Gene expression profiling predicts liver responses to a herbal remedy after partial hepatectomy in mice.
The aim of this study was to demonstrate that regenerating liver responses to a herbal remedy could be presented by gene expression profiling. Compositions of the ingredients in the remedy containing Scutellaria baicalensis Georgi and Bupleurum scorzonerifolfium Wild (S/B remedy) were analyzed and quantified by high performance liquid chromatography. By using a 70% partial hepatectomy in BALB/c mice as an in vivo model, the effects of high dose (50 mg/kg) and low dose (1 mg/kg) S/B remedy were evaluated by cDNA microarray, followed by RT-PCR and real-time PCR confirmation. Factors affecting proliferative activities of mouse hepatocytes were measured by DNA flow cytometry, BrdU incorporation assay and serum interleukin-6 (IL-6) level. Based on global gene expression profiles, the results showed that the low dose S/B remedy down-regulated expression of immediate early genes and cell cycle-related genes, whereas the high dose had opposite effects. The gene expression was further verified by real-time RT-PCR. Proliferative activities, in terms of synthetic phase fractions and G2/M phase fractions, in vehicle, low dose, and high dose groups were 18.45+/-2.56%, 14.65+/-1.06%; 9.27+/-0.85%, 7.80+/-0.11%; and 18.90+/-2.17%, 22.95+/-0.25%, respectively. The serum IL-6 level was also dose-dependent in both low and high dose S/B remedy-treated mice. We conclude that in vivo gene expression profiling correlates with liver responses to a herbal remedy, which provides a new direction for pharmaceutical studies on human diseases.
Wang
Jir-You
JY
Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, 155, Sec. 2, Li-Nong Street, Peitou, Taipei, 112 Taiwan, R.O.C.
Chiu
Jen-Hwey
JH
Tsai
Tung-Hu
TH
Tsou
Ann-Ping
AP
Hu
Cheng-Po
CP
Chi
Chin-Wen
CW
Yeh
Shou-Fan
SF
Lui
Wing-Yiu
WY
Wu
Chew-Wun
CW
Chou
Chen-Kung
CK
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D029972:Bupleurum / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000032:analysis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006498:Hepatectomy / Q000379:methods; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000601:surgery; D008115:Liver Regeneration / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010936:Plant Extracts / Q000032:analysis / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D031364:Scutellaria baicalensis / Q000737:chemistry; D013997:Time Factors
D015850:Interleukin-6; D010936:Plant Extracts; D004247:DNA; D001973:Bromodeoxyuridine