Novel phthalide derivatives from the rhizomes of Ligusticum chuanxiong and their inhibitory effect against lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophage cells

Abstract

Five new phthalide derivatives, chuanxiongnolides L1–L5 (1–5), together with three known phthalide dimers (6–8), were isolated from the rhizomes of Ligusticum chuanxiong Hort.. Compound 1 represents a novel type of phthalide derivative, biogenetically derived from coniferyl alcohol and ligustilide. Compound 2 is the first example of an E-ring expanded phthalide dimer with a 5/6/6/6/6 fused-ring system, which is different from the 5/6/6/6/5 fused-ring system in normal phthalide dimers. Their structures were established using spectroscopic data, and the absolute configurations were determined by a circular dichroism (CD) exciton chirality method. To confirm the absolute configuration of compound 1, electronic circular dichroism (ECD) calculations were also conducted. Compounds 1, 2, 6, and 7 exhibited inhibitory effects against lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophage cells with half maximal inhibitory concentration (IC₅₀) values ranging from 3.0 to 12.6 μM. Furthermore, plausible biosynthetic routes for 1 and 2 were also proposed.