Secoiridoids from the Seed of Gonocaryum calleryanum and Their Inhibitory Potential on LPS-Induced Tumor Necrosis Factor and Nitric Oxide Production

Abstract

Three new secoiridoid constituents, goncarin A−C (1–3), and a new derivative, goncarin A monoacetate (4), along with two known lignins, pinoresinol (5) and paulownin (6), were isolated from the seed of Gonocaryum calleryanum (Baill.) Becc. The structures of the new metabolites were determined on the basis of extensive spectroscopic analysis, particularly mass spectroscopy and 2D NMR (¹H–¹H COSY, HMQC, HMBC, and NOESY) spectroscopy. The aim of this study was to identify the anti-inflammatory effects of compounds 1–6 on lipopolysaccharide (LPS)-stimulated murine macrophage cell lines (RAW 264.7). Following stimulation with LPS, elevated levels of nitric oxide (NO) production were detected in RAW 264.7 cells; however, pretreatment with compounds 1–6 significantly inhibited the production of NO (around 40–80%, p < 0.01–0.05), by suppressing the expression of inducible NO synthase (iNOS). In addition, LPS-stimulated tumor necrosis factor-α (TNF-α) production was significantly reduced by compounds 1–3 (25–40%, p < 0.01–0.05). These results suggested that compounds 1–3 may exert anti-inflammatory activity, and that compounds 1–3 may be considered a potential therapeutic for the treatment of inflammatory diseases associated with macrophage activation.