Twelve novel sesquiterpenes with anti-inflammatory and cholesterol-lowering activities from burdock leaves

Nine new cadinane-type sesquiterpenoids (1–9) and three new eucalyptane -type sesquiterpenes (10–12) were isolated from the ethyl acetate extract of Burdock leaves, which were commonly used for preventing or treating atherosclerosis in China. Their structures were confirmed by extensive spectroscopic analysis, single-crystal X-ray diffraction analysis and ECD calculations. Compound 1 possessed the rare large conjugated skeleton. All the isolates were evaluated for anti-inflammatory and cholesterol-lowering activities by the LPS- and oxidized-low-density-lipoprotein-stimulated RAW 264.7 cells, respectively. As the results, all isolates could decrease the productions of NO, and down-regulate the accumulation of cholesterol. Among them, 4 showed the most potent cholesterol-lowering effect. For the high content of 4 in the herb, mechanistic study of 4 was performed and the results showed that 4 markedly reduced the release of pro-inflammatory mediators which was probably associated with inhibition of the PI3K/Akt and 5-LOX signaling pathways. The findings of this study demonstrated the anti-inflammatory/cholesterol-lowering effects of the new sesquiterpenes from burdock leaves, which provides chemical basis and scientific evidence for the herb used as anti-atherosclerosis agents for the further study. The sesquiterpene lactones of burdock leaves are expected to become new small molecule inhibitors for the treatment of AS.