Serum and tissue pharmacokinetics of silibinin after per os and i.v. administration to mice as a HP-β-CD lyophilized product

Christodoulou, Eirini; Kechagia, Irene-Ariadne; Tzimas, Stavros; Balafas, Evangelos; Kostomitsopoulos, Nikolaos; Archontaki, Helen; Dokoumetzidis, Aristides; Valsami, Georgia

doi:10.1016/j.ijpharm.2015.07.060

Cited by 35 publications

(22 citation statements)

References 34 publications

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“…For the determination of crocetin in mice serum and tissue homogenates, a direct precipitation method was applied . About 25 μl of each sample was mixed with 50 μl acetonitrile containing curcumin as IS (1 : 2 v/v – final sample concentration 5 μg/ml) and 5 μl of DMSO.…”

Section: Methodsmentioning

confidence: 99%

“…For the determination of total crocetin in serum and tissue homogenates, 15 μl of each sample was mixed with 45 μl of β‐glucuronidase enzyme diluted in CH 3 COONa/CH 3 COOH (pH adjusted to 5.0) and incubated at 37°C for 1 h in a shaking bath . After vortex‐mixing with 5 μl DMSO and 120 μl of IS (final sample concentration 5 μg/ml) solution and centrifugation at 11200 g for 10 min, 20 μl of the supernatant was directly injected onto the chromatographic system.…”

Section: Methodsmentioning

confidence: 99%

“…For the determination of crocetin in mice serum and tissue homogenates, a direct precipitation method was applied. [31,32] About 25 ll of each sample was mixed with 50 ll acetonitrile containing curcumin as IS (1 : 2 v/vfinal sample concentration 5 lg/ml) and 5 ll of DMSO. After vortex-mixing for 30 s and centrifugation for 10 min at 11200g, 20 ll of the supernatant was directly injected onto the chromatographic system.…”

Section: Crocetin Measurements In Blood and Tissue Samplesmentioning

confidence: 99%

“…For the determination of total crocetin in serum and tissue homogenates, 15 ll of each sample was mixed with 45 ll of b-glucuronidase enzyme diluted in CH 3 COONa/ CH 3 COOH (pH adjusted to 5.0) and incubated at 37°C for 1 h in a shaking bath. [32] After vortex-mixing with 5 ll DMSO and 120 ll of IS (final sample concentration 5 lg/ ml) solution and centrifugation at 11200g for 10 min, 20 ll of the supernatant was directly injected onto the chromatographic system. Crocetin metabolite (conjugated) concentration was calculated by subtraction of measured crocetin (unconjugated) concentration from measured total crocetin (unconjugated + conjugated) concentration.…”

Section: Crocetin Measurements In Blood and Tissue Samplesmentioning

confidence: 99%

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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

Christodoulou

Grafakou

Skaltsa

et al. 2018

Journal of Pharmacy and Pharmacology

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Crocetin Measurements In Blood and Tissue Samplesmentioning

confidence: 99%

Section: Crocetin Measurements In Blood and Tissue Samplesmentioning

confidence: 99%

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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

Christodoulou

Grafakou

Skaltsa

et al. 2018

Journal of Pharmacy and Pharmacology

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“…Nevertheless, in this work, the timing for the administration of pure silybin is not clear, that is without molecules that increase its oral bioavailability, and high-fat diet (HFD) in the group of rats fed with HFD+silybin. Therefore, taking into account the low bioavailability of pure silybin, if administered per os [ 111 ], it cannot exclude that the outcome observed in this study could depend on a reduction of absorption of fat contained in HFD mediated by the formation of non absorbable complexes with silybin, rather than depending on its real role in interrupting the pathogenetic mechanisms that are responsible for NAFLD.…”

Section: Silymarin/silybin In Chronic Liver Diseasementioning

confidence: 99%

Silymarin/Silybin and Chronic Liver Disease: A Marriage of Many Years

2017

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Silymarin is the extract of Silybum marianum, or milk thistle, and its major active compound is silybin, which has a remarkable biological effect. It is used in different liver disorders, particularly chronic liver diseases, cirrhosis and hepatocellular carcinoma, because of its antioxidant, anti-inflammatory and antifibrotic power. Indeed, the anti-oxidant and anti-inflammatory effect of silymarin is oriented towards the reduction of virus-related liver damages through inflammatory cascade softening and immune system modulation. It also has a direct antiviral effect associated with its intravenous administration in hepatitis C virus infection. With respect to alcohol abuse, silymarin is able to increase cellular vitality and to reduce both lipid peroxidation and cellular necrosis. Furthermore, silymarin/silybin use has important biological effects in non-alcoholic fatty liver disease. These substances antagonize the progression of non-alcoholic fatty liver disease, by intervening in various therapeutic targets: oxidative stress, insulin resistance, liver fat accumulation and mitochondrial dysfunction. Silymarin is also used in liver cirrhosis and hepatocellular carcinoma that represent common end stages of different hepatopathies by modulating different molecular patterns. Therefore, the aim of this review is to examine scientific studies concerning the effects derived from silymarin/silybin use in chronic liver diseases, cirrhosis and hepatocellular carcinoma.

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A review of biologically active flavonoids as inducers of autophagy and apoptosis in neoplastic cells and as cytoprotective agents in non‐neoplastic cells

D'Arcy

2022

Cell Biology International

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Phytochemicals are a diverse group of compounds found in various fruits, vegetables, nuts, and legumes. Many phytochemicals have been observed to possess health benefits. Some have been found to be chemoprotective or can act as chemotherapeutics by inducing autophagy, apoptosis, or otherwise regulating the cell cycle. Many also act as potent antioxidants. Flavonoids are a subclass of bioactive phytochemicals consisting of two phenolic benzene rings, joined together by a heterocyclic pyran or pyrone. It has been observed in multiple studies that there is a correlation between diets rich in flavonoids and a reduction in cancer levels, heart disease, neurodegenerative diseases, and other pathologies. As foods containing flavonoids are widely consumed, and their mechanisms of action are still only partially understood, this review was compiled to compare the effects and mechanisms of action of some of the most widely characterized and publicized flavonoids. The flavonoids silibinin, quercetin, isorhamnetin, luteolin, curcumin genkwanin, and acacetin, together with flavonoid extracts from papaw and Tephroseris kirilowii (Turcz) Holub, a member of the Daisy family, were found to be potent regulators of the cell cycle. The decision to overview these specific flavonoids was based on their therapeutic effects, and/or their potential effects. The sparsity of data comparing these flavonoids was also a key consideration. These flavonoids all modulated to some extent the pathways of autophagy and/or apoptosis and regulated the cell cycle, inflammation, and free radical levels. This explains why they are protective of healthy or moderately damaged cells, but toxic to neoplastic or pre-cancerous cells.

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Serum and tissue pharmacokinetics of silibinin after per os and i.v. administration to mice as a HP-β-CD lyophilized product

Cited by 35 publications

References 34 publications

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

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

Silymarin/Silybin and Chronic Liver Disease: A Marriage of Many Years

A review of biologically active flavonoids as inducers of autophagy and apoptosis in neoplastic cells and as cytoprotective agents in non‐neoplastic cells

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