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Japanese Kampo Saireito Has a Liver‐Protective Effect Through the Inhibition of Inducible Nitric Oxide Synthase Induction in Primary Cultured Rat Hepatocytes
Author(s) -
Miki Hirokazu,
Tokuhara Katsuji,
Oishi Masaharu,
Nakatake Richi,
Tanaka Yoshito,
Kaibori Masaki,
Nishizawa Mikio,
Okumura Tadayoshi,
Kon Masanori
Publication year - 2016
Publication title -
journal of parenteral and enteral nutrition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.935
H-Index - 98
eISSN - 1941-2444
pISSN - 0148-6071
DOI - 10.1177/0148607115575035
Subject(s) - nitric oxide synthase , nitric oxide , proinflammatory cytokine , kampo , liver injury , tumor necrosis factor alpha , pharmacology , medicine , inflammation , biology , chemistry , pathology , alternative medicine
Background: Japanese herbal medicine, Kampo saireito, is used for treatments in patients with digestive diseases, including chronic hepatitis and cirrhosis. However, few studies demonstrate scientific evidence for liver‐protective effects of saireito. In inflamed liver, proinflammatory cytokines such as tumor necrosis factor (TNF)–α and interleukin (IL)–1β stimulate the induction of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production. Excessive levels of NO synthesized by iNOS have been implicated as one of the factors in liver injury, so it is essential to reduce the induction of iNOS for the prevention of liver injury. In this study, we examined IL‐1β–stimulated hepatocytes as a simple “in vitro injury model” to investigate liver‐protective effects of saireito. Method: Primary cultured rat hepatocytes were treated with IL‐1β in the presence or absence of saireito. The induction of NO production and iNOS and its signaling pathway were analyzed. Results: Saireito inhibited the production of NO dose and time dependently and reduced the expression of iNOS messenger RNA (mRNA) and its protein. Saireito had no effect on IκB degradation but inhibited the translocation of nuclear factor (NF)–κB to the nucleus and its DNA binding. Saireito also inhibited the activation of Akt, resulting in the reduction of type I IL‐1 receptor (IL‐1RI) mRNA and protein expression. Conclusion: These findings demonstrate that saireito suppresses iNOS gene expression through the inhibition of NF‐κB and IL‐1RI–dependent pathways, leading to the reduction of NO production. Saireito may have therapeutic potential for organ injuries, including liver.