<I>In vitro</I> Peroxisome Proliferator-Activated Receptors α and γ Ativation Effects of Iridoids and Lignans Isolated from the Leaves of <I>Nephrolepis exaltata</I> L. (Nephrolepidaceae)

Abstract

Peroxisome proliferator-activated receptor-γ (PPARγ) is the drug target for certain antidiabetic agents. While peroxisome proliferator-activated receptor-α (PPARα) is targeted by lipid lowering agents. Compounds with double activation on PPARα/γ are major components in prevention of progression of renal damage. The aim of the study is to evaluate the in vitro PPARα/γ activation effects of iridoids and lignans isolated from the leaves of Nephrolepis exaltata L. (Nephrolepidaceae). Phytochemical investigation of the ethanol extract of Nephrolepis exaltata resulted in the isolation of megastigmens, lignans and iridoids and their structures elucidated. The effect of the isolated compounds on PPAR-α and PPAR-γ in human hepatoma (HepG2) cells were investigated via reporter gene assays using a 96-well tissue culture plate were transfected with cells at a density of 5 × 104 cells/well and grown for 24 h. Each cell were treated with plant extract (25, 50 and 100 μg/mL), the isolated compounds, ciprofibrate (10 µM) for PPARα or rosiglitazone (10 µM) for PPARγ assay. The luciferase activity was measured using a luciferase assay system. Compounds isolated from the leaves of N. exaltata dehydrovomifoliol (1), Dehydrololiolide (2), methoxygaertneroside (3), pinoresinol 4′-O-β-D-glucopyranoside (4) glochidiobioside (5), have double activities on PPARα/γ with a fold induction of more than 2.0 over the control. The compounds were non-cytotoxic to HepG2 cells as the cell viability for all the compound remained greater than 80%. Compounds isolated from the leaves of ethanol extract of N. exaltata has dual PPARα and γ indicating their potential to maintain the integrity of the kidney.