Eirini Christodoulou1, Maria-Eleni Grafakou2, Eleni Skaltsa2, Nikolaos Kadoglou3, Nikolaos Kostomitsopoulos4, Georgia Valsami1. 1. Laboratory of Biopharmaceutics and Pharmacokinetics, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece. 2. Laboratory of Pharmacognosy and Natural Products Chemistry, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece. 3. Oxford University, Oxford, UK. 4. Center of Clinical Experimental Surgery and Translational Research, Biomedical Research Foundation, Academy of Athens, Athens, Greece.
Abstract
OBJECTIVES: To prepare a lyophilized saffron aqueous extract (SFE) and determine its chemical profile and serum and tissue pharmacokinetics after intravenous and oral administration to C57/Bl6J mice. METHODS: Lyophilized SFE was prepared, characterized using semi-preparative HPLC and NMR analysis, and stability studies at room temperature, and was quantified for crocin content with an HPLC-PDA method. After intravenous and oral administration of SFE (60 mg/kg, reconstituted with water for injection) to C57/Bl6J mice, crocetin (derived from in vivo crocin hydrolysis) serum and tissue levels (unconjugated and total) were measured with an HPLC-PDA method and subjected to compartmental and non-compartmental PK analysis. KEY FINDINGS: Saffron aqueous extract was rich in all-trans-crocin (27.8 ± 0.1% w/w) and stable for more than 15 months. One-compartment PK model described crocetin's (unconjugated) kinetics after intravenous administration of SFE, while a first-order kinetic parameter described the rate of crocetin biotransformation to crocetin metabolite (conjugated). Α οne-compartment PK model with first-order absorption described crocetin and crocetin's metabolite kinetics after SFE oral administration. Relative oral bioavailability was calculated at 1.17 for total crocetin. Tissue NCA PK analysis revealed extensive crocetin distribution to liver and kidneys. CONCLUSIONS: SFE is a stable lyophilized extract rich in all-trans-crocin. The PK study allowed the estimation of basic PK parameters and the bioavailability of SFE's main bioactive component, crocetin, after peros administration.
OBJECTIVES: To prepare a lyophilized saffron aqueous extract (SFE) and determine its chemical profile and serum and tissue pharmacokinetics after intravenous and oral administration to C57/Bl6J mice. METHODS: Lyophilized SFE was prepared, characterized using semi-preparative HPLC and NMR analysis, and stability studies at room temperature, and was quantified for crocin content with an HPLC-PDA method. After intravenous and oral administration of SFE (60 mg/kg, reconstituted with water for injection) to C57/Bl6J mice, crocetin (derived from in vivo crocin hydrolysis) serum and tissue levels (unconjugated and total) were measured with an HPLC-PDA method and subjected to compartmental and non-compartmental PK analysis. KEY FINDINGS: Saffron aqueous extract was rich in all-trans-crocin (27.8 ± 0.1% w/w) and stable for more than 15 months. One-compartment PK model described crocetin's (unconjugated) kinetics after intravenous administration of SFE, while a first-order kinetic parameter described the rate of crocetin biotransformation to crocetin metabolite (conjugated). Α οne-compartment PK model with first-order absorption described crocetin and crocetin's metabolite kinetics after SFE oral administration. Relative oral bioavailability was calculated at 1.17 for total crocetin. Tissue NCA PK analysis revealed extensive crocetin distribution to liver and kidneys. CONCLUSIONS: SFE is a stable lyophilized extract rich in all-trans-crocin. The PK study allowed the estimation of basic PK parameters and the bioavailability of SFE's main bioactive component, crocetin, after peros administration.
Authors: Kiran Shahbaz; Dennis Chang; Xian Zhou; Mitchell Low; Sai Wang Seto; Chung Guang Li Journal: Front Pharmacol Date: 2022-08-05 Impact factor: 5.988
Authors: Kyriaki Hatziagapiou; Olti Nikola; Sofia Marka; Eleni Koniari; Eleni Kakouri; Maria-Eleftheria Zografaki; Sophie S Mavrikou; Charalabos Kanakis; Emmanouil Flemetakis; George P Chrousos; Spyridon Kintzios; George I Lambrou; Christina Kanaka-Gantenbein; Petros A Tarantilis Journal: Antioxidants (Basel) Date: 2022-05-28