Anti-inflammatory and anti-osteoporotic lignans from Vitex negundo seeds

Chemical investigation of Vitex negundo seeds afforded four new lignans, including a phenylindene-type lignan, vitexdoin F (1), and three phenylnaphthalene-type lignans, vitexdoins G, H and I (2-4). Their structures were elucidated by detailed spectroscopic analyses on the basis of NMR, IR, and MS data. All compounds were evaluated for their anti-inflammatory and anti-osteoporotic activities, employing RAW264.7 macrophages, osteoblast-like UMR106 and osteoclastic cells, respectively. Compound 1 showed significant inhibition on the nitric oxide (NO) production (IC₅₀ 4.17 μg/mL) due to its down-regulation of the inducible nitric oxide synthase (iNOS) protein expression in LPS-stimulated RAW264.7 cells, which also exhibited potent stimulatory effects on the proliferation and ALP (alkaline phosphatase) activity of UMR106 cells, and significantly up-regulated the OPG/RANKL protein ratio.