Different Effects Of Four Ingredients Of Danshen On The CYP3A4 And CYP2C9 Expressions

Objective Danshen, the dried root and rhizome of Salvia miltiorrhiza Bunge,is composed by lipophilic ingredients and water-soluble ingredients. Cryptotanshinone and tanshinone I are the lipophilic ingredients of Danshen. Protocatechuic aldehyde and danshensu are the water-soluble ingredients of Danshen. Effects of cryptotanshinone, tanshinone I, protocatechuic aldehyde and danshensu are investigated in Chang liver cells. Confirming the effect on cytochrome P450 enzyme and analyzing the drug-drug interaction could make for medicine administrated rationally.Methods CCK-8 assay was performed to determine the proliferation of Chang liver cells after treating with cryptotanshinone, tanshinone I, protocatechuic aldehyde and danshensu. Quantificational reverse transcription polymerase chain reaction and Western blotting were performed to exam the expression of CYP3A4 and CYP2C9 protein and m RNA respectively.Results Cryptotanshinone significantly inhibited the m RNA and protein expression of CYP3A4(p<0.05), but had no effect on the m RNA and protein expression of CYP2C9. The expression of CYP3A4 m RNA expression was inhibited by treating with 10?M tanshinone I,which had no effect on the CYP3A4 protein expression. The expression of CYP3A4 m RNA and protein expression was inhibited by administrating 100?M tanshinone I(p<0.05). Tanshinone I did not significantly effect on the m RNA and protein expression of CYP2C9. 10?M protocatechuic aldehyde had no effect on the m RNA and protein expression of CYP3A4, however, 100 ?M protocatechuic aldehyde inhibited the protein and m RNA expression of CYP3A4(p<0.05). 10?M protocatechuic aldehyde had no effect on the m RNA and protein expression of CYP2C9. 100?M protocatechuic aldehyde inhibited the expression of CYP3A4 m RNA(p<0.05) but not protein. The expression of CYP3A4 m RNA but not protein expression was inhibited by administrating 10?M danshensu in 7 days(p<0.05). The expression of CYP3A4 m RNA and protein expression was inhibited by administrating 100?M danshensu(p<0.05). 10?M and 100?M danshensu inhibited the m RNA expression of CYP2C9(p<0.05), but had no significantly effect on the protein expressionConclusion Crypotanshinone, tanshinone I, protocatechuic aldehyde and danshensu could inhibit the protein and m RNA expression of CYP3A4. Crypotanshinone, tanshinone I, protocatechuic aldehyde had no effect on protein and m RNA expression of CYP2C9. Danshensu could inhibit the m RNA expression of CYP2C9 but not effect on the protein expression. These results indicate that danshen colud inhibit CYP3A4 expression, which would effect on the metabolism of the substate of CYP3A4. High dosage and continual administrating medicines should be notice about the drug-drug interaction.