State Key Laboratory of Southwestern Chinese Medicine Resources, and Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, P. R. China.
State Key Laboratory of Phytochemistry and Plant Resources in West China, and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, P. R. China.
J Med Chem. 2024 Jan 11;67(1):513-528. doi: 10.1021/acs.jmedchem.3c01759. Epub 2023 Dec 27.
Intragastric administration of the total sesterterpenoid extract (TSE) of medicinal plant at 2.5 g/kg dose protected mice from LPS-induced sepsis. Phytochemical investigation led to the isolation and identification of 47 leucosceptrane sesterterpenoids (-) including 30 new compounds (-) with complicated oxygenation patterns. Biological screening indicated their immunosuppressive activity via inhibiting IFN-γ secretion and/or proliferation of T cells with different potencies. Mechanism study of compounds , , and revealed that they inhibited the activations of AKT-mTOR, JNK, p38 MAPK or ERK pathway in T cells and macrophages. In addition, compounds and induced G0/G1 cell arrest of T cells. The major component, leucosceptroid N (), significantly lowered the levels of IL-6 and TNF-α in peripheral blood serum, and ameliorated the multiorgan damages of LPS-induced sepsis mice at 25 mg/kg dose. These findings suggest that leucosceptrane sesterterpenoids are a new type of potential immunosuppressive agents for sepsis treatment.
灌胃给予 2.5 g/kg 剂量的药用植物总倍半萜提取物（TSE）可保护 LPS 诱导的脓毒症小鼠。植物化学研究导致分离和鉴定了 47 种白头翁烷倍半萜（-），包括 30 种具有复杂氧化模式的新化合物（-）。生物筛选表明，它们通过抑制 IFN-γ 分泌和/或具有不同效力的 T 细胞增殖具有免疫抑制活性。化合物、和的机制研究表明，它们抑制 T 细胞和巨噬细胞中 AKT-mTOR、JNK、p38 MAPK 或 ERK 通路的激活。此外，化合物和诱导 T 细胞的 G0/G1 细胞停滞。主要成分白头翁内酯 N（）可显著降低外周血血清中 IL-6 和 TNF-α 的水平，并在 25 mg/kg 剂量下改善 LPS 诱导的脓毒症小鼠的多器官损伤。这些发现表明，白头翁烷倍半萜是治疗脓毒症的一种新型潜在免疫抑制剂。
