地枫皮入血成分抗类风湿性关节炎作用研究

Study on the anti-rheumatoid arthritis effect of entering bloodstream components from Illicium difengpi

关键词:  地枫皮，异红花八角醇，类风湿性关节炎，入血，液相色谱-串联质谱法，TLR4/NF-κB通路

Key words:  Illicium difengpi, isodunnianol, rheumatoid arthritis, enter the bloodstream, LC-MS/MS, TLR4/NF-κB pathway

摘要:

为发现地枫皮中具有抗类风湿性关节炎（RA）功效的化合物，该研究利用液相色谱-串联质谱法鉴定地枫皮的入血成分；通过检测入血成分对胶原诱导的关节炎小鼠表观病症，关节炎指数，膝关节病理，以及血清中MCP-1、IL-6和TNF-α含量的影响，评价入血成分的抗RA活性；利用分子对接的方法，探究抗RA活性化合物与TLR4/NF-κB通路的相互作用。结果表明：（1）地枫皮中的异红花八角醇、厚朴酚能够进入血浆。（2）异红花八角醇能够缓解胶原诱导关节炎小鼠的四肢充血、发红、肿胀等症状，减小关节炎指数，阻碍膝关节组织病理进程，降低血清中MCP-1、IL-6和TNF-α含量。（3）异红花八角醇能够与TLR4/NF-κB通路中的关键蛋白质TLR4、IκBα和NF-κB p65结合。总之，异红花八角醇被吸收后，通过血液循环到达关节组织，可能影响TLR4/NF-κB通路而缓解RA病症，是地枫皮抗RA的活性成分之一。

Abstract:

To search the compounds that can relieve rheumatoid arthritis from Illicium difengpi, the components that can enter bloodstream were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and then their anti-rheumatoid arthritis activities were evaluated by testing their effects on symptoms, arthritis indexes, pathological changes of knee joints, and contents of MCP-1, IL-6 and TNF-α in serum of collagen-induced arthritis mice. The potential interactions between the anti-rheumatoid arthritis compounds and TLR4/NF-κB pathway were studied by molecular docking. The results were as follows: (1) After absorbance, isodunnianol and magnolol could enter bloodstream. (2) Isodunnianol could alleviate symptoms including limb congestion, redness and swelling, reduce arthritis index score of limbs, improve histopathology of knee joints, and decrease contents of MCP-1, IL-6 and TNF-α in serum of collagen-induced arthritis mice. (3) Isodunnianol could bind to key proteins of TLR4/NF-κB pathway, including TLR4, IκBα and NF-κB p65. In conclusion, isodunnianol could enter bloodstream after absorbance and alleviate the pathology of rheumatoid arthritis, possibly through regulating TLR4/NF-κB pathway. Therefore, isodunnianol is one of anti-rheumatoid arthritis active components of Illicium difengpi.