State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, People's Republic of China; Tianjin International Joint Academy of Biomedicine, Tianjin 300070, People's Republic of China.
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, People's Republic of China.
Fitoterapia. 2024 Sep;177:106088. doi: 10.1016/j.fitote.2024.106088. Epub 2024 Jun 17.
Ligularia fischeriTurcz. is a medicinal plant for the treatment of inflammation in China and Korea. Its chemical components in anti-sepsis activity and the related molecular mechanisms remain unknown yet. In this study, two undescribed eremophilane sesquiterpenoids fischerins A (1) and B (2), together with 8 known sesquiterpenoid derivatives (3-10), were isolated from the whole plant of L. fischeri. Their structures were identified by detailed spectroscopic and ECD analyses. 3-Oxo-8-hydroxyeremophila-1,7(11)-dien-12,8-olide (6) showed the most inhibitory effect on NO production in LPS-stimulated RAW 264.7 cells with the IC value of 6.528 μM. Meanwhile, compound 6 also decreased the mRNA expression of pro-inflammatory factors IFN-γ, IL-1β, IL-6 and TNF-α via downregulating NF-κB signaling pathway in vitro. Furthermore, compound 6 reduced the mortality, murine sepsis score, the serum TNF-α level and organic damage in a mouse model of sepsis. These findings indicated that compound 6 possessed the potent anti-inflammatory activity and had the potential as a promising drug candidate for sepsis therapy.
川木香是一种在中国和韩国用于治疗炎症的药用植物。其在抗败血症活性方面的化学成分和相关分子机制尚不清楚。在这项研究中，从川木香的全植物中分离得到了两种未被描述的半日花烷倍半萜 Fischerins A（1）和 B（2），以及 8 种已知的倍半萜衍生物（3-10）。通过详细的光谱和 ECD 分析确定了它们的结构。3-氧代-8-羟基半日花-1,7(11)-二烯-12,8-内酯（6）在 LPS 刺激的 RAW 264.7 细胞中对 NO 产生的抑制作用最强，IC 值为 6.528 μM。同时，化合物 6 通过下调 NF-κB 信号通路，还降低了体外促炎因子 IFN-γ、IL-1β、IL-6 和 TNF-α的 mRNA 表达。此外，化合物 6 降低了败血症小鼠模型的死亡率、小鼠败血症评分、血清 TNF-α 水平和器官损伤。这些发现表明，化合物 6 具有很强的抗炎活性，有可能成为治疗败血症的有前途的药物候选物。
