Characteristic Dihydrophenanthrenes from Spiranthes sinensis with Therapeutic Potential for Ischemic Stroke

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.