Soluble Epoxide Hydrolase Inhibitory Activity of Selaginellin Derivatives from Selaginella tamariscina

Abstract

Selaginellin derivatives 1-3 isolated from Selaginella tamariscina were evaluated for their inhibition of soluble epoxide hydrolase (sEH) to demonstrate their potential for the treatment of cardiovascular disease. All selaginellin derivatives (1-3) inhibited sEH enzymatic activity and PHOME hydrolysis, in a dose-dependent manner, with IC50 values of 3.1 ± 0.1, 8.2 ± 2.2, and 4.2 ± 0.2 μM, respectively. We further determined that the derivatives function as non-competitive inhibitors. Moreover, the predicted that binding sites and interaction between 1-3 and sEH were solved by docking simulations. According to quantitative analysis, 1-3 were confirmed to have high content in the roots of S. tamariscina; among them, selaginellin 3 exhibited the highest content of 189.3 ± 0.0 μg/g.

Keywords: Selaginella tamariscina; Selaginellaceae; non-competitive inhibition; selaginellin; soluble epoxide hydrolase.

Figure 1

Structures of selaginellin derivatives from S. tamariscina.

Figure 2

Effects of selaginellin derivatives 1–3 on the sEH activity (A); Lineweaver-Burk plots of sEH inhibition by 1–3 on the hydrolytic activity of sEH (B–D); and Secondary re-plot of Slope vs. [I] (E).

Figure 3

Binding pose at the lowest energy between compounds 1–3 and free enzyme (A–C); binding pose at the lowest energy between compounds for 1–3 and enzyme-substrate complex (D–F).

Figure 3

Binding pose at the lowest energy between compounds 1–3 and free enzyme (A–C); binding pose at the lowest energy between compounds for 1–3 and enzyme-substrate complex (D–F).

Figure 4

Pattern analysis of selaginellin A (1), selaginellin B (2), and selaginellin (3) in methanol extracts (0.5 mg/mL) from the S. tamariscina whole plants and roots.