Journal of
Medicinal Plants Research

  • Abbreviation: J. Med. Plants Res.
  • Language: English
  • ISSN: 1996-0875
  • DOI: 10.5897/JMPR
  • Start Year: 2007
  • Published Articles: 3812

Full Length Research Paper

Inhibitory effect of caffeic acid and its derivatives on human liver cytochrome P450 3A4 activity

Churdsak Jaikang1, Kanokporn Niwatananun2, Paitoon Narongchai3, Siripun Narongchai3 and Chaiyavat Chaiyasut1*
1Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai - 50200, Thailand. 2Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai-50200, Thailand. 3Department of Forensic Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai - 50200, Thailand.
Email: [email protected]

  •  Accepted: 27 April 2011
  •  Published: 04 August 2011


Effects of caffeic acid (CAF) and its derivatives on human liver CYP3A4 activity were evaluated by using diazepam as a substrate. It was found that CAF inhibited CYP3A4 activity by uncompetitive inhibition with IC50 0.72 µM, whereas ester and amide analogues inhibited CYP3A4 by competitive inhibition with IC50 value of 0.31, 0.37, 0.46, 0.49, 0.53, 0.58, 0.75 and 0.82 µM for ethyl 1- (3’,4’-dihydroxyphenyl) propen amide (EDPA), phenmethyl 1- (3’,4’-dihydroxyphenyl) propen amide (PMDPA), phenethyl 1- (3’,4’-dihydroxyphenyl) propen amide (PEDPA), phenylethyl 1- (3’,4’-dihydroxyphenyl) propenate (PC), ethyl 1- (3’,4’-dihydroxyphenyl) propenate (EC), octyl 1- (3’,4’-dihydroxyphenyl) propen amide (ODPA), octyl 1- (3’,4’-dihydroxyphenyl) propenate (OC) and phenylmethyl 1- (3’,4’-dihydroxyphenyl) propenate (BC), respectively. The Kvalues of CAF, PMDPA, EC, PC, ODPA, PEDPA, OC, EDPA and BC were 0.24, 0.29, 0.49, 0.56, 0.57, 0.59, 0.62, 0.62 and 1.03 µM, respectively. However, CAF and its derivatives had high potential to inhibit CYP3A4. Therefore, consumption of herbal medicine containing CAF and its derivatives that are concomitant with other medications should be cautiously monitored.


Key words: Cytochrome P450 3A4, caffeic acid, caffeic acid amide, caffeic acid ester.


EDPA, Ethyl 1- (3’, 4’-dihydroxyphenyl) propenamide; ODPA,  octyl 1- (3’, 4’-dihydroxyphenyl) propen amide; PMDPA,  phenmethyl 1- (3’, 4’-dihydroxyphenyl) propen amide; PEDPA,  phenethly 1- (3’, 4’-dihydroxyphenyl) propen amide; EC,  ethyl 1-(3’,4’-dihydroxyphenyl) propenate; OC, octyl 1- (3’,4’-dihydroxyphenyl) propenate; BC,phenylmethyl 1-(3’,4’-dihydroxyphenyl) propenate; PC, phenylethyl 1- (3’,4’-dihydroxyphenyl) propenate; CAF, caffeic acid; CYP, cytochrome P450.