The First Clinical Medical College, Nanjing University of Traditional Chinese Medicine, Nanjing, China; Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China.
Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China.
J Ethnopharmacol. 2019 Jun 28;238:111861. doi: 10.1016/j.jep.2019.111861. Epub 2019 Apr 4.
Wang-bi tablet (WB) consists of 17 traditional Chinese medicines and has been used for treating rheumatoid arthritis (RA) in China for many years, however, its pharmacologic mechanism is not clear.
The aim of this study was to investigate the therapeutic effect of WB on collagen-induced mouse arthritis and explored the underlying mechanism.
DBA/1 mice were used to establish a type II collagen-induced arthritis (CIA) model. From the day of arthritis onset, mice were treated daily by gavage with either total glucosides of paeony (TGP, 0.37 g/kg/d) or WB at a lower (1.11 g/kg/d, WBL) or higher dose of (3.33 g/kg/d, WBH) for 8 weeks. The severity of arthritis, levels of cytokines and the activation of signaling pathways were determined.
Our results revealed that WB treatment effectively alleviated inflammatory symptoms and prevented bone erosions and joint destructions. It obviously decreased the serum concentration of pro-inflammatory cytokines TNF-α, IL-6 and IL-17α, while increased the concentration of anti-inflammatory cytokine IL-10. Interestingly, the proportion of splenic Treg cells were increased significantly. In vitro experiments showed that WB inhibited the differentiation of osteoclasts. Consistently, the mRNA levels of tartrate-resistant acid phosphatase (TRAP) and cathepsin K (CtsK), and the activation of NF-κB and JAK-STAT3 signaling pathways in the paws of CIA mice were inhibited by WB treatment. On the other hand, up-regulation of osteogenic genes Runx2, Osterix mRNA, and activation of Wnt/β-catenin signaling pathway along with a decreased receptor activator of nuclear factor κB ligand (RANKL) expression were found in WB treated mice.
Our results suggest that the therapeutic effect of Wang-bi tablet could be attributed to its inhibitory activity on NF-κB and STAT3 signaling pathway-mediated osteoclast differentiation, and its enhancement on Wnt/β-catenin signaling pathway-mediated osteoblast functions.
王痹片（WB）由 17 种中药组成，多年来一直用于治疗类风湿关节炎（RA），但其药理机制尚不清楚。
本研究旨在探讨 WB 对胶原诱导的小鼠关节炎的治疗作用，并探讨其潜在机制。
采用 DBA/1 小鼠建立 II 型胶原诱导性关节炎（CIA）模型。从关节炎发病的第一天开始，通过灌胃每天给予白芍总苷（TGP，0.37 g/kg/d）或 WB 的低（1.11 g/kg/d，WBL）或高剂量（3.33 g/kg/d，WBH），连续 8 周。测定关节炎的严重程度、细胞因子水平及信号通路的激活情况。
结果表明，WB 治疗能有效缓解炎症症状，防止骨侵蚀和关节破坏。它明显降低了血清中促炎细胞因子 TNF-α、IL-6 和 IL-17α 的浓度，同时增加了抗炎细胞因子 IL-10 的浓度。有趣的是，脾 Treg 细胞的比例明显增加。体外实验表明 WB 抑制破骨细胞的分化。同样，WB 治疗抑制 CIA 小鼠爪子中抗酒石酸酸性磷酸酶（TRAP）和组织蛋白酶 K（CtsK）的 mRNA 水平以及 NF-κB 和 JAK-STAT3 信号通路的激活。另一方面，在 WB 处理的小鼠中发现成骨基因 Runx2、Osterix mRNA 的上调以及 Wnt/β-catenin 信号通路的激活，同时降低核因子κB 受体激活剂配体（RANKL）的表达。
研究结果表明，王痹片的治疗效果可能归因于其对 NF-κB 和 STAT3 信号通路介导的破骨细胞分化的抑制作用，以及对 Wnt/β-catenin 信号通路介导的成骨细胞功能的增强。
