Gao Mengyao, Liu Jun, Li Quansheng, Zhao Yeyu, Jin Xin, Tang Xinyi, Li Congxi, Gao Mingli
Liaoning University of Traditional Chinese Medicine, China.
Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, China.
Heliyon. 2024 Aug 30;10(17):e37257. doi: 10.1016/j.heliyon.2024.e37257. eCollection 2024 Sep 15.
As a commonly used traditional Chinese medicine formula for treating rheumatoid arthritis (RA), Sishen Decoction (SSD) has anti-inflammatory, analgesic and swelling relief effects. However, at present, the pharmacodynamic basis of SSD and its mechanism of treating RA have not been clarified, and further research is needed. Analyzing the pharmacological basis of SSD was the aim of our study and further elucidate its therapeutic mechanism and potential targets for treating RA. LC‒MS was used to identify the high content and characteristic chemical components of SSD. On this basis, a network of pharmacological analysis was established between the chemical structure and RA. According to the predicted possible pathways and targets, pharmacodynamic experiments and related pathway analysis were conducted. Finally, the possible targets and mechanisms of SSD in treating RA were analyzed. Identified 78 compounds from SSD by LC-MS, including 23 flavonoids, 19 phenolic acids, 9 monoterpenoids and 26 other compounds. Network pharmacological analysis based on pharmacodynamic substances revealed that the most likely interaction pathway between SSD and RA was the PI3K/AKT/mTOR pathway. Foot swelling and inflammatory factors (IL-6, IL-10, IL-18, TGF, TNF-α, VEGF) in model mice were shown to be significantly improved . WB and qPCR experiments proved that SSD could significantly regulate the pathway of PI3K/AKT/mTOR. The interaction between SSD and AKT target was further analyzed by multispectroscopy. This study revealed that SSD alleviates RA by regulating the pathway of PI3K/AKT/mTOR and preliminarily revealed the pharmacodynamic mechanism of SSD for the first time.
四神汤（SSD）作为治疗类风湿性关节炎（RA）的常用中药方剂，具有抗炎、镇痛和消肿作用。然而，目前SSD的药效学基础及其治疗RA的机制尚未明确，需要进一步研究。分析SSD的药理基础是本研究的目的，并进一步阐明其治疗机制和治疗RA的潜在靶点。采用液相色谱-质谱联用（LC‒MS）技术鉴定SSD中含量高且具有特征性的化学成分。在此基础上，建立化学成分与RA之间的网络药理学分析。根据预测的可能途径和靶点，进行药效学实验及相关途径分析。最后，分析了SSD治疗RA的可能靶点和机制。通过LC-MS从SSD中鉴定出78种化合物，包括23种黄酮类、19种酚酸类、9种单萜类和26种其他化合物。基于药效物质的网络药理学分析表明，SSD与RA之间最可能的相互作用途径是PI3K/AKT/mTOR途径。模型小鼠的足肿胀及炎症因子（IL-6、IL-10、IL-18、TGF、TNF-α、VEGF）均显著改善。蛋白质免疫印迹（WB）和实时定量聚合酶链反应（qPCR）实验证明，SSD可显著调节PI3K/AKT/mTOR途径。通过多光谱技术进一步分析了SSD与AKT靶点之间的相互作用。本研究表明，SSD通过调节PI3K/AKT/mTOR途径减轻RA，并首次初步揭示了SSD的药效学机制。
