Cheng Yexin, Li Hailong, Wu Dan, Hu Yayue, Li Jinhe, Yang Ying, Li Jiahang, Zhou Honggang, Zhang Hongfeng, Xie Chunfeng, Yang Cheng
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.
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; High-throughput Molecular Drug Screening Centre, Tianjin International Joint Academy of Biomedicine, Tianjin 300070, People's Republic of China.
Phytochemistry. 2023 Oct;214:113797. doi: 10.1016/j.phytochem.2023.113797. Epub 2023 Jul 24.
Two undescribed polyoxygenated seco-cyclohexene derivatives named macclureins A and B, and three undescribed polyoxygenated cyclohexene derivatives macclureins C-E, together with 15 known analogues were isolated from the twigs and leaves of Uvaria macclurei. Their structures were established by extensive spectroscopic and circular dichroism analyses. Macclurein C is a chlorinated polyoxygenated cyclohexene. All isolates were evaluated for their anti-inflammatory activities on NO generation in the LPS-stimulated RAW 264.7 cells. (-)-Zeylenone showed the most potent effect against NO production with the IC value of 20.18 μM. Meanwhile, (-)-zeylenone also decreased the mRNA expression of pro-inflammatory factors IFN-γ, iNOS, IL-6 and TNF-α via downregulating NF-κB signaling pathway. Further in vivo experiments using a mouse model of sepsis showed that (-)-zeylenone significantly alleviated sepsis severity by measuring weight, murine sepsis score, survival rate and the serum levels of pro-inflammatory factors TNF-α and IL-6.
从紫玉盘的嫩枝和叶子中分离出两种未描述的多氧化裂环环己烯衍生物,命名为紫玉盘素A和B,以及三种未描述的多氧化环己烯衍生物紫玉盘素C - E,还有15种已知类似物。通过广泛的光谱和圆二色性分析确定了它们的结构。紫玉盘素C是一种氯化多氧化环己烯。评估了所有分离物对脂多糖刺激的RAW 264.7细胞中一氧化氮生成的抗炎活性。(-)-紫穗槐二烯对一氧化氮生成的抑制作用最强,IC值为20.18 μM。同时,(-)-紫穗槐二烯还通过下调核因子κB信号通路降低促炎因子干扰素-γ、诱导型一氧化氮合酶、白细胞介素-6和肿瘤坏死因子-α的mRNA表达。使用脓毒症小鼠模型进行的进一步体内实验表明,通过测量体重、小鼠脓毒症评分、存活率以及促炎因子肿瘤坏死因子-α和白细胞介素-6的血清水平,(-)-紫穗槐二烯显著减轻了脓毒症的严重程度。