Effects of Andrographis paniculata extract and Andrographolide on hepatic cytochrome P450 mRNA expression and monooxygenase activities after in vivo administration to rats and in vitro in rat and human hepatocyte cultures.
The expression of cytochrome P450 (CYP) is regulated by both endogenous factors and foreign compounds including drugs and natural compounds such as herbs. When herbs are co-administrated with a given drug in modern medicine it can lead to drug-herb interaction that can be clinically significant. The ability of Andrographis paniculata extract (APE) and Andrographolide (AND), the most medicinally active phytochemical in the extract, to modulate hepatic CYP expression was examined in vivo in rats and in vitro in rat and human hepatocyte cultures. After in vivo administration, APE at dose levels of 0.5 g/kg/day (i.e. 5 mg/kg/day AND equivalents) and at 2.5 g/kg/day (i.e. 25 mg/kg/day AND equivalents) and AND at dose levels of 5 and 25 mg/kg/day significantly decreased CYP2C11 activity. In primary cultures of rat and human hepatocytes, treatment with AND 50 microM and APE-containing 50 microM AND also resulted in significant decreases in CYP2C expression and activity. In addition, in human hepatocytes, treatment with APE and AND 50 microM resulted in a decrease in CYP3A expression and activity. In conclusion, this study suggests that AND and APE could cause herb-drug interactions in humans through modulation of CYP2C9 and CYP3A4 expression and activities.
Pekthong
Dumrongsak
D
Laboratoire de Toxicologie Cellulaire, EA 4267, IFR 133, UFR Pharmacie, Place Saint-Jacques, 25030 Besançon, France.
Blanchard
Nadège
N
Abadie
Catherine
C
Bonet
Alexandre
A
Heyd
Bruno
B
Mantion
Georges
G
Berthelot
Alain
A
Richert
Lysiane
L
Martin
Hélène
H
D000284:Administration, Oral; D000368:Aged; D035685:Andrographis / Q000737:chemistry*; D000818:Animals; D002478:Cells, Cultured; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008099:Liver / Q000201:enzymology; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
D065607:Cytochrome P-450 Enzyme Inhibitors; D004224:Diterpenes; D010936:Plant Extracts; D012333:RNA, Messenger; C030419:andrographolide; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases