Phenolic constituents from the rhizomes of Acorus gramineus and their biological evaluation on antitumor and anti-inflammatory activities

On the search for anti-cancer compounds from natural Korean medicinal sources, a bioassay-guided fractionation and chemical investigation of the MeOH extract from the rhizomes of Acorus gramineus resulted in the isolation and identification of thirteen phenolic derivatives (1-13) including two new 8-O-4′-neolignans, named surinamensinols A (1) and B (2) and a new phenolic compound, named acoramol (9). The structures of these new compounds were elucidated on the basis of 1D and 2D NMR spectroscopic data analyses as well as circular dichroism (CD) spectroscopy studies. The cytotoxic activities of the isolates (1-13) were evaluated by determining their inhibitory effects on human tumor cell lines. The new 8-O-4′-neolignans, compounds 1 and 2, showed moderate antiproliferative activities against A549, SK-OV-3, SK-MEL-2, and HCT-15 cell lines with IC₅₀ values in the range of 4.17-26.18 μM. On the basis of the expanded understanding that inflammation is a crucial cause of tumor progression, anti-inflammatory activities of these compounds were determined by measuring nitric oxide (NO) levels in the medium using murine microglia BV-2 cells. Compounds 1, 2, 4, 7 and 10 inhibited NO production in BV-2 stimulated by lipopolysaccharide with IC₅₀ values of 8.17-18.73 μM via NO scavenging, inhibition of iNOS activity, and/or suppression of iNOS expression.