- 作者: Tom Hsun-Wei Huang; Yuhao Li; Valentina Razmovski-Naumovski, Van Hoan Tran, George Qian Li; Colin C. Duke; Basil D. Roufogalis
- 作者服務機構: Pharmaceutical Chemistry Discipline and Herbal Medicines Research and Education Centre, Faculty of Pharmacy, University of Sydney, A15, S322, Sydney, NSW, 2006, Australia
- 中文摘要: --
- 英文摘要: 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-κΒ 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-κΒ activation in murine macrophages. Furthermore, Gyp-XLIX restored the LPS- and TNF-α-induced decrease in cytosolic Ι-κΒα 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-κΒ luciferase activity in macrophages was abolished by MK-886, a selective PPAR-α antagonist. GP extract and Gyp-XLIX (EC50: 10.1 μΜ) 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.
- 中文關鍵字: --
- 英文關鍵字: Gynostemma pentaphyllum, gypenoside, nuclear factor-kappaB, peroxisome proliferator-activated receptor-alpha