PMID- 37049902
OWN - NLM
STAT- MEDLINE
DCOM- 20230414
LR  - 20230415
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 28
IP  - 7
DP  - 2023 Mar 31
TI  - Modulatory Effects of Atractylodin and beta-Eudesmol on Human Cytochrome P450 
      Enzymes: Potential Drug-Drug Interactions.
LID - 10.3390/molecules28073140 [doi]
LID - 3140
AB  - Atractylodin and beta-eudesmol, the major bioactive compounds in Atractylodes 
      lancea, are promising candidates for anti-cholangiocarcinoma. The inhibitory 
      effects of both compounds on human rCYP1A2, rCYP2C9, rCYP2C19, rCYP2D6 and 
      rCYP3A4 enzymes were investigated using luminogenic CYP450 kits. The modulatory 
      effects were investigated in mouse livers following a daily oral dose of 
      atractylodin or beta-eudesmol at 100 mg/kg body weight for 1, 7, 14, and 21 days. 
      The inhibitory effects of both compounds on all rCYP450s were weak (IC(50): 167 
      to >686 microM). beta-Eudesmol showed the most potent inhibitory effect on rCYP2C19 
      (IC(50) = 172.7 microM) and rCYP3A4 (IC(50) = 218.6 microM). Results of the ex vivo study 
      showed that short exposure (1-7 days) of atractylodin and beta-eudesmol resulted in 
      the upregulation of mRNA. Prolonged exposure to the daily oral dose for at least 
      14 days significantly downregulated the expressions of mRNA and proteins, which 
      correlated with the decrease in the activities of mCYP1A2 and mCYP3A11. Based on 
      the results of the ex vivo study, clinical uses of atractylodin or beta-eudesmol for 
      the treatment of cholangiocarcinoma are of concern for the risk of toxicity due 
      to hCYP3A4 inhibition following chronic dosing, as well as the metabolic 
      interaction with the coadministered drugs that are metabolized by hCYP3A4.
FAU - Thiengsusuk, Artitaya
AU  - Thiengsusuk A
AD  - Graduate Studies, Chulabhorn International College of Medicine, Thammasat 
      University, Pathumthani 12120, Thailand.
FAU - Plengsuriyakarn, Tullayakorn
AU  - Plengsuriyakarn T
AD  - Graduate Studies, Chulabhorn International College of Medicine, Thammasat 
      University, Pathumthani 12120, Thailand.
AD  - Center of Excellence in Pharmacology and Molecular Biology of Malaria and 
      Cholangiocarcinoma, Thammasat University, Pathumthani 12120, Thailand.
FAU - Na-Bangchang, Kesara
AU  - Na-Bangchang K
AD  - Graduate Studies, Chulabhorn International College of Medicine, Thammasat 
      University, Pathumthani 12120, Thailand.
AD  - Center of Excellence in Pharmacology and Molecular Biology of Malaria and 
      Cholangiocarcinoma, Thammasat University, Pathumthani 12120, Thailand.
AD  - Drug Discovery and Development Center, Office of Advanced Science and Technology, 
      Thammasat University, Pathumthani 12120, Thailand.
LA  - eng
GR  - 820/2563/National Research Council of Thailand/
PT  - Journal Article
DEP - 20230331
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 473-15-4 (beta-eudesmol)
RN  - 55290-63-6 (atractylodin)
RN  - 0 (Sesquiterpenes, Eudesmane)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Humans
MH  - *Sesquiterpenes, Eudesmane/pharmacology
MH  - Cytochrome P-450 Enzyme System
MH  - Drug Interactions
MH  - *Atractylodes/metabolism
PMC - PMC10095747
OTO - NOTNLM
OT  - atractylodin
OT  - metabolic drug interaction
OT  - beta-eudesmol
COIS- The authors declare no conflict of interest.
EDAT- 2023/04/14 06:00
MHDA- 2023/04/14 06:41
PMCR- 2023/03/31
CRDT- 2023/04/13 01:27
PHST- 2023/03/13 00:00 [received]
PHST- 2023/03/26 00:00 [revised]
PHST- 2023/03/28 00:00 [accepted]
PHST- 2023/04/14 06:41 [medline]
PHST- 2023/04/13 01:27 [entrez]
PHST- 2023/04/14 06:00 [pubmed]
PHST- 2023/03/31 00:00 [pmc-release]
AID - molecules28073140 [pii]
AID - molecules-28-03140 [pii]
AID - 10.3390/molecules28073140 [doi]
PST - epublish
SO  - Molecules. 2023 Mar 31;28(7):3140. doi: 10.3390/molecules28073140.