| Description: |
Isoimperatorin has analgesic, hepatoprotective, antimicrobial, anti-inflammatory, vascular relaxing and anticancer activities. It inhibited the expression of COX, TNF-α, PPAR-γ,ERK1/2, PI3K, and PKC. It showed significant inhibitory effects on acetylcholinesterase (AChE) with the IC50 of 74.6 uM, it also showed different inhibitory effects on all of the six CYP isoenzymes(human CYP1A2, 2B6, 2C9, 2C19, 2D6 and 3A4 enzymes). |
| In vitro: |
| Lett Appl Microbiol. 2014 Apr;58(4):344-9. | | In vitro activity of isoimperatorin, alone and in combination, against Mycobacterium tuberculosis.[Pubmed: 24330002] | Previous studies have shown that isoimperatorin (IO), a furanocoumarin isolated from several medicinal plants, has antimycobacterial activity against Mycobacterium tuberculosis strain H37Rv (ATCC 27294).
METHODS AND RESULTS:
This study demonstrated that IO has antimycobacterial activity against 2 drug-sensitive and 6 drug-resistant isolates, with minimum inhibitory concentrations (MICs) of 50-100 μg ml(-1) and 100-200 μg ml(-1), respectively. IO exhibited synergistic antimycobacterial effects with rifampin (RMP), isoniazid (INH) and ethambutol (EMB) against 6 drug-resistant strains, with fractional inhibitory concentration index (FICI) values of 0·133-0·472, 0·123-0·475 and 0·124-0·25, respectively. The IO/RMP, IO/INH and IO/EMB combination treatments had synergistic effects or no interaction in the 2 drug-sensitive strains and the standard strain ATCC 27294. The synergism of combined drugs against drug-resistant strains was better than drug-sensitive strains. No antagonism was observed in with the aforementioned combinations against all strains tested. IO exhibited relatively low cytotoxicity to Vero cells. Our results indicate that IO may serve as promising a template for future antimycobacterial drug development.
CONCLUSIONS:
This is the first report on the in vitro synergistic antimycobacterial effects of isoimperatorin (IO) in combination with three first-line drugs: rifampin (RMP), isoniazid (INH) and ethambutol (EMB). The results indicated that the antimycobacterial activity of IO was modest; however, IO was a useful and effective agent against Myco. tuberculosis when it was combined with first-line antimycobacterial drugs and is worthy of further development as a lead compound for the development of novel antimycobacterial therapeutic agents. | | Arch Pharm Res. 2008 Feb;31(2):210-5. | | The effects of isoimperatorin isolated from Angelicae dahuricae on cyclooxygenase-2 and 5-lipoxygenase in mouse bone marrow-derived mast cells.[Pubmed: 18365692] | Isoimperatorin (4-[(3-Methyl-2-butenyl)oxy]-7H-furo[3,2-g][1]benzopyran-7-one) is a medicinal herbal product that is isolated from the dried roots of Angelicae dahuricae.
METHODS AND RESULTS:
Isoimperatorin inhibits the cyclooxygenase-2 (COX-2) and COX-1-dependent phases of prostaglandin D2 (PGD2) generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner, with IC50 values of 10.7 microM and 24 microM, respectively. However, this compound was not able to inhibit COX-1 and 2 protein expression in BMMC that were treated with concentrations of up to 50 microM, which indicates that isoimperatorin directly inhibits COX-2 activity. Furthermore, this compound consistently inhibited the production of leukotriene C4 (LTC4), as well as the degranulation reaction in BMMC, with an IC50 value of 5.7 microM and 9 microM, respectively, and these effects occurred in a dose dependent fashion.
CONCLUSIONS:
These results demonstrate that isoimperatorin has a dual cyclooxygenase-2 selective/5-lipoxygenase inhibitory activity, and therefore may provide the basis for novel anti-inflammatory drugs. | | J Ethnopharmacol. 2011 Jan 27;133(2):336-44. | | Isoimperatorin, cimiside E and 23-O-acetylshengmanol-3-xyloside from Cimicifugae rhizome inhibit TNF-α-induced VCAM-1 expression in human endothelial cells: involvement of PPAR-γ upregulation and PI3K, ERK1/2, and PKC signal pathways.[Pubmed: 20937376 ] | | Pretreatment of test compounds significantly reduced reactive oxygen species (ROS) production and expression of vascular cell adhesion molecule-1 (VCAM-1), but not intercellular cell adhesion molecule-1 (ICAM-1). Three compounds all dose-dependently increased not only PPAR-γ expression in EA.hy926 cells but inhibited TNF-α-induced phosphorylation of Akt, extracellular-signal-regulated kinase (ERK) and protein kinase C (PKC) with different specificity. Finally, they prevented TNF-α-induced adhesion of U937 monocytic cells to EA.hy926 cells.
CONCLUSIONS:
The present results show that cimiside E, 23-O-actylshengmanol-3-xyloside, isoimperatorin isolated from Cimicifugae Rhizome selectively inhibits TNF-α-induced expression of VCAM-1 at least by upregulation of PPAR-γ, and signals for ERK1/2, PI3K, and PKC are involved in this effect. | | 2016 Sep 23;21(10):1276. | | Identification of Nematicidal Constituents of Notopterygium incisum Rhizomes against Bursaphelenchus xylophilus and Meloidogyne incognita[Pubmed: 27669203] | | Abstract
During a screening program for new agrochemicals from Chinese medicinal herbs, the ethanol extract of Notopterygium incisum rhizomes was found to possess strong nematicidal activity against the two species of nematodes, Bursaphelenchus xylophilus and Meloidogyne incognita. Based on bioactivity-guided fractionation, the four constituents were isolated from the ethanol extract and identified as columbianetin, falcarindiol, falcarinol, and isoimperatorin. Among the four isolated constituents, two acetylenic compounds, falcarindiol and falcarinol (2.20-12.60 μg/mL and 1.06-4.96 μg/mL, respectively) exhibited stronger nematicidal activity than two furanocoumarins, columbianetin, and isoimperatorin (21.83-103.44 μg/mL and 17.21-30.91 μg/mL, respectively) against the two species of nematodes, B. xylophilus and M. incognita. The four isolated constituents also displayed phototoxic activity against the nematodes. The results indicate that the ethanol extract of N. incisum and its four isolated constituents have potential for development into natural nematicides for control of plant-parasitic nematodes.
Keywords: Bursaphelenchus xylophilus; Meloidogyne incognita; Notopterygium incisum; nematicidal activity. | | 2016 Jul 8;11(7):e0158796. | | Angelica dahurica Extracts Improve Glucose Tolerance through the Activation of GPR119[Pubmed: 27391814] | | Abstract
G protein-coupled receptor (GPR) 119 is expressed in pancreatic β-cells and intestinal L cells, and is involved in glucose-stimulated insulin secretion and glucagon-like peptide-1 (GLP-1) release, respectively. Therefore, the development of GPR119 agonists is a potential treatment for type 2 diabetes. We screened 1500 natural plant extracts for GPR119 agonistic actions and investigated the most promising extract, that from Angelica dahurica (AD), for hypoglycemic actions in vitro and in vivo. Human GPR119 activation was measured in GeneBLAzer T-Rex GPR119-CRE-bla CHO-K1 cells; intracellular cAMP levels and insulin secretion were measured in INS-1 cells; and GLP-1 release was measured in GLUTag cells. Glucose tolerance tests and serum plasma insulin levels were measured in normal C57BL6 mice and diabetic db/db mice. AD extract-treated cells showed significant increases in GPR119 activation, intracellular cAMP levels, GLP-1 levels and glucose-stimulated insulin secretion as compared with controls. In normal mice, a single treatment with AD extract improved glucose tolerance and increased insulin secretion. Treatment with multiple doses of AD extract or n-hexane fraction improved glucose tolerance in diabetic db/db mice. Imperatorin, phellopterin and isoimperatorin were identified in the active fraction of AD extract. Among these, phellopterin activated GPR119 and increased active GLP-1 and insulin secretion in vitro and enhanced glucose tolerance in normal and db/db mice. We suggest that phellopterin might have a therapeutic potential for the treatment of type 2 diabetes. | | 2016 Oct 14;10:62. | | The pharmacokinetics, bioavailability and excretion of bergapten after oral and intravenous administration in rats using high performance liquid chromatography with fluorescence detection[Pubmed: 27795734] | | Abstract
A sensitive, specific, reproducible and optimized high performance liquid chromatography with fluorescence detection (HPLC-FLD) method for the determination of bergapten in rat plasma was established and applied to the pharmacokinetic and bioavailability study in rat after oral and intravenous administration of bergapten. The method was also successfully applied to the excretion study of bergapten after an oral administration of bergapten at a dose of 15 mg kg-1 to rats. The sample preparation was achieved using liquid-liquid extraction. Isoimperatorin was used as the internal standard (IS). The analytes were detected by using fluorescence detection at an excitation and emission wavelength of 288 and 478 nm, respectively. Using aqueous formic acid (0.1 %, v/v) and acetonitrile as the mobile phase, the chromatographic separation was achieved on a Hedera™ ODS column at a flow rate of 1 mL min-1. The lower limit of quantitation (LLOQ) of bergapten was 2 ng mL-1. The HPLC-FLD method was successfully applied to the pharmacokinetic, bioavailability and excretion study of bergapten in rats.Graphical abstractAn high performance liquid chromatography with fluorescence detection (HPLC-FLD) method for the pharmacokinetic and bioavailability study in rat after administration of bergapten. |
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