School of Pharmacy, Key Laboratory for Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, Anhui, China , Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Hefei 230032, China , The Anhui Mental Health Center, Hefei 230022, China.
Am J Chin Med. 2014;42(4):905-19. doi: 10.1142/S0192415X14500578.
Macrophages play a crucial role in rheumatoid arthritis (RA). Their activation is the initial step of RA. This study was designed to detect the effects of total flavonoids from Litsea coreana Levl. (TFLC) on the complete Freund's adjuvant-induced (CFA-induced) arthritis (AA) in rats and to explore whether inflammatory cytokines were induced by the IRE1/mTORC1/TNF-α-dependant mechanism in peritoneal macrophages. In vivo, our data indicated that TFLC (100, 200 mg/kg, i.g. × 10 days) could significantly suppress secondary paw swelling and serum levels of TNF-α and IL-1β. Histopathological figures showed that TFLC treatment improved the morphologic changes of articular cartilages and synovium. Results of RT-PCR and western blotting demonstrated that TFLC suppressed expression of 78-KD glucose regulated protein (GRP78), X-box binding protein 1 (XBP1), mTOR complex 1 (mTORC1) and TNF-α in peritoneal macrophages of AA rats. Collectively, these results indicate that TFLC is able to ameliorate adjuvant-induced arthritis in a dose-dependent manner by suppressing the IRE1/mTORC1/TNF-α-regulated inflammatory response initiated in peritoneal macrophages.
巨噬细胞在类风湿关节炎（RA）中发挥着至关重要的作用。它们的激活是 RA 的初始步骤。本研究旨在检测山鸡椒总黄酮（TFLC）对完全弗氏佐剂诱导的关节炎（AA）大鼠的影响，并探讨其是否通过 IRE1/mTORC1/TNF-α依赖机制诱导腹腔巨噬细胞中的炎症细胞因子。在体内，我们的数据表明，TFLC（100、200mg/kg，ig.×10 天）可显著抑制继发性爪肿胀和血清中 TNF-α和 IL-1β的水平。组织病理学图片表明，TFLC 治疗可改善关节软骨和滑膜的形态变化。RT-PCR 和 Western blot 结果表明，TFLC 抑制了 AA 大鼠腹腔巨噬细胞中 78-KD 葡萄糖调节蛋白（GRP78）、X 盒结合蛋白 1（XBP1）、mTOR 复合物 1（mTORC1）和 TNF-α的表达。综上所述，这些结果表明，TFLC 能够通过抑制腹腔巨噬细胞中起始的 IRE1/mTORC1/TNF-α 调节的炎症反应，以剂量依赖的方式改善佐剂诱导的关节炎。
