Pge2

Figure 2 Biosynthesis of the prostaglandins.

The biosynthesis of prostaglandins consists of many steps that involve a variety of enzymes and co-factors. Inhibitions of prostaglandin synthesis may occur by blocking any of the steps involved in the biosynthesis. Prostaglandins display a wide range of biological effects in concentrations as low as 109 . They all are biologically active compounds. The action of E, F and A series are often dissimilar and sometime opposite. The biological activities of prostaglandins were of academic interest till 1971 when Vane and his co-workers demonstrated that prostaglandins play a crucial role in causing inflammation. It was demonstrated that prostaglandins have the ability to suppress the enzyme cyclo-oxygenase and thereby arrest the production of prostaglandins. This finding drew the attention of several scientists and prostaglandins study snowballed at a very fast pace. Among the prostaglandins the PGE2, PGD2 and PGF2 are mainly involved in the manifestation of inflammation, pain and swelling. These prostaglandins are also involved in causing fever. Although PGs have been found to be chemical indicator in several abnormalities the predominant use of E type PGs has been found in the treatment of peptic ulcer and cardiovascular diseases. The F type PGs are useful in the treatment of gynaecological disorders or fertility regulation. To date, the only widely marketed PGE analogue is misoprostol (27) used to prevent gastroduodenal ulcers caused by non-steroidal antiinflammatory drugs. Prostaglandin E: is involved in protecting the lining of the stomach. Misoprostol mimicks the action of prostaglandin E: in the body. It is used in the treatment of gastro-intestinal ulcers including those occurring in people who are taking one of a group of medicines known as non-steroidal antiinflammatory drugs (NSAIDs) to manage their arthritis. One of the adverse effects of NSAIDs is stomach and duodenal ulcers (gastrointestinal ulceration). Unfortunately misoprostol also mimicks the labour-inducing effects of prostaglandin E1. Therefore, women who are pregnant or who may become pregnant should avoid taking misoprostol as it may cause contraction of the uterus.28 PGF compounds have been found of limited utility in human reproductive regulations. However, they are more extensively used for farm animal estrus synchronization.

Prostaglandins are susceptible to air oxidation like any other polyunsaturated fatty acid derivatives. The F type prostaglandins are the most stable ones. The E type prostaglandins are very labile towards bases, and also get dehydrated under acidic conditions. Under basic conditions all E to A prostaglandins undergo for dehydration and also undergo for the isomerisation to the B-type prostaglandins. Mammalian prostaglandins occur in minute quantities. In 1969, Weinheimer and Spraggins29 reported the first high yield isolation of nonmammalian type, (15R)-PGA2 (28) and its methyl ester acetate (29) from the Caribbean gorgonea Plexaura homomalla (Esper). This report stimulated a worldwide search of PGs in marine life. Subsequently it was found that some forms of P. homomalla contained various mammalian-type PGs, such as (15S)-PGA2 (32), PGE2 (3), 13-14-cis-PGA2, 15-acetate, 13,14-dihydro-PGA2. Later on by monitoring the activity towards isolated guinea-pig ileum, PGF2 (6) was isolated from the Japanese coastal gorgonean, Euplexaura erecta.30 The occurrence of PGs in marine life other than gorgoneans was also reported, PGE2 (3) and PGF2 (6) are even isolated from the Australian red alga Gracilaria lichienoides.31 This was the first report of

the occurrence of PGs in plant. The red soft coral Lobophyton depressum32 was found to contain PGF2 (6) 11-acetate methyl ester and its 18-acetoxy derivative as well as their two corresponding free carboxylic acid. The Hawaiian octocoral Telesto nisei,33 which lacks symbiotic photosynthetic algae, yielded a series of highly functionized halogenated prostaglandins named punaglandins. The Okinawan soft coral (Stolonifer) Clavularia viridis Guoy and Gaimard (Stolonifera clavulariidae)34 afforded a number of prostaglandins name claviridenones.

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Arthritis Relief and Prevention

Arthritis Relief and Prevention

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