title: Dose-dependent bioavailability indicators for curcumin and two of its novel derivatives.
abstract: Novel water-soluble curcumin derivatives have been developed 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 curcumin 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 escalating doses: 37, 74, 148, and 296 μM/kg body weight, respectively. 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.
authors.affiliation: Unit of Biochemistry and Molecular Biology, the Medical Biochemistry Department, Faculty of Medicine, Cairo University, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abd el Aziz
authors.forename: Mohamed
authors.initials: M
authors.lastname: El-Asmer
authors.forename: Ameen
authors.initials: A
authors.lastname: Rezq
authors.forename: Abdulrahman
authors.initials: A
authors.lastname: Al-Malki
authors.forename: Taha
authors.initials: T
authors.lastname: Kumosani
authors.forename: Hanan
authors.initials: H
authors.lastname: Fouad
authors.forename: Hanan
authors.initials: H
authors.lastname: Ahmed
authors.forename: Fatma
authors.initials: F
authors.lastname: Taha
authors.forename: Amira
authors.initials: A
authors.lastname: Hassouna
authors.forename: Hafez
authors.initials: H
authors.lastname: Hafez
mesh_terms: D000284:Administration, Oral; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001391:Azo Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D003474:Curcumin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D016588:Anticarcinogenic Agents; D001391:Azo Compounds; D003474:Curcumin
keywords: GST; HO-1; NCD; bioavailability indicators; cGMP; curcumin