Anti-inflammatory compounds were investigated from the ethanol extract of the roots and rhizomes of Asarum heterotropoides var. mandshuricum, a traditional Chinese medicine called Xixin and used for pain and inflammatory. Nine new compounds were isolated, including six new lignans, neoasarinin A-C (1-3), neoasarininoside A and B (4 and 5), and asarinin B (7), and one new monoterpene, asarincin A (8), two new amides, asaramid II and III (10 and 11), and one new natural monoterpene, asaricin B (9), along with 37 known compounds (6, 12-47). Their structures and absolute configurations were elucidated on the basis of spectroscopic methods and chemical analyses. This is the first report of the absolute configuration of asarinin A (6). The 8-O-4' neolignans (1-5) were reported in the genus Asarum for the first time. The 15 compounds 17, 19, 22-25, 28, 31, 36, 40, 42, 43, 45-47 were isolated from the genus Asarum, and compounds 16, 32, 33, 37 and 39 were isolated from A. heterotropoides var. mandshuricum for the first time. Thirty-seven of the isolates were evaluated for anti-inflammatory activity against the release of β-glucuronidase in polymorphonuclear leukocytes (PMNs) induced by the platelet-activating factor (PAF), and compounds 1, 4, 7, 8, 14, 17-19, 22, 24, 25, 29, 30, 32, 33, 40-43, 45, and 46 showed potent anti-inflammatory activities in vitro, with 27.9%-72.6% inhibitions at 10-5 mol/L. The results of anti-inflammatory assay suggested that lignans obtained from the CHCl₃ extract might be the main active components of Xixin.
Keywords: 8-O-4′ neolignan; Aristolochiaceae; Asarum heterotropoides var. mandshuricum; amide; anti-inflammatory; lignans; monoterpene.