Zhang Juan, Yan Jiankun, Dong Hongjun, Zhang Rui, Chang Jing, Feng Yanli, Xu Xinrong, Li Wei, Qiu Feng, Sun Chengpeng
School of Chinese Materia Medica, Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang 050200, China.
Chin J Nat Med. 2025 Aug;23(8):961-971. doi: 10.1016/S1875-5364(25)60931-9.
In continuation of research aimed at identifying anti-inflammatory agents from natural sesquiterpenoids, an activity-guided fractionation approach utilizing lipopolysaccharide (LPS)-mediated RAW264.7 cells was employed to investigate chemical constituents from Inula Britannica (I. britannica). Seven novel sesquiterpenoid dimers inulabritanoids A-G (1-7) and two novel sesquiterpenoid monomers inulabritanoids H (8) and I (9) were isolated from I. britannica together with eighteen known compounds (10-27). The structural elucidation was accomplished through comprehensive analysis of 1D and 2D nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS), and electronic circular dichroism (ECD) spectra, complemented by quantum chemical calculations. Compounds 1, 2, 12, 16, 19, and 26 demonstrated inhibitory effects on NO production, with IC values of 3.65, 5.48, 3.29, 6.91, 3.12, and 5.67 μmol·L, respectively. Mechanistic studies revealed that compound 1 inhibited IκB kinase β (IKKβ) phosphorylation, thereby blocking nuclear factor κB (NF-κB) nuclear translocation, and activated the kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signal pathway, leading to decreased expression of NADPH oxidase 2 (NOX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), IL-1β, and IL-1α and increased expression of NAD(P)H: quinone oxidoreductase 1 (NQO-1) and heme oxygenase-1 (HO-1), thus exhibiting anti-inflammatory effects in vitro. These results indicate that dimeric sesquiterpenoids may serve as promising candidates for anti-inflammatory drug development.
为了继续从天然倍半萜类化合物中寻找抗炎剂，采用了一种利用脂多糖（LPS）介导的RAW264.7细胞的活性导向分级分离方法，来研究大花旋覆花（Inula Britannica）中的化学成分。从大花旋覆花中分离出了7个新型倍半萜二聚体旋覆花素A - G（1 - 7）、2个新型倍半萜单体旋覆花素H（8）和I（9），以及18个已知化合物（10 - 27）。通过对一维和二维核磁共振（NMR）、高分辨质谱（HR-MS）和电子圆二色光谱（ECD）进行综合分析，并辅以量子化学计算，完成了结构解析。化合物1、2、12、16、19和26对一氧化氮（NO）的产生具有抑制作用，其IC50值分别为3.65、5.48、3.29、6.91、3.12和5.67 μmol·L-1。机制研究表明，化合物1抑制IκB激酶β（IKKβ）的磷酸化，从而阻断核因子κB（NF-κB）的核转位，并激活kelch样ECH相关蛋白1（Keap1）/核因子红细胞2相关因子2（Nrf2）信号通路，导致NADPH氧化酶2（NOX-2）、诱导型一氧化氮合酶（iNOS）、肿瘤坏死因子α（TNF-α）、白细胞介素-6（IL-6）、单核细胞趋化蛋白-1（MCP-1）、IL-1β和IL-1α的表达降低，以及NAD(P)H：醌氧化还原酶1（NQO-1）和血红素加氧酶-1（HO-1）的表达增加，从而在体外表现出抗炎作用。这些结果表明，二聚倍半萜类化合物可能是有前景的抗炎药物开发候选物。
