Binding of Crocetin to Plasma Albumin

Miller, Theodore L.; Willett, Steven L.; Moss, Maryanne E.; Miller, J. N.; Belinka, Benjamin A.

doi:10.1002/jps.2600710209

Cited by 32 publications

(19 citation statements)

References 22 publications

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“…e distribution volume obtained in this work was 3.18 L, which is related to compounds that bind strongly with plasma proteins as albumin [44], reducing its free content in blood. It correlates with the previous works which described that crocetin binds to albumin [45,46] and other human serum proteins [47]. After 3 h of administration, crocetin ceased to be detected, obtaining a plasmatic half-life of 0.85 ± 0.04 h and a clearance of 2.70 ± 0.14 L/h.…”

Section: Discussionsupporting

confidence: 90%

Bioaccessibility and Pharmacokinetics of a Commercial Saffron (Crocus sativus L.) Extract

Almodóvar¹,

Briskey

Rao³

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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There are few studies about the pharmacokinetics of the low-molecular mass carotenoids crocetin or crocin isomers from saffron (Crocus sativus L.). None has been performed with a galenic preparation of a standardised saffron extract. The aim of the present research work was to study the effect of in vitro digestion process on the main bioactive components of saffron extract tablets and the corresponding pharmacokinetic parameters in humans. Pharmacokinetics were calculated collecting blood samples every 30 min during the first 3 h and at 24 h after administration of two different concentrations (56 and 84 mg of the saffron extract) to 13 healthy human volunteers. Additionally, an in vitro digestion process was performed in order to determine the bioaccessibility of saffron main bioactive compounds. Identification and quantification analysis were performed by HPLC-PAD/MS. Digestion resulted in 40% of bioaccesibility for crocin isomers, whereas, safranal content followed an opposite trend increasing about 2 folds its initial concentration after the digestion process. Crocetin in plasma was detected in a maximum concentration (Cmax) in blood between 60 and 90 min after oral consumption with dose-dependent response kinetics, showing that crocin isomers from galenic preparation of saffron extract are rapidly transformed into crocetin. The results showed that this tested galenic form is an efficient way to administer a saffron extract, since the observed crocetin Cmax was similar and more quickly bioavailable than those obtained by other studies with much higher concentrations of crocetin.

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Section: Discussionsupporting

confidence: 90%

Bioaccessibility and Pharmacokinetics of a Commercial Saffron (Crocus sativus L.) Extract

Almodóvar¹,

Briskey

Rao³

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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“…CRT can bind to albumin in blood plasma by occupying fatty acid binding sites so that CRT can be distributed into different tissues 39,40 . CRT was reported to be able to penetrate the BBB in vitro and in vivo 41,42 .…”

mentioning

confidence: 99%

Delivering Crocetin across the Blood-Brain Barrier by Using γ-Cyclodextrin to Treat Alzheimer’s Disease

Wong

Xie

Huang

et al. 2020

Sci Rep

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Crocetin (CRT) has shown various neuroprotective effects such as antioxidant activities and the inhibition of amyloid β fibril formation, and thus is a potential therapeutic candidate for Alzheimer's disease (AD). However, poor water solubility and bioavailability are the major obstacles in formulation development and pharmaceutical applications of cRt. in this study, a novel water-soluble cRt-γcyclodextrin inclusion complex suitable for intravenous injection was developed. the inclusion complex was nontoxic to normal neuroblastoma cells (N2a cells and SH-SY5Y cells) and AD model cells (7PA2 cells). furthermore, it showed stronger ability to downregulate the expression of c-terminus fragments and level of amyloid β in 7PA2 cell line as compared to the CRT free drug. Both inclusion complex and CRT were able to prevent SH-SY5Y cell death from H 2 o 2-induced toxicity. the pharmacokinetics and biodistribution studies showed that cRt-γ-cyclodextrin inclusion complex significantly increased the bioavailability of cRt and facilitated cRt crossing the blood-brain barrier to enter the brain. this data shows a water-soluble γ-cyclodextrin inclusion complex helped to deliver cRt across the blood-brain barrier. this success should fuel further pharmaceutical research on cRt in the treatment for AD, and it should engender research on γ-cyclodextrin with other drugs that have so far not been explored. Alzheimer's disease (AD) is an irreversible neurodegenerative disease which cannot be cured by any therapeutic approaches up to now 1. As the number of AD patients increases, the need to develop safe, effective drugs for AD therapy becomes increasingly urgent. In traditional herbal medicine, several plants have been used to treat the symptoms of neurodegenerative diseases 2,3. Crocetin (CRT) is an active compound isolated from the fruits of gardenia (Gardenia jasminoides Ellis) and the stigmas of saffron (Crocus sativus L.) 4. Various pharmacological activities of CRT have been reported. CRT can inhibit amyloid β (Aβ) fibril formation, destabilize pre-formed Aβ fibrils and improve Aβ degradation in vitro 5,6. CRT can also reduce Aβ 1-42-induced neurotoxicity by attenuating oxidative stress in murine hippocampal cells 7. Furthermore, CRT can reduce the production of various neurotoxic molecules from neuron, such as lipopolysaccharide (LPS)-induced nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and reactive oxygen species (ROS), which provided strong protection from neuronal cell death 8,9. Moreover, CRT has been proven to cross the blood-brain barrier (BBB) limitedly after administration 10. The mentioned properties of CRT indicate that it may be a potentially useful candidate for AD treatment. In terms of its chemical structure (Fig. 1A), CRT contains two carboxylic acid groups at each end of a polyene chain. However, CRT is insoluble in water in the physiological range (0.0056 g/L); it can only slightly dissolve in pyridine, dimethyl sulfoxide or aqueous alkali solutions at pH above 9 11. Poor solub...

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“…The obtained results have indicated significant inhibition in the synthesis of nucleic acids in malignant human cell lines [14,15], disruption in DNA-protein interactions by dimethyl crocetin [14] and dose-dependent inhibitory effect of crocetin on intracellular nucleic acid of the isolated nuclei [15]. Also, a few in vitro studies have been performed on crocetin binding to albumin and the induction of conformational changes on it [44,45,53].…”

Section: Discussionmentioning

confidence: 81%

The effect of carotenoids obtained from saffron on histone H1 structure and H1–DNA interaction

Ashrafi

Bathaie

Taghikhani

et al. 2005

International Journal of Biological Macromolecules

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Binding of Crocetin to Plasma Albumin

Cited by 32 publications

References 22 publications

Bioaccessibility and Pharmacokinetics of a Commercial Saffron (Crocus sativus L.) Extract

Bioaccessibility and Pharmacokinetics of a Commercial Saffron (Crocus sativus L.) Extract

Delivering Crocetin across the Blood-Brain Barrier by Using γ-Cyclodextrin to Treat Alzheimer’s Disease

The effect of carotenoids obtained from saffron on histone H1 structure and H1–DNA interaction

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