For each concentration gradient, two new compounds from the root bark of Acanthopanax gracilistylus and their inhibitory effects on neutrophil elastase, cyclooxygenase-1, and cyclooxygenase-2 in vitro

Rheumatism encompasses a broad spectrum of diseases with complex clinical manifestations, imposing a significant burden on human health. Acanthopanacis cortex, derived from the dried root bark of Acanthopanax gracilistylus W. W. Smith, has been utilized in the treatment of rheumatic diseases in China for more than 2000 years. In this study, two novel compounds (designated as 1 and 2) and twelve previously known compounds (3–14) were firstly isolated from Acanthopanacis cortex. Compound 1 exhibits an unique conjugation of a dibenzylbutane-type lignan with quinic acid by acylation, which structure that has not been previously reported. In the present study, the absolute configuration of 1 was ascertained through the application of DP4 + probabilistic analysis and electronic circular dichroism (ECD) spectroscopy. Furthermore, a comprehensive evaluation of the inhibitory potential of compounds 1 and 3–14 against two key therapeutic targets - neutrophil elastase (NE) and cyclooxygenase-2 (COX-2) - was conducted. Related results indicate that thirteen compounds exhibit more potent inhibitory effects against COX-2, with IC₅₀ values spanning a concentration range of 0.17–32.9 μM. Compound 1 showed a superior inhibition of both COX-2 and NE. These findings offer valuable insights for the pursuit of natural, selective COX-2 inhibitors.