Ouyang Xiang, Li Na-Zhi, Guo Min-Xia, Zhang Man-Man, Cheng Jie, Yi Li-Tao, Zhu Ji-Xiao
Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine, Jiangxi University of Chinese Medicine, Nanchang, China.
Department of Chemical and Pharmaceutical Engineering, Huaqiao University, Xiamen, China.
Front Pharmacol. 2021 Nov 5;12:760331. doi: 10.3389/fphar.2021.760331. eCollection 2021.
Maxim is a characteristic herb commonly used in Tibetan medicine. Tibetan medicine records it as an important medicine for the clinical treatment of "Yellow Water Disease," the symptoms of which are similar to that of arthritis. Our previous study showed that the flavonoid fraction extracted from could attenuate hyperuricemia. However, the effects of the active flavonoids on gouty arthritis remain elusive, and the underlying mechanism is not understood. In the present study, the effects of the active flavonoids were evaluated in rats or Raw264.7 cells with gouty arthritis induced by monosodium urate (MSU) crystal, followed by the detection of TLR4, MyD88, pNF-κB, and NLR family pyrin domain-containing 3 (NLRP3) expression. The swelling of the ankle joint induced by MSU crystal began to be relieved 6 h post the administration with the active flavonoids. In addition, the active flavonoids not only alleviated MSU crystal-induced inflammation in synovial tissues by histopathological examination but also reduced tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) levels in the joint tissue fluid of MSU crystal-induced rats. Furthermore, Western blot analysis indicated that the active flavonoids reduced the production of these cytokines by inhibiting the TLR4/MyD88/NF-κB pathway and decreasing NLRP3 expression in synovial tissues of rats. More importantly, the inhibition of TLR4/MyD88/NF-κB pathway and NLRP3 expression was also confirmed in MSU-induced Raw264.7 cells. In conclusion, these results indicated that the active flavonoids from could effectively attenuate gouty arthritis induced by MSU crystal through the TLR4/MyD88/NF-κB pathway and NLRP3 expression and , suggesting several potential candidates for the treatment of gouty arthritis.
藏红花是藏药中常用的特色药材。藏药将其记载为临床治疗“黄水病”的重要药物，该病症状与关节炎相似。我们之前的研究表明，从藏红花中提取的黄酮类成分可减轻高尿酸血症。然而，活性黄酮对痛风性关节炎的作用仍不明确，其潜在机制也不清楚。在本研究中，我们在尿酸钠（MSU）晶体诱导的痛风性关节炎大鼠或Raw264.7细胞中评估了活性黄酮的作用，随后检测了Toll样受体4（TLR4）、髓样分化因子88（MyD88）、磷酸化核因子κB（pNF-κB）和含NOD样受体家族吡咯结构域蛋白3（NLRP3）的表达。给予活性黄酮6小时后，MSU晶体诱导的踝关节肿胀开始缓解。此外，通过组织病理学检查发现，活性黄酮不仅减轻了MSU晶体诱导的滑膜组织炎症，还降低了MSU晶体诱导的大鼠关节组织液中肿瘤坏死因子α（TNF-α）和白细胞介素-1β（IL-1β）的水平。此外，蛋白质印迹分析表明，活性黄酮通过抑制TLR4/MyD88/NF-κB通路并降低大鼠滑膜组织中NLRP3的表达，减少了这些细胞因子的产生。更重要的是，在MSU诱导的Raw264.7细胞中也证实了对TLR4/MyD88/NF-κB通路和NLRP3表达的抑制作用。总之，这些结果表明，藏红花中的活性黄酮可通过TLR4/MyD88/NF-κB通路和NLRP3表达有效减轻MSU晶体诱导的痛风性关节炎，提示其可能是治疗痛风性关节炎的潜在候选药物。
