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Abstract
<p class="first" id="d10454138e86">Osthole, a coumarin derivative, can increase hepatic
peroxisome proliferator-activated
receptor α (PPARα) expression and reduce hepatic steatosis and inflammatory response
in rats with non-alcoholic steatohepatitis (NASH). In this study, a cell model of
NASH was induced with oleic acid (OA)/lipopolysaccharide (LPS) and treated for 36 h
with different osthole concentrations. Results showed that intracellular lipid and
inflammatory cytokine levels gradually decreased after osthole treatment. These effects,
however, were abolished or attenuated after PPARα gene silencing. Accordingly, PPARα
gene silencing reversed the osthole-mediated expressions of proteins involved in lipid
synthesis and fatty acid oxidation. PPARα gene silencing also abrogated the inhibitory
effect of osthole on nuclear factor kappa B p65 protein expression. These findings
demonstrate that osthole activates PPARα signaling pathway to inhibit lipid accumulation
and inflammatory response in OA/LPS-stimulated hepatocytes.
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