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


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.



bovine serum albumin


ethylenediaminetetraacetic acid


Gynostemma pentaphyllum


gypenoside XLIX


human embryonic kidney 293


human umbilical vein endothelial cells


inducible nitric oxide synthase






nuclear factor-kappaB


nitric oxide


phosphate-buffered saline


pyrrolidine dithiocarbamate


peroxisome proliferator-activated receptor


reverse transcription polymerase chain reaction


sodium dodecyl sulfate


tumor necrosis factor-α


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The authors wish to thank Ankang Pharmaceutical Company Beijing, China, for its generous gift of gypenosides extract, and Dr Rujee K. Duke and Mr Bruce N. Tattam for their assistance in the project.

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Correspondence to Basil D. Roufogalis.

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Tom Hsun-Wei Huang and Yuhao Li contributed equally.

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Huang, T.H., Li, Y., Razmovski-Naumovski, V. et al. Gypenoside XLIX isolated from Gynostemma pentaphyllum inhibits nuclear factor-kappaB activation via a PPAR-alpha-dependent pathway. J Biomed Sci 13, 535–548 (2006).

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Key words

  • Gynostemma pentaphyllum
  • gypenoside
  • nuclear factor-kappaB
  • peroxisome proliferator-activated receptor-alpha