||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).|
|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.
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]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.
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.
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.|