Basic Research
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Apr 28, 2007; 13(16): 2289-2297
Published online Apr 28, 2007. doi: 10.3748/wjg.v13.i16.2289
Effect of herbal medicine Juzentaihoto on hepatic and intestinal heat shock gene expression requires intestinal microflora in mouse
Miho Kato, Atsushi Ishige, Naoko Anjiki, Masahiro Yamamoto, Yoshifumi Irie, Mitsue Taniyama, Ryoko Kibe, Junichiro Oka, Yoshimi Benno, Kenji Watanabe
Miho Kato, Atsushi Ishige, Naoko Anjiki, Masahiro Yamamoto, Yoshifumi Irie, Kenji Watanabe, Department of Kampo Medicine, Keio University, School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan
Miho Kato, Junichiro Oka, Faculty of Pharmaceutical Science, Tokyo University of Science, 264 Yamazaki, Noda City, Chiba 278-8519, Japan
Miho Kato, Ryoko Kibe, Yoshimi Benno, Japan Collection of Microorganisms, Riken, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan
Masahiro Yamamoto, Mitsue Taniyama, Pharmacology Research Department, Tsumura Research Institute, Research Division, 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan
Author contributions: All authors contributed equally to the work.
Supported by a Special Coordination Funds for Promoting Science and Technology by Ministry of Education, Culture, Sports, Science and Technology (MEXT); and a Grant-in-Aid for Exploratory Research by MEXT
Correspondence to: Kenji Watanabe, Department of Kampo Medicine, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan. toyokeio@sc.itc.keio.ac.jp
Telephone: +81-3-53663824 Fax: +81-3-53663825
Received: January 16, 2007
Revised: January 29, 2007
Accepted: February 8, 2007
Published online: April 28, 2007
Abstract

AIM: To evaluate the role of intestinal microflora in the effects of multi-herbal medicine on gene expression in the gut and liver.

METHODS: The multi-herbal medicine Juzentaihoto (JTX) was administered to five germ-free mice and regular mice for 2 wk. Among the results of the comprehensive gene chip analysis of the intestine and liver, we featured heat shock proteins (HSPs) 70 and 105 because their gene expression changed only in the presence of microflora. Real-time RT-PCR was performed to confirm the expression levels of these HSP genes. To determine whether JTX acts directly on the HSP genes, sodium arsenite (SA) was used to induce the heat shock proteins directly. To examine the change of the intestinal microflora with administration of JTX, the terminal restriction fragment polymorphism (T-RFLP) method was used. To identify the changed bacteria, DNA sequencing was performed.

RESULTS: Heat shock protein gene expression, documented by gene chip and real-time RT-PCR, changed with the administration of JTX in the regular mice but not in the germ-free mice. JTX did not suppress the direct induction of the HSPs by SA. T-RFLP suggested that JTX decreased unculturable bacteria and increased Lactobacillus johnsoni. These data suggested that JTX changed the intestinal microflora which, in turn, changed HSP gene expression.

CONCLUSION: Intestinal microflora affects multi-herbal product JTX on the gene expression in the gut and liver.

Keywords: Herbal medicine; Juzentaihoto; Intestinal microflora; Terminal restriction fragment length polymorphism; Heat shock protein