Targeted isolation of new di/trinormonoterpenoid glucosides as cyclooxygenase-2 inhibitors from Periplocae Cortex...

In this study, two tri- and three dinormonoterpenoid glucosides, named xiangjiapiosides A-E (1-5), were extracted and purified from the ethanol extract of Periplocae Cortex (PC) by employing a combined approach of HP-20 resin, silica gel, ODS, and semi-preparative high performance liquid chromatography (HPLC) under the guidance of molecular networking based on tandem mass spectrometry (MS/MS). The structural determination of these compounds was achieved by conducting detailed spectroscopic analyses involving nuclear magnetic resonance spectroscopy (NMR) and circular dichroism (CD). Anti-inflammatory evaluation revealed that compounds 1, 2, 4, and 5 exerted a significant suppressive effect on the generation of nitric oxide (NO), tumour necrosis factor-alpha (TNF-α), and Interleukin-6 (IL-6), and down-regulated the expression of cyclooxygenase-2 (COX-2). The COX-2 enzyme inhibitory activities of these compounds were notable, and the corresponding IC₅₀ values were 18.82, 41.54, 26.97, and 13.41 μM. Docking analysis results demonstrated that compounds 1, 2, 4, and 5 had the capacity to occupy the catalytic domain of COX-2 enzymes, exhibiting analogous binding conformations to those observed with the selective COX-2 inhibitor celecoxib. All these findings implied that these di/trinormonoterpenoid glucosides derived from PC possess promising characteristics for development as novel COX-2-targeted therapeutic agents.