curcumin and 5-hydroxy-6-8-11-14-eicosatetraenoic-acid

Curcumin exhibits significant antitumorigenic activity in various preclinical models; data supporting its chemopreventive activity in humans, however, are lacking. To our knowledge, the first published results of a phase II chemoprevention study of curcumin are reported in this issue of the journal by Carroll and colleagues (beginning on page 354), who examined the effects of oral curcumin on various putative biomarkers of colonic tumorigenesis in smokers. This perspective discusses the potential significance and limitations of the current study findings in addressing the question of whether curcumin is clinically active as a chemopreventive agent.

Topics: Anticarcinogenic Agents; Apoptosis; Biological Availability; Biomarkers, Tumor; Chemoprevention; Clinical Trials as Topic; Curcumin; Dinoprostone; Humans; Hydroxyeicosatetraenoic Acids; Neoplasms; Research Design; Smoking; Treatment Outcome

A wide variety of phenolic compounds and flavonoids present in spices possess potent antioxidant, antimutagenic and anticarcinogenic activities. We examined whether 5-lipoxygenase (5-LO), the key enzyme involved in biosynthesis of leukotrienes is a possible target for the spices. Effect of aqueous extracts of turmeric, cloves, pepper, chili, cinnamon, onion and also their respective active principles viz., curcumin, eugenol, piperine, capsaicin, cinnamaldehyde, quercetin, and allyl sulfide were tested on human PMNL 5-LO activity by spectrophotomeric and HPLC methods. The formation of 5-LO product 5-HETE was significantly inhibited in a concentration-dependent manner with IC(50) values of 0.122-1.44 mg for aqueous extracts of spices and 25-83 microM for active principles, respectively. The order of inhibitory activity was of quercetin>eugenol>curcumin>cinnamaldehyde>piperine>capsaicin>allyl sulfide. Quercetin, eugenol and curcumin with one or more phenolic ring and methoxy groups in their structure showed high inhibitory effect, while the non-phenolic spice principle allyl sulfide showed least inhibitory effect on 5-LO. The inhibitory effect of quercetin, curcumin and eugenol was similar to that of synthetic 5-LO inhibitors-phenidone and NDGA. Moreover, the inhibitory potency of aqueous extracts of spice correlated with the active principles of their respective spices. The synergistic or antagonistic effect of mixtures of spice active principles and spice extracts were investigated and all the combinations of spice active principles/extracts exerted synergistic effect in inhibiting 5-LO activity. These findings clearly suggest that phenolic compounds present in spices might have physiological role in modulating 5-LO pathway.

Topics: Arachidonate 5-Lipoxygenase; Cell Culture Techniques; Chromatography, High Pressure Liquid; Curcuma; Dose-Response Relationship, Drug; Humans; Hydroxyeicosatetraenoic Acids; Inhibitory Concentration 50; Lipoxygenase Inhibitors; Molecular Structure; Neutrophils; Onions; Phenol; Plant Extracts; Spices

Various diarylheptanoids including curcumin, bis (3,4-dihydroxy-cinnamoyl) methane, and yakuchinones A & B were screened and found to be potent inhibitors of 5-HETE production by intact human neutrophils, with respective IC50 values of 8.0, 4.4, 5.4, and 4.0 microM. These diarylheptanoids were found to be more potent than BW-755C, Phenidone, and AA-861. We have confirmed a previous report that several of these diarylheptanoids inhibit cyclooxygenase. Thus, curcuminoids and yakuchinones are more accurately characterized as dual inhibitors of arachidonic acid metabolism.

Topics: Catechols; Curcumin; Guaiacol; Humans; Hydroxyeicosatetraenoic Acids; In Vitro Techniques; Neutrophils