Arachidonic acid inhibition

Mechanism of Action A salicylic acid derivative that locally inhibits arachidonic acid metabolite production, which is increased in patients with chronic inflammatory bowel disease. Therapeutic Effect Blocks prostaglandin production and diminishes inflammation in the colon. 

Only little information is available as to the role of arachidonic acid derivatives in VIP-stimulated PRL release. As in the case of TRH, agents that inhibit arachidonic acid generation blunt the PRL response to VIP [122]. 

Berbamine was found to inhibit arachidonic acid-induced inflammation in mice. Topical application of berbamine (2 pmol/mouse) markedly suppressed the tumor-promoting effect of 12-0-tetradecanoy lphorbol-13-acetate (1 pg) in mouse skin initiated with 7,12-... 

Berberine (0.50 mol/1) was found to dose-dependently inhibit collagen-, ADP-, and arachidonic acid-induced thromboxane A2 release from platelets and to inhibit platelet aggregation. Intravenous administration of the alkaloid (25 mg/kg) resulted in a lowered plasma level of prostaglandin I2 from 0.92 to 0.61 ng/m after one hour. These results suggest that berberine inhibits arachidonic acid metabolism, and that this effect may be an important factor in the antiaggregatory action of the alkaloid [252]. 

DEC also possesses action on the neuromuscular system of the parasites. Thus the killing of the microfilariae of O.volvulus by DEC may be a sequel of neuromuscular inhibition and "host reaction" against the parasite [121]. Recently Agrawal et al. [122] have shown that DEC is a potent inhibitor of ATPase of S. cervi in vitro. Liu and Weller [123] believe that the action of DEC may be due to the ability of the drug to inhibit arachidonic acid biosynthesis in the filariids. 

Antiplatelet Aggregation Activity. Alkaloids from Annonaceous plants were reported to inhibit platelet aggregation. According to our previous studies, more than twenty compounds were examined and most of the alkaloids were found inhibiting arachidonic acid (A.A) induced platelet aggregation [41]. Phenanthrene-alkaloids inhibited platelet aggregation initiated by four inducers (arachidonic acid, PAF, collagen, and thrombine)... 

The antioxidant actions of flavonoids appear to be involved in their observed antithrombotic action [50-52]. The antithrombotic and vasoprotective actions of quercetin, rutin, and other flavonoids have been attributed to their ability to bind to platelet membranes and scavenge free radicals [50]. In this manner, flavonoids restore the biosynthesis and action of endothelial prostacyclin and endothelialderived relaxing factor (EDRF), both of which are known to be inhibited by free radicals [50, 53, 54]. However, some flavonoids may inhibit arachidonic acid metabolism and platelet function by flavonoid-enzyme interactions rather than by antioxidant effects [55]. In addition to their antiaggregatory effects, flavonoids appear to increase vasodilation by inducing vascular smooth muscle relaxation, which may be mediated by inhibition of protein kinase C, PDFs, or by decreased cellular uptake of calcium [56]. 

Rybicki, J.P., Venton, D.L. and LeBreton, G.C. (1983). The thromboxane antagonist, 13-azaprostanoic acid, inhibits arachidonic acid-induced Ca release from isolated platelet membrane vesicles. Biochim. Biophys. Ada, 751, 66-73... 

Thyme essential oil inhibited arachidonic acid-induced platelet aggregation at a concentration of 7 jiM, and ADP-induced aggregation at a concentration of 100 pM, but had no effect on U46619-induced aggregation (Tognolini et al. 2006). The compound thymol inhibited platelet aggregation induced by collagen, ADP, arachidonic acid, and thrombin (Okazaki et al. 2002). 

A number of 7 oxabicyclo[2.2.1]heptane prostaglandin analogues were synthesized and evaluated as potential thromboxane synthetase inhibitors or thromboxane antagonists. Several of the compounds tested were shown to be TXA2 antagonists, judged from platelet aggregation and thromboxane inhibition tests. Two of the compounds also inhibited arachidonic acid induced bronchoconstriction [266]. 

Extracts from onion and garlic inhibit arachidonic acid metabolism in platelets. The exact nature of the inhibiting factor and the mechanism is not fully understood [396,397]. 

The Wittig methodology applied to the synthesis of 7.162 can be used in a variety of situations. Aldehyde 7.165, for example, was converted to 7.166 [methyl 8-(2-N-benzenesulfonylamino-l-cyclopentyl)oct-6-enoate] via a Wittig reaction and diazomethane estetiHcation. The corresponding acid of 7.166 was converted to its sodium carboxylate, and was shown to inhibit arachidonic acid induced blood platelet aggregation in rabbits. A quite different approach converted anhydride 7.167 to 7.168. Note the similarity to cleavage of bicyclic derivatives in section 7.1.B (see 7.75 and 7.78). 

In the MDCK cells, treatment with iV-(4-hydroxyphenyl)retinamide did not inhibit arachidonic acid release, suggesting that the retinoid was possibly acting as a cyclooxygenase inhibitor. Whether this enzyme inhibition is related to the retinoid character of the molecule or to a particular spatial configuration of the phenolic end group in the molecule is unknown certainly none of the bioassay systems described in Chapter 5, Vol. 1, point to a different role or mechanism of action for this retinoid as compared to retinoic acid. 

Currently, we are investigating the effect tea polyphenols on arachidonic acid release in intact cell system. This inhibitory effects are much more potent than on the inhibition of CPLA2. In addition to the inhibition of the catalytic activity of CPLA2, the tea polyphenols may inhibit arachidonic acid release in... 

Figure 2. Kinetics of basal (circles) and arachidonic acid-induced (diamonds) proton leak (A), and GDP-inhibited, arachidonic acid-induced proton leak (squares, B and C), in skeletal muscle mitochondria from control (open symbols)and heat-stressed (closed symbols) birds.

Azithromycin inhibits arachidonic acid release and prostaglandin E2 synthesis in LPS-stimulated J774A macrophages. Downstream effects include interference with the nuclear expression of activator protein-1 (AP-1) and NFkB. Azithromycin reduces IL-12p40 transcriptional activity by inhibiting the binding of AP-1 to the promoter site. The p40 subunit is a... 

Prostacyclin. Prostacyclin inhibits platelet aggregation and the release reaction. This involves binding to a specific membrane receptor, and a subsequent increase in cyclic AMP. In this respect prostacychn is 10 times more potent than PGD2 and 30 times more potent than PCEj. An increase in platelet cyclic AMP has been reported to inhibit arachidonic acid release from phospholipids, to inhibit cyclooxygenase and to have a direct inhibitory action on the contractile mechanism of the release reaction (Granstrom et al. 1982). 

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