Journal of Biomedical Science

, Volume 13, Issue 4, pp 535–548

Gypenoside XLIX isolated from Gynostemma pentaphyllum inhibits nuclear factor-kappaB activation via a PPAR-alpha-dependent pathway

Authors

  • Tom Hsun-Wei Huang
    • Pharmaceutical Chemistry Discipline and Herbal Medicines Research and Education Centre, Faculty of PharmacyUniversity of Sydney
  • Yuhao Li
    • Pharmaceutical Chemistry Discipline and Herbal Medicines Research and Education Centre, Faculty of PharmacyUniversity of Sydney
  • Valentina Razmovski-Naumovski
    • Pharmaceutical Chemistry Discipline and Herbal Medicines Research and Education Centre, Faculty of PharmacyUniversity of Sydney
  • Van Hoan Tran
    • Pharmaceutical Chemistry Discipline and Herbal Medicines Research and Education Centre, Faculty of PharmacyUniversity of Sydney
  • George Qian Li
    • Pharmaceutical Chemistry Discipline and Herbal Medicines Research and Education Centre, Faculty of PharmacyUniversity of Sydney
  • Colin C. Duke
    • Pharmaceutical Chemistry Discipline and Herbal Medicines Research and Education Centre, Faculty of PharmacyUniversity of Sydney
    • Pharmaceutical Chemistry Discipline and Herbal Medicines Research and Education Centre, Faculty of PharmacyUniversity of Sydney
Article

DOI: 10.1007/s11373-006-9076-8

Cite this article as:
Huang, T.H., Li, Y., Razmovski-Naumovski, V. et al. J Biomed Sci (2006) 13: 535. doi:10.1007/s11373-006-9076-8

Summary

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.

Key words

Gynostemma pentaphyllumgypenosidenuclear factor-kappaBperoxisome proliferator-activated receptor-alpha

Abbreviations

BSA

bovine serum albumin

EDTA

ethylenediaminetetraacetic acid

GP

Gynostemma pentaphyllum

Gyp-XLIX

gypenoside XLIX

HEK293

human embryonic kidney 293

HUVEC

human umbilical vein endothelial cells

iNOS

inducible nitric oxide synthase

I-κB

inhibitor-κB

LPS

lipopolysaccharide

NF-κB

nuclear factor-kappaB

NO

nitric oxide

PBS

phosphate-buffered saline

PDTC

pyrrolidine dithiocarbamate

PPAR

peroxisome proliferator-activated receptor

RT-PCR

reverse transcription polymerase chain reaction

SDS

sodium dodecyl sulfate

TNF-α

tumor necrosis factor-α

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Copyright information

© National Science Council Taipei 2006