Japanese Herbal Medicine Hochuekkito Inhibits the Expression of Proinflammatory Biomarker, Inducible Nitric Oxide Synthase, in HepatocytesMiho Matsumiya1, Masaki Kaibori1, Yoshiro Araki1, Takashi Matsuura1, Masaharu Oishi1, Yoshito Tanaka1, Mikio Nishizawa2, Tadayoshi Okumura1,3* and A-Hon Kwon1
- *Corresponding Author:
- Dr. Tadayoshi Okumura, Ph.D.
Department of Surgery
Kansai Medical University, 10-15 Fumizonocho
Moriguchi, Osaka 570-8506, Japan
Tel: +81- 6-6993-9474
E-mail: [email protected]
Received date: March 05, 2012; Accepted date: March 26, 2012; Published date: March 27, 2012
Citation: Matsumiya M, Kaibori M, Araki Y, Matsuura T, Oishi M, et al. (2012) Japanese Herbal Medicine Hochuekkito Inhibits the Expression of Proinflammatory Biomarker, Inducible Nitric Oxide Synthase, in Hepatocytes. Medchem 2:112. doi:10.4172/2161-0444.1000112
Copyright: © 2012 Matsumiya M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Hochuekkito (TJ-41) is used for the treatment of complaints in patients with general fatigue. However, there is little scientific evidence to demonstrate the liver-protective effects of TJ-41. In the inflamed liver, proinflammatory cytokines stimulate the induction of inducible nitric oxide synthase (iNOS). Over-production of NO by iNOS has been implicated as a factor in liver injury. We examined proinflammatory cytokine-stimulated hepatocytes as a simple in vitro injury model to determine liver-protective effects of TJ-41. The objective was to investigate whether TJ-41 influences iNOS induction and to determine its mechanism. Primary cultured rat hepatocytes were treated with interleukin (IL)-1β in the presence or absence of TJ-41. The induction of iNOS and its signaling pathway were analyzed. IL-1β produced increased levels of NO. This effect was inhibited by TJ-41, which exerted its maximal effects at 6 mg/ml. TJ-41 decreased the levels of iNOS protein and its mRNA expression. Experiments with nuclear extracts revealed that TJ- 41 inhibited the translocation of NF-κB to the nucleus and its DNA binding. TJ-41 also inhibited the activation of Akt, resulting in the reduction of type I IL-1 receptor mRNA and protein expression. Transfection experiments demonstrated that TJ-41 suppressed iNOS induction by the inhibition of promoter transactivation and mRNA stabilization. TJ-41 reduced the expression of an iNOS gene antisense-transcript, which is involved in iNOS mRNA stability. Results indicate that TJ-41 inhibits the induction of iNOS at both transcriptional and post-transcriptional steps, leading to the prevention of NO production. TJ-41 may have therapeutic potential for various liver injuries through the suppression of iNOS induction.