A new phenyldihydronaphthalene-type lignan, vitexdoin A (1), a new phenylnaphthalene-type lignan alkaloid, vitedoamine B (2), four new phenylnaphthalene-type lignans, vitexdoins B-E (3-6), and four known lignan derivatives (7-10) were isolated from Vitex negundo seeds. Their structures were elucidated by detailed analyses of NMR, IR, and MS data. The ability of the isolates to prevent nitric oxide (NO) production by LPS-stimulated RAW 264.7 macrophages in a concentration-dependent manner was also studied. Compounds 5, 6, and 9 were among the most potent NO production inhibitors, with IC(50) values of 0.13, 0.15, and 0.11 microM, respectively. The introduction of free hydroxy groups plays a vital role in the potency of these compounds.