Molecular mechanisms of therapeutic effects of Saiko-keishi-to on spontaneous chronic pancreatitis in the WBN/Kob rat :

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  • MOTOO,Yoshiharu
    Department of Internal Medicine and Medical Oncology, Cancer Research Institute, Kanazawa University
  • XIE,Min-Jue
    Department of Internal Medicine and Medical Oncology, Cancer Research Institute, Kanazawa University
  • SU,Shi-Bing
    Department of Internal Medicine and Medical Oncology, Cancer Research Institute, Kanazawa University
  • SAWABU,Norio
    Department of Internal Medicine and Medical Oncology, Cancer Research Institute, Kanazawa University

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Abstract

Saiko-keishi-to (TJ-10) has been clinically used as an oral therapeutic drug for chronic pancreatitis. In this review, we present our data on molecular action mechanisms of TJ-10 on spontaneous chronic pancreatitis in the WBN/Kob rats. Anti-inflammatory effects of TJ-10 were suggested by the suppression of the gene expressions of pancreatitis-associated protein (PAP), cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-6 by reverse transcription-polymerase chain reaction (RT-PCR) analysis. Anti-fibrotic effects were confirmed by the observations on the amelioration of pancreatic fibrosis assessed with AZAN staining and the analysis of expressions of fibrosis-related factors such as transforming growth factor (TGF)-β, α-smooth muscle actin, type III collagen and fibronectin. Anti-apoptotic effect was examined with the TUNEL method and the analysis of apoptosis-related factors such as Fas and Fas ligand. Anti-oxidant effect was suggested by the findings of TJ-10-induced enhancement of the expression of superoxide dismutase and the suppression of the expression of inducible nitric oxide synthase. These results suggest that TJ-10 is effective for chronic pancreatitis by the major four action mechanisms: anti-inflammatory, anti-fibrotic, anti-apoptotic, and anti-oxidant effects.

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