Caesalpinia sappan L. (Leguminosae) is distributed inSoutheast Asia, and its heartwood, Sappan Lignum, is famous as a red dyestuff. Sappan Lignum is also used as herbal medicine for inflammation or improvement for blood circulation. 1,2) In Japan, Sappan Lignum is newly listed in the 15th Japanese Pharmacopoeia. 3)Aside from brazilin (1) and brazilein, the known constituents of Sappan Lignum, we have isolated sappanchalcone (2) and protosappanins A-E (3-7), which are dibenzoxocin derivatives, and elucidated their structures (Fig. 1). [4][5][6][7][8][9] Pharmacological studies of Sappan Lignum focusing on its vasorelaxation 10) or immunosuppressive effect 11) have concluded that 1 is the active compound. Compound 1 alone was reported to show anti-inflammatory effect, 12,13) lensaldose reductase inhibitory effect, 14) and anti-hepatotoxic effect.15) However, there are few pharmacological studies of other compounds except ours. We previously performed an in vitro assay for 1, brazilein, 2, 3, 4, and 5, and clarified such properties as inhibition of nitric oxide (NO) production and inducible NO synthase gene expression, as well as free radical scavenging and antioxidant activity.16) The results suggested that Sappan Lignum contained active compounds other than 1 that showed anti-inflammatory effect.In this study, we performed an in vitro assay for 2, 4) 3, 5)4, 6) 5, 7) 6 (isomeric mixtures), 8) and 7 (isomeric mixtures of E-1 and E-2) 9) to determine the mechanism underlying their inhibitory effects on NO and prostaglandin E 2 (PGE 2 ) production and their suppressive effects on the mRNA expression of typical chemical mediators of inflammation: tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), and inducible NO synthase (iNOS). We then performed an in vivo assay for methanolic extract of Sappan Lignum (CSE) and 1 to evaluate their anti-inflammatory effect on carrageenin-induced mouse paw edema in order to estimate whether or not 1 was the only active constituent of CSE. MATERIALS AND METHODSMaterials Brazilin (1, 5.1% from CSE), sappanchalcone (2, 0.38%), protosappanin A (3, 0.15%), protosappanin B (4, 0.80%), protosappanin C (5, 0.48%), protosappanin D (6, 0.15%), and protosappanin E (7, 0.32%) were isolated from Sappan Lignum purchased from Uchida Wakanyaku Co., Ltd. (Lot. No. 313116, December 27, 2006 We performed an in vitro assay for seven compounds from methanolic extract of Sappan Lignum (CSE) that inhibit the chemical mediators of inflammation using the J774.1 cell line: brazilin (1), sappanchalcone (2), protosappanin A (3), protosappanin B (4), protosappanin C (5), protosappanin D (6), and protosappanin E (7). Those compounds were evaluated for their inhibitory effects on nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) production and their suppressive effects on tumor necrosis factor-a a (TNF-a a), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) mRNA expression. As a result, we clarified that 1 inhibited NO production, and almost no...

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Intermolecular hydroacylation between salicylaldehydes 1, 26-40 and 1,4-penta- or 1,5-hexadienes 4-13 by Rh-catalyst proceeded under mild reaction conditions to give a mixture of iso- and normal-hydroacylated products 14-25, 41-55, and 57-60. In the hydroacylation reaction, chelation of both salicylaldehyde and diene to the Rh-complex plays a crucial role. The ratio of iso- and normal-hydroacylated products could be regulated by the addition of salicylic acid or amines. The effects of various Rh-complexes, solvents, and additives were examined, and the plausible mechanisms of the catalytic cycle were proposed on the basis of the deuterium-labeling salicylaldehyde experiments.