Increasing scientific evidence has demonstrated that the roots of Polygala tenuifolia Willd. have pharmacological effects related to anti-inflammation. Therefore, the aim of this study is to investigate the chemical constituents from P. tenuifolia roots as anti-inflammatory drug candidates. In the present work, twenty-three compounds were isolated from P. tenuifolia roots, including three saponins (1-3), ten phenylpropanoid sucrose esters (4-12), one benzoic acid sugar ester derivative (13), four xanthones (14-17), two hydroxy benzophenone derivatives (18 and 19), two phenolic derivatives (20 and 21), and two ionones (22 and 23). All isolates were tested for their inhibitory effects of LPS-stimulated NO and PGE2 production in RAW 264.7 macrophages. Among these, 3-O-(3,4,5-trimethoxy-cinnamoyl),6'-O-(p-methoxybenzoyl) sucrose ester (TCMB; 11) together with compounds 3 and 21 exhibited significant inhibitory effects on NO production, while TCMB and compounds 17, 19, and 21 showed strong inhibitory effects on PGE2 production. Specifically, TCMB (11) downregulated the protein levels of iNOS and COX-2 in LPS-induced RAW 264.7 macrophages. In addition, TCMB (11) dose-dependently diminished the relative mRNA expression levels of iNOS, PGE2, and proinflammatory cytokines (TNF-α, IL-1β, and IL-6). A molecular docking study showed that TCMB (11) has strong binding affinities with iNOS and COX-2.
Keywords: Polygala tenuifolia; inflammation; nitric oxide; oligosaccharide ester; proinflammatory mediators; prostaglandin E2.