Chlorajaponins A-Q, Lindenane-Related Sesquiterpenoid Dimers from Chloranthus japonicus and Their Biological Activities

Seventeen undescribed lindenane-related sesquiterpenoid dimers, chlorajaponins A-Q (1-17), and 13 reported analogs (18-30) were isolated from Chloranthus japonicus Sieb. Compound 1 possesses an unprecedented 3/5/7/5/5/6/5/3 fused octacyclic scaffold, featuring a 6(5 -> 4)-abeo-lindenane monomer, while 2 exhibits a 3/5/6/6/5/6/5/3 fused octacyclic scaffold. Their structures were determined through a combination of spectroscopic analyses and X-ray crystallography. Compounds 1, 2, and 18 demonstrated significant inhibitory effects on lipid accumulation and effectively reduced the levels of triglycerides and total cholesterol, as well as the levels of aspartate aminotransferase and alanine aminotransferase in a HepG2 cell model. In addition, compounds 1, 2, and 18 significantly suppressed the protein expression of the fatty acid synthase (FASN) and the sterol regulatory element-binding protein 1 (SREBP1). Moreover, the anti-inflammatory assay showed that compounds 19-22 and 25 inhibited the NO production induced by lipopolysaccharide in RAW 264.7 macrophages with IC50 values of 7.89 +/- 0.44, 6.25 +/- 0.46, 2.98 +/- 0.29, 10.77 +/- 0.60, and 3.60 +/- 0.28 mu mol/L.