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Nuciferine downregulates Per-Arnt-Sim kinase expression during its alleviation of
lipogenesis and inflammation on oleic acid-induced hepatic steatosis in HepG2
cells
#MMPMID26539118
Zhang DD
; Zhang JG
; Wu X
; Liu Y
; Gu SY
; Zhu GH
; Wang YZ
; Liu GL
; Li XY
Front Pharmacol
2015[]; 6
(?): 238
PMID26539118
show ga
Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disease associated
with lipotoxicity, lipid peroxidation, oxidative stress, and inflammation.
Nuciferine, an active ingredient extracted from the natural lotus leaf, has been
reported to be effective for the prevention and treatment of NAFLD. Per-Arnt-Sim
kinase (PASK) is a nutrient responsive protein kinase that regulates lipid and
glucose metabolism, mitochondrial respiration, and gene expression. The aim of
the present study was to investigate the protective effect of nuciferine against
NAFLD and its inhibitory effect on PASK, exploring the possible underlying
mechanism of nuciferine-mediated inhibition on NAFLD. Relevant biochemical
parameters (lipid accumulation, extent of oxidative stress and release of
inflammation cytokines) in oleic acid (OA)-induced HepG2 cells that mimicked
steatosis in vitro were measured and compared with the control. It was found that
nuciferine and silenced-PASK (siRNA PASK) both inhibited triglyceride (TG)
accumulation and was effective in decreasing fatty acid (FFAs). The content of
total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) were increased
respectively by nuciferine and siRNA PASK without increase in glutathione (GSH).
Malondialdehyde (MDA) was decreased respectively by nuciferine and siRNA PASK. In
addition, nuciferine decreased TNF-a, IL-6 and IL-8 as well as the siRNA PASK
group. IL-10 was increased by nuciferine and siRNA PASK respectively. Further
investigation revealed that nuciferine and siRNA PASK could respectively regulate
the expression of target genes involved in lipogenesis and inflammation,
suggesting that nuciferine may be a potential therapeutic treatment for NAFLD.
Furthermore, the modulated effect of nuciferine on (OA)-induced HepG2 cells
lipogenesis and inflammation, which was accompanied with PASK inhibition, was
also consistent with siRNA PASK, implying that PASK might play a role in
nuciferine-mediated regulation on NAFLD.
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