Wang Yuming, Zhang Fangfang, Li Xiaokai, Li Xue, Wang Jiayi, He Junjie, Wu Xiaoyan, Chen Siyu, Zhang Yanjun, Li Yubo
School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
ACS Omega. 2023 Mar 20;8(12):11138-11150. doi: 10.1021/acsomega.2c07959. eCollection 2023 Mar 28.
The Simiao pill (SMP) is a classic prescription that has shown anti-inflammatory, analgesic, and immunomodulatory effects and is clinically used to treat inflammatory diseases, such as rheumatoid arthritis (RA) and gouty arthritis, for which the effects and mechanism of action remain largely unknown. In this study, serum samples from RA rats were analyzed using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry based metabolomics technology and liquid chromatography with tandem mass spectrometry proteomics technology together with network pharmacology to explore the pharmacodynamic substances of SMP. To further verify the above results, we constructed a fibroblast-like synoviocyte (FLS) cell model and administered phellodendrine for the test. All these clues suggested that SMP can significantly reduce the level of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in complete Freund's adjuvant rat serum and improve the degree of foot swelling; combined with metabolomics, proteomics, and network pharmacological technology, it is determined that SMP plays a therapeutic role through the inflammatory pathway, and phellodendrine is found to be one of the pharmacodynamic substances. By constructing an FLS model, it is further determined that phellodendrine could effectively inhibit the activity of synovial cells and reduce the expression level of inflammatory factors by downregulating the expression level of related proteins in the TLR4-MyD88-IRAK4-MAPK signal pathway to alleviate joint inflammation and cartilage injury. Overall, these findings suggested that phellodendrine is an effective component of SMP in the treatment of RA.
四妙丸（SMP）是一种经典方剂，已显示出抗炎、镇痛和免疫调节作用，临床上用于治疗类风湿性关节炎（RA）和痛风性关节炎等炎症性疾病，但其作用效果和作用机制在很大程度上仍不清楚。在本研究中，采用基于超高效液相色谱-四极杆飞行时间质谱的代谢组学技术和液相色谱串联质谱蛋白质组学技术，并结合网络药理学，对RA大鼠的血清样本进行分析，以探索SMP的药效物质。为进一步验证上述结果，我们构建了成纤维样滑膜细胞（FLS）模型，并给予黄柏碱进行试验。所有这些线索表明，SMP可显著降低完全弗氏佐剂大鼠血清中白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的水平，并改善足肿胀程度；结合代谢组学、蛋白质组学和网络药理学技术，确定SMP通过炎症途径发挥治疗作用，且黄柏碱是药效物质之一。通过构建FLS模型，进一步确定黄柏碱可有效抑制滑膜细胞活性，并通过下调TLR4-MyD88-IRAK4-MAPK信号通路中相关蛋白的表达水平来降低炎症因子的表达水平，从而减轻关节炎症和软骨损伤。总体而言，这些研究结果表明黄柏碱是SMP治疗RA的有效成分。
