Dose escalation of a curcuminoid formulation

Division of Hematology-Oncology, Department of Internal Medicine, University of Michigan, 2150 CCGC, Ann Arbor, MI 48109-0930, USA.
BMC Complementary and Alternative Medicine (Impact Factor: 1.88). 02/2006; 6:10. DOI: 10.1186/1472-6882-6-10
Source: PubMed

ABSTRACT Curcumin is the major yellow pigment extracted from turmeric, a commonly-used spice in India and Southeast Asia that has broad anticarcinogenic and cancer chemopreventive potential. However, few systematic studies of curcumin's pharmacology and toxicology in humans have been performed.
A dose escalation study was conducted to determine the maximum tolerated dose and safety of a single dose of standardized powder extract, uniformly milled curcumin (C3 Complextrade mark, Sabinsa Corporation). Healthy volunteers were administered escalating doses from 500 to 12,000 mg.
Seven of twenty-four subjects (30%) experienced only minimal toxicity that did not appear to be dose-related. No curcumin was detected in the serum of subjects administered 500, 1,000, 2,000, 4,000, 6,000 or 8,000 mg. Low levels of curcumin were detected in two subjects administered 10,000 or 12,000 mg.
The tolerance of curcumin in high single oral doses appears to be excellent. Given that achieving systemic bioavailability of curcumin or its metabolites may not be essential for colorectal cancer chemoprevention, these findings warrant further investigation for its utility as a long-term chemopreventive agent.


Available from: Mack T Ruffin IV, Jun 12, 2015
1 Follower
  • [Show abstract] [Hide abstract]
    ABSTRACT: Forty-three 1,5-diheteroaryl-1,4-pentadien-3-ones were designed as potential curcumin mimics, structurally featuring a central five-carbon dienone linker and two identical nitrogen-containing aromatic rings. They were synthesized using a Horner-Wadsworth-Emmons reaction as the critical step and evaluated for their cytotoxicity and antiproliferative activities towards both androgen-insensitive and androgen-sensitive prostate cancer cell lines, and an aggressive cervical cancer cell line. Most of the synthesized compounds showed distinctly better in vitro potency than curcumin in the four cancer cell lines. The structure-activity data acquired from the study validated (1E,4E)-1,5-dihereroaryl-1,4-pentadien-3-ones as an excellent scaffold for in-depth development for clinical treatment of prostate and cervical cancers. 1-Alkyl-1H-imidazol-2-yl, ortho pyridyl, 1-alkyl-1H-benzo[d]imidazole-2-yl, 4-bromo-1-methyl-1H-pyrazol-3-yl, thiazol-2-yl, and 2-methyl-4-(trifluoromethyl)thiazol-5-yl were identified as optimal heteroaromatic rings for the promising in vitro potency. (1E,4E)-1,5-Bis(2-methyl-4-(trifluoromethyl)thiazol-5-yl)penta-1,4-dien-3-one, featuring with thiazole rings and trifluoromethyl groups, was established as the optimal lead compound due to its good in vitro potency and attractive in vivo pharmacokinetic profiles.
    Journal of Medicinal Chemistry 05/2015; DOI:10.1021/acs.jmedchem.5b00470 · 5.48 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Natural R-(−)-xanthorrhizol possess a number of therapeutic activities including anti-cancer. The pharmacokinetic properties of that poorly aqueous soluble compound could be improved by incorporating it into polymeric materials. Glycerol can produce a functionalized polymer through a polycondensation process. Enzymatic polycondensation of glycerol and divinylesters was studied and xanthorrhizol was covalently loaded via a butanedioate linker to the polymer backbone. It was observed that xanthorrhizol loading to the polymer backbone increases with the increasing of the chain length of a dioate moiety. Enzyme-mediated xanthorrhizol release from a polymer backbone shows that the polymeric prodrug is able to release xanthorrhizol in a sustained manner. Therefore, the approach described here might be valuable for controlled loading and release of such phenolic sesquiterpenes from the polymeric prodrug.
    Journal of Molecular Catalysis B Enzymatic 12/2012; 84:198–204. DOI:10.1016/j.molcatb.2012.05.022 · 2.75 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: For many years now the world's scientific literature has been perfused with articles on the therapeutic potential of natural products, the vast majority of which have herbal origins, as in the case of free radical-induced diseases. What is often overlooked is the effort of researchers who take into consideration the preclinical and clinical evaluation of these herbal products, in order to demonstrate the therapeutic efficacy and safety. The first critical issue to be addressed in the early stages of the preclinical studies is related to pharmacokinetics, which is sometimes not very favorable, of some of these products, which limits the bioavailability after oral intake. In this regard, it is worthy underlining how it is often unethical to propose the therapeutic efficacy of a compound on the basis of preclinical results obtained with far higher concentrations to those which, hopefully, could be achieved in organs and tissues of subjects taking these products by mouth. The most widely used approach to overcome the problem related to the low bioavailability involves the complexation of the active ingredients of herbal products with non-toxic carriers that facilitate the absorption and distribution. Even the induction or inhibition of drug metabolizing enzymes by herbal products, and the consequent variations of plasma concentrations of co-administered drugs, are phenomena to be carefully evaluated as they can give rise to side-effects. This risk is even greater when considering that people lack the perception of the risk arising from an over use of herbal products that, by their very nature, are considered risk-free.
    Frontiers in Pharmacology 04/2015; 6:86. DOI:10.3389/fphar.2015.00086