Inflammatory effect inhibition

Arterioles constriction (only slight in coronary and cerebral) Arterioles dilatation (p ) Bronchi (Pj) relaxation Anti-inflammatory effect inhibition of release of autacoids (histamine, leukotrienses) from mast cells, e g. asthma in type 1 allergy... 

The antiplatelet action of aspirin results from the fact that inhibition of thromboxane synthesis is essentially permanent in platelets they lack the machinery for new protein synthesis. In contrast, inhibition of prostacyclin synthesis in the vascular endothelium is temporary because these cells can synthesize new enzyme. Inhibition of prostaglandin synthesis also results in important anti-inflammatory effects. Inhibition of synthesis of fever-inducing prostaglandins in the brain produces the antipyretic action of NSAIDs. Closure of a patent ductus arteriosus in an otherwise normal infant can be accelerated with a potent NSAID such as indomethacin. 

Methylxanthines have relaxing and anti-inflammatory effects. Accumulation of intracellular cAMP by inhibition of PDE3 (phosphodiesterase-3) relaxes airway... 

The anti-inflammatory effects of the NSAIDs are carried out by inhibition of COX-2. The gastrointestinal adverse reactions are caused by inhibition of COX-1. The newer NSAIDs (celecoxib and rofecoxib) appear to work by specifically inhibiting the COX-2 enzyme, without inhibiting the COX-1 enzyme. Celecoxib and rofecoxib relieve pain and inflammation with less potential for gastrointestinal adverse... 

Pallapies, D., Peskar, B.A. and Peskar, B.M. (1992). 5-Aminosalicylic acid (5-ASA) inhibits the activity of nitric oxide (NO) contribution to its anti-inflammatory effects Gastroenterology 102, A677. 

The purported prophylactic use of Japanese herbal medicines to combat neuronal ageing has been related to their free-radical scavenging activity (Hiramatsu a al., 1992). Inhibition of the pro-inflammatory effects of cytokine interleukin-1 by recombinant endogenous interleukin-1 receptor antagonist in experimental rats is associated with alleviation of excitotoxic neuronal damage, an action which has also been related to the antiinflammatory effect of lipocortin 1 (Relton and Roth well, 1992). 

The structure-activity relation of triterpene QMs on the anti-inflammatory effect has been investigated with a series of analogues by comparing inhibition of the IL-1 (3 production in the LPS-induced monocytes.93-94 Clearly, the conjugated QM structure with alkenes is essential for the observed inhibition, and similar inhibitory effect was found with derivatives that are capable to form the conjugated QM through hydrolysis and/or oxidation.93-94 Also, the presence of the E ring in the triterpene QM structure is an additional contributor. 

NSAIDs are classified as non-selective (they inhibit COX-1 and COX-2) or selective (they inhibit only COX-2) based on degree of cyclooxygenase inhibition. COX-2 inhibition is responsible for anti-inflammatory effects, while COX-1 inhibition contributes to increased GI and renal toxicity associated with non-selective agents. Since the antiplatelet effect of non-selective NSAIDs is reversible, concurrent use may reduce the... 

In contrast, the COX-2 enzyme is not produced normally in most tissues, but its production is increased rapidly in the presence of inflammation and local tissue injury. This leads to the synthesis of prostaglandins involved in pain and inflammation. Consequently, blocking the COX-2 enzyme results in analgesic and anti-inflammatory effects. The beneficial effects of NSAIDs in reducing pain, decreasing joint stiffness, and improving function in patients with OA are thought to be due to inhibition of the COX-2 isoenzyme. 

Colchicine has a long history of successful use and was the treatment of choice for many years. It is used infrequently today because of its low therapeutic index. Colchicine is thought to exert its anti-inflammatory effects by interfering with the function of mitotic spindles in neutrophils by binding of tubulin dimers this inhibits phagocytic activity. 

Red wine contains quercetin, rutin, catechin, and epicatechin, among other flavonoids (Frankel and others 1993). Quercetin and other phenolic compounds isolated from wines were found to be more effective than a-tocopherol in inhibiting copper-catalyzed LDL oxidation. It has been determined that quercetin has also several anti-inflammatory effects it inhibits inflammatory cytokine production (Boots and others 2008), inducible NO synthase expression and activation of inflammatory transcription factors (Hamalainen and others 2007), and activity of cyclooxygenase and lipooxygenase (Issa 2006), among others. 

Hamalainen M, Nieminen R, Vuorela P, Heinonen M and Moilanen E. 2007. Anti-inflammatory effects of flavonoids genistein, kaempferol, quercetin and daidzein inhibit STAT-1 and NF-kB activations whereas flavones, isorhamnetin, naringenins, and pelargonidin inhibit only NF-kB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophagues. Mediators Inflamm 2007 45673. 

A variety of biochemical and molecular mechanisms have been described to explain how PUFAs can modulate immune cell fate and function. The primary mechanism of action of dietary n-3 PUFAs involves the replacement of AA in the lipid membrane of the cells with either EPA or DHA. This, in effect, competitively inhibits the oxygenation of AA by the COX enzymes. For example, the EPA-induced suppression in the production of AA-derived eicosanoids is followed by a subsequent increase in the production of those from EPA. Generally, the EPA-derived eicosanoids are considered to be much less potent than those from AA, thus explaining, at least partially, the anti-inflammatory effects of PUFAs. A similar mechanism of action can be demonstrated for DHA, either directly or by retroconversion to EPA. 

Detailed mechanistic studies have shown that FTY720 effectively inhibits the egress of T-cells [35] and B-cells [36] from lymph nodes, thereby reducing the number of activated cells that recirculate to peripheral inflammatory tissues [7,37], Two different hypotheses have been proposed to explain these effects. 

Inhibitors of Tpl-2 (MKKK), MEK1/2 (MKK1/2) and ERK1/2 have been reported. Macrophages from Tpl-2 knockout mice lack ERK1/2 activation leading to loss of TNFa expression and are insensitive to LPS-induced endotoxin shock [9]. Inhibition of Tpl-2 and MEK1/2 produces potent anti-inflammatory effects in cellular and animal models. 

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