Four diarylheptanoids were isolated from the leaf of Alnus hirsuta (Betulaceae) and have been assessed for nitric oxide (NO) production inhibitory effects in vitro. Oregonin (1) and hirsutanonol (2) were found to be potent inducible nitric oxide synthase (iNOS) inhibitors. Compounds 1 and 2 showed inhibition of NO synthesis in dose-dependent manners by murine macrophage-like RAW 264.7 cells stimulated with interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS). Their 50% inhibitory concentrations (IC50) were 3.8 and 14.3 microM, respectively. The inhibitory effects of these compounds on NO synthesis were due to suppression of iNOS mRNA expression as determined by Northern blotting.

Nine known diarylheptanoids (1-9) isolated from the barks of Alnus japonica were evaluated for their inhibitory activities on nitric oxide (NO) and prostagrandin E2 (COX-2) production in interferon-gamma (INF-gamma) and lipopolysaccharide (LPS)-activated RAW 264.7 cells in vitro. The NO and COX-2 levels were moderately reduced by the addition of compounds (1-9). Among these compounds, compounds 6 and 8 inhibited NO production in a dose dependent manner with an IC50 of 16.7 and 27.2 microg/mL, respectively (positive control, L-NMMA; 22.8 microg/mL), and compounds 6, 7, 8, and 9 reduced the COX-2 level in a dose dependent manner with an IC50 of 20.7, 25.7, 25.0, and 27.3 microg/mL, respectively (positive control, indomethacin; 26.2 microg/mL). An analysis of the structural activity relationship among these diarylheptanoids suggests that the presence of a keto-enol group in the heptane moiety or a caffeoyl group in the aromatic ring were important for the efficacy on the inhibitory activities of NO and COX-2 production.

Two known diarylheptanoids, oregonin (1), (5S)-1,7-bis-(3,4-dihydroxyphenyl)-heptane-3-one-5-O-beta-D-xylopyranosi de and hirsutanonol (2), (5S)-1,7-bis-(3,4-dihydroxyphenyl)-5-hydroxyheptane-3-one isolated from the bark of Alnus hirsuta var. sibirica, showed significant inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cyclooxygenase-2 (COX-2) expression in immortalized human breast epithelial MCF10A cells.

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Fermentation of Alnus sibirica (AS) stems using Lactobacillus plantarum subsp. argentoratensis was conducted and three compounds isolated from the Alnus species were identified for the first time, 7-(3,4-dihydroxyphenyl)-1-(4-hydroxyphenyl)-heptan-3-one, 1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptan-3-one and 4-(3,4-dihydroxyphenyl)-butan-2-one, along with 14 known compounds. The anti-oxidative and anti-inflammatory abilities of AS and fermented AS (FAS) as well as the isolated phenolic compounds from FAS were investigated. FAS showed stronger anti-oxidative and anti-inflammatory activities than non-fermented AS.