Anti-inflammatory effects mechanism

Suematsu, M., Suzuki, M., Miura, S., Miura, S., Suzuki, K., Hibi, T., Watanabe, M. and Tsuchiya (1987b). Sulfasalazine and its metabolites attenuate respiratory burst of leukocytes -a possible mechanism of anti-inflammatory effects. J. Clin. Lab. Immunol. 23, 31-33. 

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. 

Shen YC, Chen CF, Chiou WF. (2002) Andrographolide prevents oxygen radical prodnction by human neutrophils. Possible mechanisms involved in its anti-inflammatory effect. Br J Pharmacol 135 399 06. 

There is some evidence that bismuth subsalicylate can be effective in travelers diarrhea due to Escherichia coli and for nonspecific diarrhea by such mechanisms as binding bacterial toxins, bactericidal action and local anti-inflammatory effects. 

Mechanism of Action Clioquinol is a broad-spectrum antibacterial agent but the mechanism of action is unknown. Hydrocortisone is a corticosteroid that diffuses across cell membranes, forms complexes with specific receptors and further binds to DNA and stimulates transcription of mRNA (messenger RNA) and subsequent protein synthesis of various enzymes thought to be ultimately responsible for the anti-inflammatory effects of corticosteroids applied topically to the skin Therapeutic Effect Alters membrane function and produces antibacterial activity Pharmacokinetics Clioquinol may be absorbed through the skin in sufficient amounts. 

Mechanism of Action Aphenylalkanoicacid that produces analgesic and anti-inflammatory effect by inhibiting prostaglandin synthesis. Also relaxes the iris sphincter Therapeutic Effect Reduces the inflammatory response and intensity of pain. Prevents or decreases miosis during cataract surgery. 

Mechanism of Action An NSAID that inhibits prostaglandin synthesis. Also produces vasodilation by acting centrally on the heat-regulating center of the hypothalamus. Therapeutic Effect Produces analgesic and anti-inflammatory effects and decreases... 

Local anesthetics have poorly understood effects on inflammation at sites of injury, and these anti-inflammatory effects may contribute to improved pain control in some chronic pain syndromes. At the concentrations used in spinal anesthesia, local anesthetics can inhibit transmission via substance P (neurokinin-1), NMDA, and AMPA receptors in the secondary afferent neurons (Figure 26-1). These effects may contribute to the analgesia achieved by subarachnoid administration. Local anesthetics can also be shown to block a variety of other ion channels, including nicotinic acetylcholine channels in the spinal cord. However, there is no convincing evidence that this mechanism is important in the acute clinical effects of these drugs. High concentrations of local anesthetics in the subarachnoid space can interfere with intra-axonal transport and calcium homeostasis, contributing to potential spinal toxicity. 

The role of A3 adenosine receptors in modulating inflammatory responses was also confirmed in mice after its targeted deletion. Adenosine mediates an increase in cutaneous vascular permeability leading to extravasation of serum proteins as an important mechanism in the development of an inflammatory response. It turned out that this reaction is dependent on the presence of A3 adenosine receptors on mast cells as both A3 knockout mice and mice lacking mast cells showed no response (Tilley et al. 2000). Adenosine accomplishes mainly an anti-inflammatory effect which is generally assumed to be mediated by the A2A subtype (Sitkovsky et al. 2004). However, A3 agonists were also found to produce anti-inflammatory actions, for example by inhibiting neutrophil function. Such a contribution to inhibition of inflammation was recently confirmed in a comparison of A2A and A3 knockout mice (van der Hoeven et al. 2008). 

To explore the anti-inflammatory effect of synthetic A3AR agonists and to look at the mechanism of action mediated down-stream to receptor activation, in vitro and in vivo studies were conducted. 

Scheme 15.1 Molecular mechanism involved with the anti-inflammatory effect of A3AR agonists...

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