Preparation, chemical characterization and determination of crocetin's pharmacokinetics after oral and intravenous administration of saffron (Crocus sativus L.) aqueous extract to C57/BL6J mice

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.

Bioanalytical Method Development and Validation Study of Neuroprotective Extract of Kashmiri Saffron Using Ultra-Fast Liquid Chromatography-Tandem Mass Spectrometry (UFLC-MS/MS): In Vivo Pharmacokinetics of Apocarotenoids and Carotenoids

“…Some pharmacokinetic studies on CS reported that the intestinal deglycosylation of various crocins is primarily due to the enzymatic processes in the epithelial cells. In these reports, minor crocins may be deglycosylated by the fecal microbiome, facilitating transformation into TCT finally [36,37]. The values of C max and AUC 0−t of TCT in the present study were much higher than other crocins.…”

“…The data for bioanalytical studies showed that HPLC-based quantification had been reported for the presence of trans-4-GG-crocin (T4C) or crocin-1 and trans-crocetin (TCT) in CS [4,[35][36][37]. But there is no report of the methodology for bioactive apocarotenoids PIC and SAF along with other carotenoids trans-3-Gg-crocin (T3C), trans-2-gg-crocin (T2C), cis-4-GG-crocin (C4C) from CS [35][36][37]. This research also lacks confirmation and detection of these compounds in biological samples after CS or its extract or product consumption.…”

Bioactivity and Bioavailability of the Major Metabolites of Crocus sativus L. Flower

“…Crocetin levels in blood were higher after oral administration than in intravenous administration, probably due to the wide hydrolysis of the crocins in the intestinal lumen to trans -crocetin, which is rapidly absorbed by passing blood through the portal vein. The analysis of the tissues reveals an extensive distribution of crocetin in the liver and kidneys [108]. The advances in the knowledge of the bioaccesibility of bioactive compounds of saffron will contribute to developing their biomedical applications.…”

Prospects of Saffron and its Derivatives in Alzheimer’s Disease

“…54,57,58 According to a recent study in 2019, fast intestinal absorption of saffron extracts leads to a higher serum level of crocetin compared with intravenous administration. 59 The active components of saffron have been shown to possess antidepressant and antitumor effects, while they are able to neutralize free radicals and reduce inflammation. 20,21 Taken together, saffron might be a candidate for research on neurodegenerative diseases.…”