡。此外，玉米糯米降低了丙二醛和髓过氧化物酶的水平，升高了超氧化物歧化酶的水平，表明有缓解氧化应激的作用。此外，玉米糯米抑制T细胞和自然杀伤T细胞的活化，而髓源抑制细胞的比例显著增加。促炎细胞因子，包括白介素（IL）-6、IL-12、IL-1β和肿瘤坏死因子-α（TNF-α）的产生也明显减少。最后，Western blot分析显示，玉米糯米抑制了细胞外受体激酶（ERK）和c-Jun N-末端激酶（JNK）的磷酸化。 我们证明了玉米糯米通过ERK和JNK信号通路，抑制氧化应激、凋亡和炎症反应，以及调节免疫细胞的活化和招募，对Con A诱导的免疫介导性肝炎具有保护作用。 版权所有 © 2023 作者。由Elsevier GmbH出版。保留所有权利。

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.The study was aimed to investigate the therapeutic effects of cornuside on AIH using murine models.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.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.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).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.Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.