Effects of furocoumarins fromCachrys trifidaon some macrophage functions

Abstract

Phytochemical and biological studies aimed at the discovery and development of novel antiinflammatory agents from natural sources have been conducted in our laboratory for a number of years. In this communication, three naturally occurring furocoumarins (imperatorin, isoimperatorin and prantschimgin) were evaluated as potential inhibitors of some macrophage functions involved in the inflammatory process. These furocoumarins have been tested in two experimental systems: ionophore-stimulated mouse peritoneal macrophages serve as a source of cyclooxygenase-1 and 5-lipoxygenase, and mouse peritoneal macrophages stimulated with E. coli lipopolysaccharide are the means of testing for anti-cyclooxygenase-2 and nitric-oxidesynthase activity. All above-mentioned furocoumarins showed significant effect on 5-lipoxygenase (leukotriene C4) with IC50 values of < 15 microM. Imperatorin and isoimperatorin exhibited strong-to-medium inhibition on cyclooxygenase-1- and cyclooxygenase-2-catalysed prostaglandin E2 release, with inhibition percentages similar to those of the reference drugs, indometacin and nimesulide, respectively. Of the three furocoumarins, only imperatorin caused a significant reduction of nitric oxide generation. Imperatorin and isoimperatorin can be classified as dual inhibitors, since it was evident that both cyclooxygenase and lipoxygenase pathways of arachidonate metabolism were inhibited by these compounds. However, selective inhibition of the 5-lipoxygenase pathway is suggested to be the primary target of action of prantschimgin.

Inhibition of 5-Lipoxygenase Product Synthesis by Natural Compounds of Plant Origin

“…This compound showed marked effectiveness in carrageenan-induced rat paw edema after oral administration (ED 50 = 0.03 mg/kg) [138]. Also other monohydroxylated (osthenol 69 and psoralidin 73 [52], [53], [105]) or O-alkyl derivatives (osthol 70 and imperatorin 71, that lack free phenolic hydroxy groups at all [52], [53], [139]) inhibit 5-LO product synthesis, albeit less efficiently. The latter compounds contain prenyl residues that apparently govern interference with 5-LO product formation.…”

Chemistry and Biological Activity of Natural and Synthetic Prenyloxycoumarins †

“…When tested as an anti-inflammatory agent it exerted a remarkable inhibitory activity on lipopolysaccharide-induced production of prostaglandin E 2 in rat peritoneal macrophages [44], and showed a significant effect on 5-lipoxygenase [62]. As it was shown to be phototoxic [103][104], imperatorin might be used for the treatment of skin diseases such as psoriasis, mycoses and vitiligo, although this therapeutic potential has not been assessed until now.…”

“…Recently DiGiovanni and coworkers exhaustively studied imperatorin both as inhibitor of human cytochrome P450 and as blocker of DNA adduct formation with benzo [41][42] Ammi majus, [43] Angelica spp., [44] Atalantia ceylanica, [45] Citrus spp., [46] Cnidium monnieri, [47][48] Decatropis bicolor, [49] Ferula sumbul, [50] Foeniculum vulgare, [51] Glehnia littoralis, [52] Heracleum spp., [53][54] Leptothyrsa sprucei, [55] Murraya koenigii, [56] Niphogeton ternata, [57] Opopanax chironium, [58] Peucedanum spp., [59] Phebalium spp., [19,60] Poncirus trifoliata, [61] Prangos spp., [62][63] Ptelia baldwanii, [61] Ruta spp., [64] Stauranthus perforatus, [65] Thamnosma texana [66] Heraclenin (40) H…”

Fast separation and determination of coumarins in Fructus cnidii extracts by CEC using poly(butyl methacrylate‐co‐ethylene dimethacrylate‐co‐[2‐(methacryloyloxy)ethyl] trimethylammonium chloride) monolithic columns

“…The modern pharmacological studies prove that isopimpinelline inhibited P450-mediated enzyme activities in vitro [14] and have the potential chemopreventive effects when administered in the diet [15]. Bergapten possesses antiinflammatory and analgesic activities [16], whereas imperatorin has chemopreventive effects on hepatitis and skin tumor and exhibits strong cytotoxic activity on human leukemia [17][18][19][20]. Osthole can prevent atherosclerosis and suppress the accumulation of hepatic lipid [21].…”