benzofurans and shikonin

Topics: Antineoplastic Agents; Apoptosis; Benzofurans; Binding Sites; Cell Line, Tumor; Cell Movement; Cell Proliferation; Drug Screening Assays, Antitumor; G2 Phase Cell Cycle Checkpoints; Human Umbilical Vein Endothelial Cells; Humans; Molecular Docking Simulation; Naphthoquinones; Protein Binding; Tubulin; Tubulin Modulators

Cell suspension cultures of Lithospermum erythrorhizon produced a large amount of lithospermic acid B, a caffeic acid tetramer, as well as shikonin derivatives (each ca. 10% of dry wt.) when cultured in shikonin production medium M-9. Various culture factors for increasing the production of lithospermic acid B were investigated. Lithospermic acid B production was inhibited by 2, 4-D or NH4+, whereas it was stimulated by Cu2+. These regulatory patterns were similar to those for the production of shikonin derivatives in these cell cultures, suggestive of close relations and similar metabolic regulation between the production of these compounds. Cultivation under light illumination, however, showed that these metabolisms were independently regulated. In particular, blue light showed a stimulatory effect on lithospermic acid B production, while shikonin production was strongly inhibited, indicative of an effective condition for lithospermic acid B production.

Topics: Benzofurans; Cell Culture Techniques; Depsides; Lithospermum; Naphthoquinones; Plant Structures

Lithospermum erythrorhizon cells cultured in pigment production (M-9) medium produced lithospermic acid B, a dimerized caffeic acid ester derivative, in quantities similar to the production of shikonin. The cells also produced a related dimer, (+)-rabdosiin. In Linsmaier-Skoog liquid medium, which suppresses shikonin production, both lithospermic acid B and (+)-rabdosiin were still formed. Lithospermic acid, a caffeic acid-rosmarinic acid conjugate, was isolated as a main constituent in Lithospermum hairy root cultures. In the aerial parts of L. erythrorhizon, the content of these phenylpropanoid oligomers was relatively low compared to that of rosmarinic acid.

Topics: Benzofurans; Caffeic Acids; Cells, Cultured; Depsides; Dimerization; Lignans; Magnetic Resonance Spectroscopy; Naphthoquinones; Plants

A high-performance liquid chromatography (HPLC) analysis system based on a water-acetonitrile gradient program was established for simultaneous quantification of shikimate-derived secondary metabolites in cultured cells of Lithospermum erythrorhizon. The cells cultured in pigment production medium (M-9) are capable of producing five highly hydrophilic compounds such as p-hydroxybenzoic acid-O-glucoside and lithospermic acid B, as well as eleven lipophilic compounds including echinofuran B and acetylshikonin. In addition to the wide polarities of those compounds, many of them are unstable under light, dryness, oxygen and heating. Thus, a new extraction procedure for all these compounds was also established by use of ultrasonication under ice-water chilling with MeOH as the solvent. This procedure was applied to the quantitative analyses of these compounds in cell cultures and hairy root cultures of Lithospermum, and in the intact plants as well.

Topics: Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents, Phytogenic; Benzofurans; Cells, Cultured; Chromatography, High Pressure Liquid; Cold Temperature; Depsides; Furans; Glucosides; Naphthoquinones; Parabens; Plant Roots; Plants, Medicinal; Shikimic Acid; Solvents; Sonication