Impact of Curcumin on Microsomal Enzyme Activities: Drug Interaction and Chemopreventive Studies

Abstract

: Curcumin, a yellow pigment in Asian spice, is a natural polyphenol component of Curcuma longa rhizome. Curcuminoid components include curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). Previous studies established curcumin as a safe agent based on preclinical and clinical evaluations and curcuminoids have been approved by the US Food and Drug Administration (FDA) as “Generally Recognized as Safe” (GRAS). The present review collects and summarizes clinical and preclinical studies of curcumin interactions, with an emphasis on the effect of curcumin and curcumin analogs on the mRNA and protein levels of microsomal CYP450 enzymes (phase I metabolism) and their interactions with toxicants, drugs and drug probes. The literature search was conducted using keywords in various scientific databases, including Web of Science, Scopus, PubMed, and Google Scholar. Studies concerning the impact of curcumin and curcumin analogs on microsomal enzyme activity are reviewed and include oral, topical, and systemic treatment in humans and experimental animals, as well as studies from in vitro research. When taken together the data identified some inconsistent results between various studies. The findings showed significant inhibition of CYP450 enzymes by curcumin and its analogs. However such effects often differed when curcumin and curcumin analogs were coadministered with toxicant and other drugs and drug probes. We conclude from this review that herb-drug interactions should be considered when curcumin and curcumin analogs are consumed.

Kinetic Characteristics of Curcumin and Germacrone in Rat and Human Liver Microsomes: Involvement of CYP Enzymes

“…In inhibitory experiment with enzyme activity, curcumin inhibited effects on CYP3A4, 1A2, 2E1 and 2C19, with IC 50 of 24.27 μM, 92.60 μM, 172.05 μM and 11.86 μM, and germacrone inhibited effects on the same CYP enzymes, with IC 50 of 3.57 μM, 78.06 μM, 120.35 μM and 17.84 μM, respectively. The results were generally consistent with those reports, which CYP3A4, 1A2 were effected by germacrone [ 24 , 41 ]. This study for curcumin and germacrone on CYP enzyme can enrich their activity and content.…”

Bisdemethoxycurcumin Reduces Methicillin-Resistant Staphylococcus aureus Expression of Virulence-Related Exoproteins and Inhibits the Biofilm Formation

“…According to the above results, we speculated that reducing the expression level of enterotoxin protein by down-regulating related genes was one of the reasons why BDMC could inhibit enterotoxin. In addition, it has been reported that enterotoxins could bind to polyphenols [25], and BDMC is a polyphenolic compound with two phenolic hydroxyl groups. The hydrophobicity and hydrogen bonding property of the phenolic hydroxyl group are believed to be easily combined with proteins and this chemical structure could be the second reason of the enterotoxins inhibition.…”

Therapeutic Effect of Curcumin on Metabolic Diseases: Evidence from Clinical Studies

“…8-hydroxy-2’-deoxyguanosine (8-OHdG), a potential marker of oxidation-related DNA damage, has been shown to be elevated in patients with NAFLD [ 88 ]. In addition, carboxymethyl lysine (CML) is an AGEs produced as a result of enhanced oxidative stress in NAFLD, and the interaction of AGEs with the receptor for advanced glycosylation end products (RAGE) in hepatocytes can worsen oxidative stress [ 89 , 90 ]. A randomized controlled trial by Mirhafez et al showed that giving phospholipid curcumin capsules (250 mg qd) for 8 weeks significantly reduced 8-OHdG and CML levels in patients with NAFLD, suggesting that curcumin may improve oxidative stress in NAFLD [ 61 ].…”