Diterpenoids with Schistosomula-Killing and Anti-Fibrosis Activities In Vitro from the Leaves of Croton tiglium.

ABSTRACT

The leaves of C. tiglium have been comprehensively researched for their structurally novel bioactive natural compounds, especially those with anti-schistosomiasis liver fibrosis activity, because ethyl acetate extract, which can be extracted from the leaves of C. tiglium, has good anti-schistosomiasis liver fibrosis effects. One new tigliane-type diterpene, 20-acetyl-13-O-(2-metyl)butyryl-phorbol (1), and nine known (2-10) analogues were isolated from the leaves of C. tiglium. Their structures were elucidated on the basis of spectroscopic analysis and ECD analysis. All diterpenoids had a stronger insecticidal effect on schistosomula, and compounds 2, 4, and 10 had good anti-liver-fibrosis effects. Furthermore, compared with the model group, compound 2 significantly downregulated the protein and mRNA expression of COL-I, COL-III, α-SMA, and TGF-ß1 on TGF-ß1-induced liver fibrosis in LX-2 cells. Meanwhile, compound 2 also regulated the expression of TGF-ß/Smad-pathway-related proteins. The results suggest that diterpenoids from C. tiglium may serve as potential schistosomula-killing and anti-liver-fibrosis agents in the future.