Lindenane sesquiterpenoid dimers from Chloranthus holostegius with anti-neuroinflammatory activities in BV-2 microglia
Zhao‐Chun Zhan, Yiping Xia, Qing Tang, Huihui Zhu, Jingyi Du, Jun-Xing Cai, Yan-Jun Chen, Zhong‐Nan Wu, Yao-Lan Li, Neng‐Hua Chen, Guo‐Cai Wang, Yubo Zhang
Abstract
Fifteen undescribed lindenane-type sesquiterpenoid dimers, designated chloranholides F−T ( 1 − 15 ), together with twenty-five known analogs ( 16 − 40 ), were isolated from the whole plants of Chloranthus holostegius . The isolate structures were elucidated by analysis of spectroscopic data and chemical methods, and their absolute configurations were determined by X-ray crystallography and electronic circular dichroism spectra. In anti-neuroinflammatory assays, all isolates were evaluated by examination of their inhibitory effect on nitric oxide (NO) in LPS-stimulated BV-2 cells, and the results showed that 21 − 24 , 26 , 30 , 32 and 36 significantly inhibited the production of the inflammatory mediator NO, with IC 50 values ranging from 3.18 to 11.46 μM, which was better than that of quercetin . Structure-activity relationship analysis revealed that two essential functional groups played an indispensable role in the anti-inflammatory effects. Moreover, 22 and 24 inhibited the LPS-induced upregulation of iNOS and COX-2 enzymes in BV-2 microglia at the protein level.