Effect of herbal medicine Juzentaihoto on hepatic and intestinal heat shock gene expression requires intestinal microflora in mouse.
OBJECTIVE
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.


CONCLUSIONS
Intestinal microflora affects multi-herbal product JTX on the gene expression in the gut and liver.
Kato
Miho
M
Department of Kampo Medicine, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan.
Ishige
Atsushi
A
Anjiki
Naoko
N
Yamamoto
Masahiro
M
Irie
Yoshifumi
Y
Taniyama
Mitsue
M
Kibe
Ryoko
R
Oka
Junichiro
J
Benno
Yoshimi
Y
Watanabe
Kenji
K
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018053:Arsenites / Q000494:pharmacology; D002939:Ciprofloxacin / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D050957:HSP110 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000382:microbiology*; D007778:Lactobacillus / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017670:Sodium Compounds / Q000494:pharmacology
D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D018053:Arsenites; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D050957:HSP110 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C490783:Hsp105 protein, mouse; D012333:RNA, Messenger; D017670:Sodium Compounds; C063587:juzentaihoto; C017947:sodium arsenite; D002939:Ciprofloxacin