State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin 301617, China.
Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin 301617, China.
Molecules. 2024 Aug 7;29(16):3751. doi: 10.3390/molecules29163751.
The occurrence of inflammation is closely related to the activation of the NLRP3 inflammasome. IL-1β produced during the activation of the NLRP3 inflammasome has strong pro-inflammatory activity and can also promote the release of inflammatory factors by other immune cells, exacerbating inflammatory damage to tissues. Utilizing IL-1β as the detection index to find small-molecule inhibitors targeting NLRP3 from natural products will benefit the search for drugs for inflammation-related diseases. During the exploration of anti-inflammatory active components derived from the flowers of L., an ingredient in traditional Chinese medicine with dual applications in both medicinal treatment and dietary consumption, fourteen compounds (-), including seven previously unreported ones, named flosdolilabnitrogenousols A-D (-) and flosdolilabsaponins A-C (-), were found. Their structures were established through extensive NMR spectra determination, HR-ESI-MS analysis, ECD calculations, and chemical reactions. Flosdolilabsaponin A () stands out as an exceptionally rare tetracyclic lactone oleane-type saponin. Additionally, the inhibitory activity on IL-1β release of all compounds, without cytotoxicity, was evaluated using BMDMs stimulated with LPS/Nigericin. An Elisa assay revealed that compounds , , , and - exhibited significant inhibition of IL-1β release at a concentration of 30 μM. Structure-activity relationships were also discussed. This study indicates that flowers possess anti-inflammatory activity, which might exert its effect by suppressing the activation of the NLRP3 inflammasome.
炎症的发生与 NLRP3 炎性小体的激活密切相关。NLRP3 炎性小体激活过程中产生的 IL-1β 具有很强的促炎活性，同时还能促进其他免疫细胞释放炎症因子，加重组织的炎症损伤。利用 IL-1β 作为检测指标，从天然产物中寻找针对 NLRP3 的小分子抑制剂，将有利于寻找与炎症相关疾病的药物。在对具有药用和食用双重应用的传统中药金银花的抗炎活性成分进行探索时，发现了 14 种化合物（-），包括 7 种以前未报道过的化合物，分别命名为 flosdolilabnitrogenousols A-D（-）和 flosdolilabsaponins A-C（-）。通过广泛的 NMR 谱测定、HR-ESI-MS 分析、ECD 计算和化学反应，确定了它们的结构。Flosdolilabsaponin A（-）是一种极为罕见的四环内酯齐墩果烷型皂苷。此外，还通过 LPS/Nigericin 刺激的 BMDMs 评估了所有化合物（无细胞毒性）对 IL-1β 释放的抑制活性。ELISA 检测结果表明，化合物 -、-、-和-在 30 μM 浓度下对 IL-1β 的释放具有显著抑制作用。还讨论了构效关系。本研究表明，金银花具有抗炎活性，可能通过抑制 NLRP3 炎性小体的激活发挥作用。
