Research Communication Dose-dependent bioavailability indicators for curcumin and two of its novel derivatives Mohamed Abd el Aziz 1 Mohamed El-Asmer 2 Ameen Rezq 1 Abdulrahman Al-Malki 3 Taha Kumosani 3 Hanan Fouad 1 Hanan Ahmed 1 Fatma Taha 1 * Amira Hassouna 1 Hafez Hafez 4 1 Unit of Biochemistry and Molecular Biology, the Medical Biochemistry Department, Faculty of Medicine, Cairo University, Egypt 2 Medical Biochemistry Department, Faculty of Medicine, Ain Shams University, Egypt 3 Biochemistry Department, Faculty of Science, King Abdul Aziz University, Jeddah Saudi Arabia 4 National Cancer Institute, Cairo University, Egypt Abstract Novel water-soluble curcumin derivatives have been devel- oped to overcome low in vivo bioavailability of curcumin. The aim of this work is to assess the potential utility of certain downstream targets as bioavailability indicators of systemic activity of pure curcumin and two novel water-soluble curcu- min derivatives (NCD) by constructing dose-dependent response curves and to prove whether this novel curcumin derivatives retained, improved, or abolished biological activity of pure curcumin when applied in vivo. Pure curcumin (CUR), curcumin-carboxy derivative (NCD-1), and curcumin protein conjugate (NCD-2) were administered orally to rats at escalat- ing doses: 37, 74, 148, and 296 lM/kg body weight, respec- tively. Plasma levels of GST activity, cavernous tissue levels of cGMP, and enzymatic activity of both HO-1 and GST were assessed one and half and 24 hours after oral administration of curcumin formulae. This study showed that there was a progressive elevation of cavernous tissue levels of cGMP and enzymatic activity of both HO-1 and GST in a dose-dependent manner that was maintained for 24 h with CUR, NCD-1, and NCD-2. Plasma GST activity was decreased by the lowest doses on the curve. The three dose-dependent bioavailability indicators as surrogates of curcumin and two of its novel derivatives are valid in the studied range of concentration and extended time. The novel curcumin derivatives still conserve with improvement the biological activity of natural curcumin when applied in vivo. VC 2013 BioFactors, 40(1):132–137, 2014 Keywords: curcumin; NCD; GST; cGMP; HO-1; bioavailability indicators 1. Introduction Early clinical trials with molecular targeting agents should include the measurement of biomarkers to assess the pharmacodynamic effect of the molecular target and the rele- vant downstream components that may correlate with phar- macologic response. Curcumin, a hydrophobic polyphenol derived from the rhi- zome of the herb Curcuma longa has a wide spectrum of bio- logical and pharmacological activities [1]. Curcumin has been shown to prevent cancer in the colon, skin, stomach, duodenum, soft palate, and breasts of rodents after oral administration [2–4]. Mechanisms by which curcumin prevents cancer are thought to involve upregulation of carcinogen- detoxifying enzymes such as glutathione S-transferases [5,6], antioxidation [7,8], and suppression of oxidative DNA adduct (M1G) formation [9]. VC 2013 International Union of Biochemistry and Molecular Biology Volume 40, Number 1, January/February 2014, Pages 132–137 *Address for correspondence: Fatma Taha, MD, Associate professor of Medical Biochemistry, Faculty of Medicine, Cairo University. E-mail: fatmatahaus@yahoo.com. Received 2 March 2013; accepted 7 May 2013 DOI 10.1002/biof.1118 Published online 19 July 2013 in Wiley Online Library (wileyonlinelibrary.com) 132 BioFactors