COX-2 inhibitors from Laportea bulbifera: Structure-activity relationship, kinetic investigation, and molecular...

Cyclooxygenase-2 (COX-2) is a key therapeutic target for inflammation-related diseases. Laportea bulbifera, a valued ethnic medicine traditionally utilized by the Miao and Buyi minorities in Guizhou Province, China, has long been used to dispel wind and eliminate dampness, promote blood circulation, and relieve pain and pruritus. While our group previously clarified the anti-inflammatory constituents of its rhizomes, this study represents the first systematic investigation of the aerial parts. The active ethyl acetate fraction was subjected to further purification, yielding 35 phenolic compounds, including seven pairs of enantiomeric lignans and eight previously undescribed compounds. Structural elucidation was achieved by detailed spectroscopic analyses. The majority of these metabolites showed strong inhibitory effects on COX-2 (IC₅₀ values between 0.25 and 14.58 μM) and had notable DPPH radical scavenging activity (IC₅₀ values between 0.93 and 11.77 μM). Moreover, four structurally distinct molecules demonstrated remarkable selectivity toward COX-2 over COX-1, with selectivity indices ranging from 93 to over 240. Kinetic studies further revealed that compounds (+)-6 and 30 function as mixed-type COX-2 inhibitors. Collectively, this study provides the first evidence that the aerial parts of Laportea bulbifera contain COX-2/COX-1 selective inhibitors, thereby supporting its potential for further pharmacological research and ethnomedicine development.