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

• Published in: Chinese journal of chemistry 2024-06, Vol.42 (11), p.1247-1259
• Main Authors: Feng, Wei‐Jiao, Gu, Yue, Huang, Pei‐Zhi, Yang, Hong‐Ying, Zhang, Rui, He, Yi‐Lin, Lv, Ting‐Hong, Li, Ya, Gao, Kun
• Format: Article
• Language: English
• Subjects: Alanine; Alanine transaminase; Anti‐inflammatory activity; Aspartate aminotransferase; Chloranthus japonicus; Cholesterol; Crystallography; Dimers; Fatty-acid synthase; Inflammation; Lindenane‐type sesquiterpenoid dimers; Lipids; Lipid‐lowering activity; Lipopolysaccharides; Macrophages; Natural products; NMR spectroscopy; Proteins; Scaffolds; Transaminases; Triglycerides; X‐ray diffraction
• ISSN: 1001-604X; 1614-7065
• DOI: 10.1002/cjoc.202300731

Comprehensive Summary 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 μmol/L. Seventeen new lindenane sesquiterpenoid dimers (LSDs), chlorajaponins A—Q (1—17), including two rearranged skeleton meroterpenoids (1—2), and 13 reported analogs (18—30) were isolated from the Chloranthus japonicus Sieb. Compounds 1, 2, and 18 demonstrated significant inhibitory effects on lipid accumulation, dose‐dependently reduced TG and TC levels, and significantly downregulated expression of FASN and SERBP1 validated by western blot assay. Moreover, compounds 19—22 and 25 exhibited the most potent anti‐inflammatory effects with IC50 values of 7.89, 6.25, 2.98, 10.77, and 3.60 μmol/L, respectively.