Gypenoside XLIX isolated from Gynostemma pentaphyllum inhibits nuclear factor-kappaB activation via a PPAR-alpha-dependent pathway
- 10 March 2006
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Biomedical Science
- Vol. 13 (4), 535-548
- https://doi.org/10.1007/s11373-006-9076-8
Abstract
Nuclear factor (NF)-κB is important in the generation of inflammation. Besides regulating lipid metabolism, peroxisome proliferator-activated receptor (PPAR)-α activators also reduce NF-κB activation to terminate activation of inflammatory pathways. Gynostemma pentaphyllum (GP) has been used to treat various inflammatory diseases and hyperlipidemia. Here, we demonstrate that GP extract and one of its main components, Gypenoside XLIX (Gyp-XLIX) inhibited LPS-induced NF-κB activation in murine macrophages. Furthermore, Gyp-XLIX restored the LPS- and TNF-α-induced decrease in cytosolic I-κBα protein expression and inhibited the translocation of NF-κB(p65) to the nucleus in THP-1 monocyte and HUVEC cells. The inhibition of LPS- and TNF-α-induced NF-κB luciferase activity in macrophages was abolished by MK-886, a selective PPAR-α antagonist. GP extract and Gyp-XLIX (EC50: 10.1 μM) enhanced PPAR-α luciferase activity in HEK293 cells transfected with the tK-PPREx3-Luc reporter plasmid and expression vectors for PPAR-α. Additionally, Gyp-XLIX specifically enhanced PPAR-α mRNA and protein expression in THP-1-derived macrophage cells. The selectivity of Gyp-XLIX for PPAR-α was demonstrated by the activation of only PPAR-α in HEK293 cells transfected with expression vectors for PPAR-α, PPAR-β/δ or PPAR-γ1 plasmids and in THP-1-derived macrophage naturally expressing all three PPAR isoforms. The present study demonstrates that Gyp-XLIX, a naturally occurring gynosaponin, inhibits NF-κB activation via a PPAR-α-dependent pathway.Keywords
This publication has 45 references indexed in Scilit:
- Cardiovascular Drugs Inhibit MMP-9 Activity from Human THP-1 MacrophagesDNA and Cell Biology, 2004
- Expression of adiponectin receptors in human macrophages and regulation by agonists of the nuclear receptors PPARα, PPARγ, and LXRBiochemical and Biophysical Research Communications, 2003
- Gypenosides derived from Gynostemma pentaphyllum suppress NO synthesis in murine macrophages by inhibiting iNOS enzymatic activity and attenuating NF-κB-mediated iNOS protein expressionNitric Oxide, 2003
- Fibrates down-regulate IL-1–stimulated C-reactive protein gene expression in hepatocytes by reducing nuclear p50-NFκB–C/EBP-β complex formationBlood, 2003
- Inhibition of peroxisome-proliferator-activated receptor (PPAR)α by MK886Biochemical Journal, 2001
- Expression of Peroxisome Proliferator-Activated Receptor α (PPARα) in Primary Cultures of Human Vascular Endothelial CellsBiochemical and Biophysical Research Communications, 1998
- Structure, Regulation and Function of NF-kappaBAnnual Review of Cell Biology, 1994
- Protection of vascular endothelial cells from hydrogen peroxide-induced oxidant injury by gypenosides, saponins ofGynostemma pentaphyllumPhytotherapy Research, 1993
- Dammarane saponins of Gynostemna pentaphyllum Makino and isolation of malonylginsenosides-Rb1, -Rd, and malonylgypenoside V.CHEMICAL & PHARMACEUTICAL BULLETIN, 1989
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976