Liang Xu, Gong Qi, Xu Yuting, Mu Jiaxing, Tang Chunping, Hu Bintao, Ke Changqiang, Yao Sheng, Zhang Haiyan, Ye Yang
School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.
State Key Laboratory of Drug Research, Natural Products Chemistry Department, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Molecules. 2025 Mar 31;30(7):1553. doi: 10.3390/molecules30071553.
Hesse ex Rehd. is an endemic plant in China and has long been used as a traditional medicine in several provinces. Although the plant has been reported to contain flavonoids, triterpenes, and alkaloids, this study represents the first report of the isolation of phyllocladane-type diterpenoids, a relatively rare class of compounds. In this study, 18 new phyllocladane-type diterpenoids (-) were isolated and structurally elucidated, including eight uncommon 3,4- phyllocladane-type diterpenoids (-) and two unusual phyllocladane-type diterpene dimers (-), along with six known analogues (-). Their structures were elucidated by a comprehensive analysis of 1D and 2D NMR, IR, and HRESIMS data. The absolute configurations were determined by single crystal X-ray diffraction experiments, DFT NMR calculations, and TDDFT ECD calculations. Based on the obtained and reported spectroscopic data, we refined a rule to distinguish phyllocladane-type diterpenoids from their diastereomeric -kaurane-type compounds. Additionally, the isolated compounds were evaluated for their in vitro anti-neuroinflammatory activity against lipopolysaccharide (LPS)-induced inflammation in BV-2 microglial cells. Compounds , , , , , and showed moderate inhibitory activity at the concentration of 20 μM, with compounds and markedly reducing the mRNA levels of the pro-inflammatory cytokines IL-1, IL-6, and TNF- at this concentration.
黑塞异叶柳是中国的一种本土植物，长期以来在多个省份被用作传统药物。尽管该植物已被报道含有黄酮类、三萜类和生物碱类成分，但本研究首次报道了叶状枝烷型二萜类化合物的分离，这是一类相对罕见的化合物。在本研究中，分离并鉴定了18种新的叶状枝烷型二萜类化合物（-），包括8种不常见的3,4-叶状枝烷型二萜类化合物（-）和2种不寻常的叶状枝烷型二萜二聚体（-），以及6种已知类似物（-）。通过对一维和二维核磁共振、红外光谱和高分辨电喷雾电离质谱数据的综合分析确定了它们的结构。通过单晶X射线衍射实验、密度泛函理论核磁共振计算和含时密度泛函理论电子圆二色计算确定了绝对构型。基于获得的和已报道的光谱数据，我们完善了一条规则，以区分叶状枝烷型二萜类化合物与其非对映异构体-贝壳杉烷型化合物。此外，对分离得到的化合物进行了体外抗神经炎症活性评估，检测其对脂多糖（LPS）诱导的BV-2小胶质细胞炎症的作用。化合物 、 、 、 、 和 在20 μM浓度下表现出中等抑制活性，化合物 和 在该浓度下显著降低促炎细胞因子IL-1、IL-6和TNF-的mRNA水平。
