State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Chin J Nat Med. 2017 Sep;15(9):674-679. doi: 10.1016/S1875-5364(17)30096-1.
Microglial activation and resultant neuroinflammatory response are implicated in various brain diseases including Alzheimer's disease and Parkinson's disease. Treatment with anti-neuroinflammatory agents could provide therapeutic benefits for such disorders. Protosappanin A (PTA) is a major bioactive ingredient isolated from Caesalpinia sappan L.. In this work, the anti-neuroinflammatory effects of PTA on LPS-stimulated BV2 cells were investigated and the underlying mechanisms were explored. Results showed that PTA significantly inhibited the production of TNF-α and IL-1β in LPS-activated BV2 microglia. Moreover, the mRNA expressions of IL-6, IL-1β, and MCP-1 were reduced by PTA in a dose-dependent manner. Furthermore, PTA suppressed JAK2/STAT3-dependent inflammation pathway through down-regulating the phosphorylation of JAK2 and STAT3, as well as STAT3 nuclear translocation against LPS treatment. These observations suggested a novel role for PTA in regulating LPS-induced neuroinflammatory injuries.
小胶质细胞激活和随之产生的神经炎症反应与各种脑部疾病有关，包括阿尔茨海默病和帕金森病。使用抗神经炎症药物治疗可能对这些疾病有益。原苏木素 A（PTA）是从苏木（Caesalpinia sappan L.）中分离得到的主要生物活性成分。在这项工作中，研究了 PTA 对 LPS 刺激的 BV2 细胞的抗神经炎症作用，并探讨了其潜在机制。结果表明，PTA 可显著抑制 LPS 激活的 BV2 小胶质细胞中 TNF-α和 IL-1β的产生。此外，PTA 以剂量依赖的方式降低了 IL-6、IL-1β和 MCP-1 的 mRNA 表达。此外，PTA 通过下调 JAK2 和 STAT3 的磷酸化以及 STAT3 核转位，抑制了 JAK2/STAT3 依赖性炎症通路，从而抑制了 LPS 诱导的神经炎症损伤。这些观察结果表明 PTA 在调节 LPS 诱导的神经炎症损伤方面具有新的作用。
