Brain Distribution Study of Imperatorin in Rats after Oral Administration Assessed by HPLC

Zhang, Xiaokai; Xie, Youhua; Cao, Wei; Yang, Qian; Miao, Song; Wang, Siwang

doi:10.1007/s10337-011-2073-8

Cited by 10 publications

(7 citation statements)

References 14 publications

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“…This result is consistent with the tissue-to-plasma ratios of the three components being greater than unity in most brain tissues at 2 h following multiple oral administrations of DA-9805. PA and IMP pass through the blood–brain barrier [ 14 , 32 ]. The concentrations of IMP in the striatum and hippocampus are higher than those in other regions [ 32 ]; our results are consistent with those findings.…”

Section: Discussionmentioning

confidence: 99%

“…It has anti-inflammatory effects [ 25 , 26 ] and other favorable effects in the central nervous system (CNS) including neuroprotective, anticonvulsant, anxiolytic, and procognitive activities [ 27 , 28 , 29 ]. Its PKs following intravenous and oral administration (6.25–25 mg/kg or 80 mg/kg) in rats have been reported [ 30 , 31 ], as has its brain distribution after oral administration of 20 mg/kg of IMP [ 32 ] or ~26 mg/kg in an extract [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics and Brain Distribution of the Active Components of DA-9805, Saikosaponin A, Paeonol and Imperatorin in Rats

et al. 2018

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DA-9805 is a botanical anti-Parkinson’s drug candidate formulated from ethanol extracts of the root of Bupleurum falcatum, the root cortex of Paeonia suffruticosa, and the root of Angelica dahurica. The pharmacokinetics (PKs) and brain distribution of active/representative ingredients of DA-9805, Saikosaponin a (SSa; 1.1–4.6 mg/kg), Paeonol (PA; 14.8–59.2 mg/kg), and Imperatorin (IMP; 1.4–11.5 mg/kg) were evaluated following the intravenous or oral administration of each pure component and the equivalent dose of DA-9805 in rats. All three components had greater dose-normalized areas under the plasma concentration-time curve (AUC) and slower clearance with higher doses, following intravenous administration. By contrast, dose-proportional AUC values of SSa, PA, and IMP were observed following the oral administration of each pure component (with the exception of IMP at the highest dose) or DA-9805. Compared to oral administration of each pure compound, DA-9805 administration showed an increase in the AUC of SSa (by 96.1–163%) and PA (by 155–164%), possibly due to inhibition of their metabolism by IMP or other component(s) in DA-9805. A delay in the absorption of PA and IMP was observed when they were administered as DA-9805. All three components of DA-9805 showed greater binding values in brain homogenates than in plasma, possibly explaining why the brain-to-plasma ratios were greater than unity following multiple oral administrations of DA-9805. By contrast, their levels in cerebrospinal fluid were negligible. Our results further our understanding of the comprehensive PK characteristics of SSa, PA, and IMP in rats and the comparative PKs between each pure component and DA-9805.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and Brain Distribution of the Active Components of DA-9805, Saikosaponin A, Paeonol and Imperatorin in Rats

et al. 2018

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“…It also can be distributed into many regions in rat brain such as cortex, striatum, and hippocampus (Zhang et al ., 2011). Lee et al .…”

Section: Discussionmentioning

confidence: 99%

Imperatorin is Transported through Blood-Brain Barrier by Carrier-Mediated Transporters

Tun

Kang

2017

Biomolecules & Therapeutics

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Imperatorin, a major bioactive furanocoumarin with multifunctions, can be used for treating neurodegenerative diseases. In this study, we investigated the characteristics of imperatorin transport in the brain. Experiments of the present study were designed to study imperatorin transport across the blood-brain barrier both in vivo and in vitro. In vivo study was performed in rats using single intravenous injection and in situ carotid artery perfusion technique. Conditionally immortalized rat brain capillary endothelial cells were as an in vitro model of blood-brain barrier to examine the transport mechanism of imperatorin. Brain distribution volume of imperatorin was about 6 fold greater than that of sucrose, suggesting that the transport of imperatorin was through the blood-brain barrier in physiological state. Both in vivo and in vitro imperatorin transport studies demonstrated that imperatorin could be transported in a concentration-dependent manner with high affinity. Imperatorin uptake was dependent on proton gradient in an opposite direction. It was significantly reduced by pretreatment with sodium azide. However, its uptake was not inhibited by replacing extracellular sodium with potassium or N-methylglucamine. The uptake of imperatorin was inhibited by various cationic compounds, but not inhibited by TEA, choline and organic anion substances. Transfection of plasma membrane monoamine transporter, organic cation transporter 2 and organic cation/carnitine transporter 2/1 siRNA failed to alter imperatorin transport in brain capillary endothelial cells. Especially, tramadol, clonidine and pyrilamine inhibited the uptake of [3H]imperatorin competitively. Therefore, imperatorin is actively transported from blood to brain across the blood-brain barrier by passive and carrier-mediated transporter.

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“…The highest concentrations were detected in the striatum, hippocampus, brain stem, cortex, cerebellum, and diencephalon, respectively. The half-life in the hippocampus was significantly longer than in other structures (Zhang et al 2011a ).…”

Section: Pharmacokinetics Of Imperatorinmentioning

confidence: 99%

Imperatorin–pharmacological meaning and analytical clues: profound investigation

Kozioł

Skalicka-Woźniak

2016

Phytochem Rev

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Imperatorin, a furanocoumarin derivative, has many documented pharmacological properties which make it a candidate for possible drug development. In this review, the activity on the central nervous system, the anticancer and antiviral properties and the influence on the cardiovascular system are described. The aim of this review is also to present an overview of the techniques used for the analysis, isolation, and separation of imperatorin from plant material from the practical perspective.

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Brain Distribution Study of Imperatorin in Rats after Oral Administration Assessed by HPLC

Cited by 10 publications

References 14 publications

Pharmacokinetics and Brain Distribution of the Active Components of DA-9805, Saikosaponin A, Paeonol and Imperatorin in Rats

Pharmacokinetics and Brain Distribution of the Active Components of DA-9805, Saikosaponin A, Paeonol and Imperatorin in Rats

Imperatorin is Transported through Blood-Brain Barrier by Carrier-Mediated Transporters

Imperatorin–pharmacological meaning and analytical clues: profound investigation

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