Nanfang Hospital, Southern Medical University, Guangzhou 510515, P. R. China.
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, P. R. China.
Am J Chin Med. 2023;51(5):1249-1267. doi: 10.1142/S0192415X2350057X. Epub 2023 Jun 14.
Liver fibrosis is a disease largely driven by resident and recruited macrophages. The phenotypic switch of hepatic macrophages can be achieved by chemo-attractants and cytokines. During a screening of plants traditionally used to treat liver diseases in China, paeoniflorin was identified as a potential drug that affects the polarization of macrophages. The aim of this study was to evaluate the therapeutic effects of paeoniflorin in an animal model of liver fibrosis and explore its underlying mechanisms. Liver fibrosis was induced in Wistar rats via an intraperitoneal injection of CCl. In addition, the RAW264.7 macrophages were cultured in the presence of CoCl to simulate a hypoxic microenvironment of fibrotic livers . The modeled rats were treated daily with either paeoniflorin (100, 150, and 200[Formula: see text]mg/kg) or YC-1 (2[Formula: see text]mg/kg) for 8 weeks. Hepatic function, inflammation and fibrosis, activation of hepatic stellate cells (HSC), and extracellular matrix (ECM) deposition were assessed in the and models. The expression levels of M1 and M2 macrophage markers and the NF-[Formula: see text]B/HIF-1[Formula: see text] pathway factors were measured using standard assays. Paeoniflorin significantly alleviated hepatic inflammation and fibrosis, as well as hepatocyte necrosis in the CCl-induced fibrosis model. Furthermore, paeoniflorin also inhibited HSC activation and reduced ECM deposition both and . Mechanistically, paeoniflorin restrained M1 macrophage polarization and induced M2 polarization in the fibrotic liver tissues as well as in the RAW264.7 cells grown under hypoxic conditions by inactivating the NF-[Formula: see text]B/HIF-1[Formula: see text] signaling pathway. In conclusion, paeoniflorin exerts its anti-inflammatory and anti-fibrotic effects in the liver by coordinating macrophage polarization through the NF-[Formula: see text]B/HIF-1[Formula: see text] pathway.
肝纤维化主要由固有巨噬细胞和募集的巨噬细胞驱动。肝巨噬细胞的表型转换可以通过趋化因子和细胞因子来实现。在筛选中国传统用于治疗肝脏疾病的植物时，鉴定出芍药苷是一种影响巨噬细胞极化的潜在药物。本研究旨在评估芍药苷在肝纤维化动物模型中的治疗效果，并探讨其潜在机制。通过腹腔注射 CCl 诱导 Wistar 大鼠肝纤维化，此外，RAW264.7 巨噬细胞在 CoCl 存在的情况下培养，模拟纤维化肝脏的低氧微环境。建模大鼠每天用芍药苷（100、150 和 200[Formula: see text]mg/kg）或 YC-1（2[Formula: see text]mg/kg）治疗 8 周。在[Formula: see text]和[Formula: see text]模型中评估肝功能、炎症和纤维化、肝星状细胞（HSC）激活和细胞外基质（ECM）沉积。使用标准测定法测量 M1 和 M2 巨噬细胞标志物和 NF-[Formula: see text]B/HIF-1[Formula: see text]途径因子的表达水平。芍药苷显著减轻 CCl 诱导的纤维化模型中的肝炎症和纤维化以及肝细胞坏死。此外，芍药苷还抑制 HSC 激活并减少 ECM 沉积[Formula: see text]和[Formula: see text]。在机制上，芍药苷通过抑制 NF-[Formula: see text]B/HIF-1[Formula: see text]信号通路，在纤维化肝组织以及在低氧条件下生长的 RAW264.7 细胞中抑制 M1 巨噬细胞极化并诱导 M2 极化。总之，芍药苷通过 NF-[Formula: see text]B/HIF-1[Formula: see text]途径协调巨噬细胞极化，在肝脏中发挥抗炎和抗纤维化作用。
