Characteristic Dihydrophenanthrenes from Spiranthes sinensis with Therapeutic Potential for Ischemic Stroke
Jiaxin Qi, Libin Xu, Yingjie Wang, Lingling Li, Guibin Zhang, Xinyang Liu, Xinfa Ding, Bin Lin, Di Zhou, Yue Hou, Ning LiAbstract
Spiranthes sinensis, known as “Panlongshen”, is an edible traditional Chinese medicine, widely used in herbal teas and health-promoting foods. In this study, we investigated the neuroprotective properties of S. sinensis against ischemic stroke for the first time. Bioactivity-guided isolation yielded 19 dihydrophenanthrenes, including 9 undescribed compounds (7a/7b, 9–11, 12a/12b–13a/13b). These dihydrophenanthrenes demonstrated significant antineuroinflammatory activity against NO production in LPS-induced BV-2 microglia cells, with IC50 values ranging from 1.5 to 34.8 μM, which were greater than that of the positive drug (minocycline, IC50: 34.9 μM). Furthermore, coelonin (2) reduced inflammatory cytokines in BV-2 microglia and preserved PC12 cells’ viability under oxygen-glucose deprivation/reoxygenation. Mechanistic investigations revealed that coelonin (2) exerts its antineuroinflammatory effects by targeting MAP3K7 and suppressing the NF-κB signaling cascade. In vivo, coelonin alleviated ischemic-reperfusion injury after MCAO. These findings revealed the neuroprotective and anti-ischemic stroke effects of S. sinensis and identified dihydrophenanthrenes as its key active constituents.