Li Nan, Wu Jing-Jing, Qi Meng, Wang Zi-Ying, Zhang Sheng-Nan, Li Xiu-Qin, Chen Ting-Ting, Wang Mei-Fang, Zhang Ling-Ling, Wei Wei, Sun Wu-Yi
Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei, China.
Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
Front Pharmacol. 2022 Nov 15;13:1041671. doi: 10.3389/fphar.2022.1041671. eCollection 2022.
Hepatitis is a complex multifactorial pathological disorder, which can eventually lead to liver failure and even potentially be life threatening. Paeoniflorin-6'-O-benzene sulfonate (CP-25) has proven to have critical anti-inflammatory effects in arthritis. However, the effects of CP-25 in the pathogenesis of hepatitis remains unclear. In this experiment, mice were intragastrically administered with CP-25 (25, 50 and 100 mg/kg), and then ConA (25 mg/kg) was intravenous injected to establish hepatitis model . CP-25 administration attenuated liver damage and decreased ALT and AST activities in mice with hepatitis. Besides, CP-25 modulated immune responses including down-regulated the proportions of activated CD4, activated CD8 T cells, and ratio of Th1/Th2 in ConA-injected mice. Furthermore, ConA-mediated production of reactive oxygen species (ROS), release of inflammatory cytokines including IFN-γ, TNF-α, activation of MAPK pathways and nuclear translocation of nuclear factor-kappaB (NF-κB) were significantly decreased in CP-25 administrated mice. In ConA-stimulated RAW264.7 cells, CP-25 suppressed inflammatory cytokines secretion and reduced ROS level, which were consistent with animal experiments. Otherwise, the data showed that CP-25 restrained phosphorylation of ERK, JNK and p38 MAPK pathways influenced by ROS, accompanied with inhibiting NF-κB nuclear translocation. In conclusion, our findings indicated that CP-25 protected against ConA-induced hepatitis may through modulating immune responses and attenuating ROS-mediated inflammation via the MAPK/NF-κB signaling pathway.
肝炎是一种复杂的多因素病理紊乱疾病，最终可导致肝衰竭，甚至有潜在的生命危险。芍药苷-6'-O-苯磺酸盐（CP-25）已被证明在关节炎中具有关键的抗炎作用。然而，CP-25在肝炎发病机制中的作用仍不清楚。在本实验中，给小鼠灌胃CP-25（25、50和100mg/kg），然后静脉注射刀豆蛋白A（ConA，25mg/kg）以建立肝炎模型。给予CP-25可减轻肝炎小鼠的肝损伤，并降低其谷丙转氨酶（ALT）和谷草转氨酶（AST）活性。此外，CP-25调节免疫反应，包括下调注射ConA小鼠体内活化CD4、活化CD8 T细胞的比例以及Th1/Th2比值。此外，在给予CP-25的小鼠中，ConA介导的活性氧（ROS）产生、包括干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）在内的炎性细胞因子释放、丝裂原活化蛋白激酶（MAPK）通路的激活以及核因子-κB（NF-κB）的核转位均显著降低。在ConA刺激的RAW264.7细胞中，CP-25抑制炎性细胞因子分泌并降低ROS水平，这与动物实验结果一致。此外，数据显示CP-25抑制了受ROS影响的细胞外信号调节激酶（ERK）、c-Jun氨基末端激酶（JNK）和p38 MAPK通路的磷酸化，同时抑制NF-κB核转位。总之，我们的研究结果表明，CP-25对ConA诱导的肝炎具有保护作用，可能是通过调节免疫反应并经由MAPK/NF-κB信号通路减轻ROS介导的炎症实现的。
