• Biomolecules & Therapeutics
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• v.25 no.4
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• pp.441-451
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• 2017

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.

• Archives of Pharmacal Research
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• v.9 no.2
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• pp.81-86
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• 1986

The effect of imperatorin on hepatic microsomal mixed function oxidases (MF0) was investigated. On acute treatment, imperatorin (30 mg/kg, i.p) caused a significant reduction in activities of hepatic aminopyrine N-demethylase, hexobarbital hydroxylase and aniline hydroxylase as well as cytochrome p0450 content in rats and mice. Kinetic studies on rat liver enzymes revealed that imperatorin appeared to be a competitive inhibitor of aminopyrine N-demethylase (Ki,0.007 mM), whereas a non-competitive inhibitor of hexobarbital hydroxylase (Ki, 0.0148 mM). Imperatorin also inhibited non-competitively aniline metabolism (Ki 0.2 mM). Imperatorin binds to phenobarbital-induced cytochrome p-450 to give a typical type 1 binding sepctrum (max. 388nm, min 422 nm). Multiple administrations of imperatorin (30 mg/kg. i. p. daily for 7 days) to mice shortended markedly the duration of hexobarbital narcosis and increased activities of hepatic aminopyrine N-demethylase and hexobarbital hydroxylase and the level of cytochrome p-450 where as aniline hydroxylase activity was unaffected.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.1028-1035
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• 2004

Imperatorin, a biologically active furanocoumarin from the roots of Angelica dahurica (Umbelliferae), was mutagenic and induced transformation of mouse fibroblast cell lines, whereas it provided inhibiting effects on mutagenesis and carcinogenesis induced by various carcinogens. Furthermore, it has been suggested that imperatorin may have potential anticarcinogenic effects when administered orally in the diet. In addition to its anticarcinogenic properties, imperatorin has been shown to possess anticancer activities. We investigated the macro scale gene expression analysis on the HL-60 cells treated with imperatorin. Imperatorin (10μM) were used to treat the cells for 6h, 12h, 24h, 48h, and 72h. In a human cDNAchip study of 10,000 genes evaluated 6, 12, 24, 48, 72 hours after treated with imperatorin in HL-60 cells. Hierarchical cluster against the genes which showed expression changes by more than 2 fold. Three hundred eighty six genes were grouped into 6 clusters by a hierarchical clustering algorithm. Pathway analysis using gene microarray pathway prof Her that is a computer application designed to visualize gene expression data on screen representing biological pathways and groupings of genes.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.4
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• pp.399-406
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• 2016

Early life neuronal exposure to environmental toxicants has been suggested to be an important etiology of neurodegenerative disease development. Perfluorohexanesulfonate (PFHxS), one of the major perfluoroalkyl compounds, is widely distributed environmental contaminants. We have reported that PFHxS induces neuronal apoptosis via ERK-mediated pathway. Imperatorin is a furanocoumarin found in various edible plants and has a wide range of pharmacological effects including neuroprotection. In this study, the effects of imperatorin on PFHxS-induced neuronal apoptosis and the underlying mechanisms are examined using cerebellar granule cells (CGC). CGC were isolated from seven-day old rats and were grown in culture for seven days. Caspase-3 activity and TUNEL staining were used to determine neuronal apoptosis. PFHxS-induced apoptosis of CGC was significantly reduced by imperatorin and PD98059, an ERK pathway inhibitor. PFHxS induced a persistent increase in intracellular calcium, which was significantly blocked by imperatorin, NMDA receptor antagonist, MK801 and the L-type voltage-dependent calcium channel blockers, diltiazem and nifedipine. The activation of caspase-3 by PFHxS was also inhibited by MK801, diltiazem and nifedipine. PFHxS-increased ERK activation was inhibited by imperatorin, MK801, diltiazem and nifedipine. Taken together, imperatorin protects CGC against PFHxS-induced apoptosis via inhibition of NMDA receptor/intracellular calcium-mediated ERK pathway.

• YAKHAK HOEJI
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• v.8 no.4
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• pp.94-95
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• 1964

Ether extract of the fruits of Angelica gigas NAKAI(Umbelliferae) growing wild and cultivating in Korea, afforded frocoumarin derivative, imperatorin which was identified through physical constants-I.R.spectrum, paper partition chromatography, and preparation of derivatives.

• Biomolecules & Therapeutics
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• v.23 no.5
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• pp.421-427
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• 2015

Imperatorin has been known to exert many biological functions including anti-inflammatory activity. In this study, we investigated the inhibitory effects of imperatorin on the production of inflammatory mediators in mouse bone marrow-derived mast cells (BMMC). Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene $C_4$ ($LTC_4$) and prostaglandin $D_2$ ($PGD_2$) in IgE/antigen (Ag)-stimulated BMMC. To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC. Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent $LTC_4$ and cyclooxygenase-2-dependent $PGD_2$ through the inhibition of intracellular calcium influx/phospholipase $C{\gamma}1$, cytosolic phospholipase $A_2$/mitogen-activated protein kinases and/or nuclear factor-${\kappa}B$ pathways in BMMC. These results suggest that the effects of imperatorin on inhibition of degranulation and eicosanoid generation through the suppression of multiple steps of IgE/Ag-mediated signaling pathways would be beneficial for the prevention of allergic inflammation.

• Biomolecules & Therapeutics
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• v.14 no.4
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• pp.235-239
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• 2006

Angelicae Koreanae Radix has been used for controlling inflammatory respiratory diseases in folk medicine and their components, imperatorin, marmesinin and oxypeucedanin were reported to have diverse biological effects. In this study, we investigated whether imperatorin, marmesinin and oxypeucedanin affect adenosine triphosphate(ATP)-induced mucin secretion from cultured airway epithelial cells. Confluent primary hamster tracheal surface epithelial(HTSE) cells were metabolically radiolabeled using $^3H$-glucosamine for 24 h and chased for 30 min in the presence of varying concentrations of each agent to assess the effects on $^3H$-mucin secretion. The results were as follows: 1) imperatorin significantly inhibited ATP-induced mucin secretion; 2) However, marmesinin and oxypeucedanin did not affect ATP-induced mucin secretion, significantly. We conclude that imperatorin might inhibit ATP-induced mucin secretion by directly acting on airway mucin-secreting cells. Therefore, imperatorin should further be investigated for the possible use as mucoregulators in the treatment of inflammatory airway diseases.

• Korean Journal of Pharmacognosy
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• v.6 no.3
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• pp.149-150
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• 1975

Silicagel colum chromatography of the ether extract of the fruits of Angelica decursiva $F_R$. et SAV. gave four crystalline products of coumarins and one steroid. The following furocoumarins and ${\beta}-sitosterol$ were identifed by UV, IR, NMR spectra and physicochemical tests: ${\beta}-sitosterol$, iso-imperatorin, imperatorin, bergapten, umbelliferone.

• Korean Journal of Crystallography
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• v.9 no.2
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• pp.114-119
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• 1998

Imperatorin, 9-[(3-methyl-2-butenyl)oxy]-7H-furo[3,2-g][1]benzopyran-7-one의 분자 및 결정구조를 X-선 회절법으로 연구하였다. 이 결정의 분자식은 C16H14O4, 결정계는 삼사정계이고 공간군은 P이다. 단위포상수는 a=11.818(1) , b=11.906(1) , c=11.059(1) 이며, α=96.32(1)o, β=90.74(1)o, γ=64.88(1)o, V=13.993(2) 3, T=293 K, Z=4이다. 구조해석에 사용한 X-선은 CuKα선(λ=1.5418 )을 사용하였다. 구조는 직접법으로 풀었으며 최소자승법으로 정밀화하였다. 최종 신뢰도 R 값은 F0>4σ(F0)인 3951개의 독립회절데이타로 356개 파라메타에 대해 R=7.02%이다.

• 대한한약학회:학술대회논문집
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• 2007.11a
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• pp.187-188
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• 2007