Anti‐inflammatory properties of <i>ophioglonin</i> derived from the fern <i>Ophioglossum vulgatum</i> L. via inactivating <scp>NF</scp> ‐ <scp>κB</scp> and <scp>MAPK</scp> signaling pathways

Medicinal plants contain bioactive compounds that have therapeutic effects on human health. Ophioglossum vulgatum L. is a representative species of the fern genus Ophioglossum that has anti-inflammatory properties as recognized in folk medicine. Herein, we performed a nitric oxide (NO) assay-guided screening in RAW264.7 cells to investigate the active components of the plant. We found that ophioglonin (OPN), a characteristic homoflavonoid of the genus Ophioglossum, is one of the bioactive components. Therefore, we performed a comparative analysis of the isolated compounds and found that OPN has effects similar to those of isolated dihydroquercetin and luteolin at the concentrations tested. The antioxidant and anti-inflammatory activities of OPN were extensively validated using lipopolysaccharide -stimulated RAW264.7 cells, mouse bone marrow-derived macrophages (BMDMs), and peritoneal exudate macrophages (PEMs). In vivo experiments with a carrageenan-induced mouse paw edema model further confirmed the anti-inflammatory effect of OPN. Additionally, we found that OPN and Ophioglossum vulgatum extracts inhibit the activation of signal transducers, NF-ĸB p65, IĸBα, ERK, p38, and JNK, consistent with the findings of pathway enrichment analysis. This work reinforces the anti-inflammatory properties of Ophioglossum vulgatum and indicates that OPN is a promising therapeutic agent for inflammation-associated disorders. Further clinical evaluations, including clinical trials, would be beneficial to validate the anti-inflammatory properties of OPN.