Japanese Kampo Medicine, Ninjinyoeito, Inhibits the Induction of iNOS Gene Expression in Proinflammatory Cytokine-Stimulated Hepatocytes.
Loading...
Date
2014-10
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Background: Japanese Kampo medicine, ninjinyoeito (NYT), is used for the treatment of
complaints in patients with general fatigue, anorexia and anemia, and is recently applied
in patients with chronic hepatitis C. However, there is little scientific evidence to
demonstrate the liver-protective effects of NYT. We examined proinflammatory cytokine
stimulated hepatocytes as a simple in vitro liver injury model to determine liver-protective
effects of NYT and to clarify the mechanisms involved in.
Methods: Primary cultured rat hepatocytes were treated with interleukin (IL)-1β in the
presence or absence of NYT. Inflammatory biomarkers including inducible nitric oxide
synthase (iNOS) and tumor necrosis factor (TNF)-α were analyzed.
Results: IL-1β stimulated the induction of iNOS and enhanced the production of NO.
Simultaneous addition of NYT decreased the levels of iNOS protein and its mRNA
expression, resulting in the reduction of NO production. NYT also reduced the expression
of TNF-α mRNA and enhanced the expression of IL-10 mRNA. NYT inhibited two
essential signaling pathways for iNOS induction, the activation of nuclear factor (NF)-κB
and the upregulation of type I IL-1 receptor. Experiments with transfection and iNOS gene
antisense transcript revealed that NYT reduced the levels of iNOS mRNA at both the
promoter activation and mRNA stabilization steps. The delayed administration of NYT
after IL-1β addition also inhibited iNOS induction.
Conclusions: Results demonstrate that NYT can influence the induction of inflammatory
mediators, such as iNOS and TNF-α, in part through the inhibition of NF-κB activation in
hepatocytes. NYT may have therapeutic potential for various acute liver injuries.
Description
Keywords
Inducible nitric oxide synthase, nitric oxide, liver injury, primary cultured hepatocytes, nuclear factor-κB, type I interleukin-1 receptor, tumor necrosis factor-α
Citation
Tanaka Yoshito, Kaibori Masaki, Miki Hirokazu, Oishi Masaharu, Nakatake Richi, Tokuhara Katsuji, Nishizawa Mikio, Okumura Tadayoshi, Kwon A-Hon. Japanese Kampo Medicine, Ninjinyoeito, Inhibits the Induction of iNOS Gene Expression in Proinflammatory Cytokine-Stimulated Hepatocytes. British Journal of Pharmaceutical Research. 2014 Oct; 4(19): 2226-2244.