Arachidonic acid anti-inflammatory effects

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat the signs and symptoms of inflammation, particularly arthritic pain. - It is mainly through the inhibition of cyclooxygenases (COXs), key enzymes in prostaglandin (PG) biosynthesis from arachidonic acid, that NSAIDs exert their anti-inflammatory effect. 

Hinokitiol is a tropolone type natural compound isolated from the wood of Chymacyparis taiwanesis. The compound has been utilized as a natural antimicrobial agent in hair tonics, toothpastes, cosmetics and food supplements. Hinokitiol was evaluated on five different arachidonic acid metabolic pathways for the mechanism of action of anti-inflammatory effects. It has been found to be a potent inhibitor with IC50 values of 0.1 pM against platelet-type 12-LOX and 50 pM against leukocyte-type 12-LOX. It also inhibited soybean 5-LOX enzyme (IC50 = 17 pM). However, hinokitiol had almost no effects on COX-1 and COX-2 enzymes. Similar inhibition profiles were also observed on synthetic tropolone derivatives [168]. 

Arachidonic acid is stored mainly in phospholipids of cell walls, from which it is mobilised largely by the action of phospholipase. Glucocorticoids prevent the formation of arachidonic acid by inducing the synthesis of an inhibitory polypeptide called lipocortin-1 the capacity to inhibit the subsequent formation of both prostaglandins and leukotrienes, explains part of the powerful anti-inflammatory effect of glucocorticoids (for other actions, see p. 664). 

Arachidonic acid is further metabolised by cyclooxygenase (COX, also called PGH synthase), which changes the linear fatty acids into the cyclical structures of the prostaglandins. Norrsteroidal anti-inflammatory drugs (NSAIDs) act exert their anti-inflammatory effects by inhibiting COX. 

COX-2 [Cyclo-oxygenase-2] An enzyme that catalyzes the synthesis of prostaglandins from the polyunsaturated fatty acid arachidonic acid. COX-2 is responsible for the production of prostaglandins attributable to stimulation (i.e., levels are induced in times of inflammation). Cyclooxygenase activity is inhibited by aspirin-like drugs, accounting for their anti-inflammatory effects. 

Used in folk medicine of Brazil to treat inflammation, pain, and urinary tract and other infections. Important anti-inflammatory effects of hydroethanolic extract (HEGG) and both biflavonoids through interaction with different intracellular signaling pathways, without interfering with the formation of arachidonic acid metabolites. 

Triterpenes are widely distributed in plants, and in many cases are the principles responsible for their anti-inflammatory effects. Many of these compounds are active in different in vivo experimental models such as hind paw edema induced by carrageenan, serotonin and phospholipase A2 ear edema induced by phorbol and daphnane esters, ethylphenylpropiolate, arachidonic acid and capsaicin adjuvant arthritis and experimental models of allergy. Other effects have been studied in vitro, and some triterpenes are active against inflammatory enzymes like 5-lipoxygenase, elastase and phospholipase A2. Others inhibit histamine, collagenase and interleukin release, lipid peroxidation and free radical-mediated processes, metabolism of endogenous corticoids, and complement and protein-kinase activities. 

A substantial body of literature exists reporting the inflammatory (or anti-inflammatory) effects of n-6 and n-3 PUFA. LA and ALA undergo a series of desaturation and elongation steps that yield arachidonic acid (AA, 20 4n-6) and EPA (20 5n-3), respectively. Additional metabolism of EPA produces the n-3 PUFA DHA (22 6n-3). However, the conversion of ALA to EPA, and especially DHA, is limited in humans (Goyens et al., 2005 Hussein et al., 2005 Pawlosky et al., 2001). Based on a metabolic model, Goyens et al. (2005) estimated that 7% of dietary ALA is converted to long-chain PUFA 99% is converted to EPA and 1% to docosapentaenoic acid (DPA). DHA is subsequently produced via elongation and desaturation of DPA. Ilierefore,... 

Shoeb M and Ramana KV. Anti-inflammatory effects of benfotiamine are mediated through the regulation of the arachidonic acid pathway in macrophages. Free Radical Biol Med 52 182-190 (2012). 

The release of arachidonic acid is stimulated in response to trauma (tissue damage). It is believed that the anti-inflammatory effects of adrenocortical steroids derive from their ability to suppress the enzymes that cause the release of arachidonic acid, thereby preventing the biosynthesis of prostaglandins. 

Based on previous reports of antiinflammatory activity, a 1989 double-blind, placebo-controlled, randomized study evaluated the effect of dried leaves (70-86 mg) in the treatment of rheumatoid arthritis. Over the 6-week trial, 41 female patients with symptomatic rheumatoid arthritis received feverfew or placebo. More than 13 laboratory and/ or clinical parameters were assessed. The authors concluded that there were no important differences between the control group and those receiving feverfew. Participating patients, however, had not previously responded to conventional therapies. The results do not preclude possible benefits for the use of feverfew in osteoarthritis and soft tissue lesions. Later in vivo studies showed that both feverfew extract and parthenolide possessed antiinflammatory and antinociceptive activities in mice and rats and that such activities were dose dependent. The extract, parthenolide, and some of the constituent flavonoids were also shown to inhibit the arachidonic acid pathways in leukocytes. Another possible mechanism for the anti-inflammatory effect of feverfew is the inhibition of the expression of intercellular adhesion molecule-1 (ICAM-1). ... 

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