Cycloxygenase inhibition

Resveratol is an antioxidant, anti-inflammatory, antiplatelet and antiallergy agent with demonstrated cancer-preventative activity (Cheong et al. 1999 Steele et al. 1998). It has been shown to inhibit cycloxygenase-2 (COX-2) in vitro (Subbaramaiah et al. 1998). 

Lipoxygenases (LOX), cycloxygenases (COXs), and xanthine oxidase (XO) are metalloen-zymes whose catalytic cycle involves ROS such as lipid peroxyl radicals, superoxide, and hydrogen peroxide. LOXs and COXs catalyze important steps in the biosynthesis of leuco-trienes and prostaglandins from arachidonic acid, which is an important cascade in the development of inflammatory responses. XO catalyzes the ultimate step in purine biosynthesis, the conversion of xanthine into uric acid. XO inhibition is an important issue in the... 

The discovery that a subtype cycloxygenase enzyme, COX-2, does not inhibit the formation of stomach-protecting prostaglandins paved the way for a series of NSAIDS whose stracmres depart markedly from the carboxylic acid-based drugs... 

Flunixin is registered or is under development in many countries for use in horses, cattle, and swine for treatment of equine colic, musculoskeletal disorders, acute endotoxin-induced mastitis in cattle, and respiratory disease (89-91). It is administered orally or parenterally for a maximum of 5 successive days (92). Flunixin is a genotoxic but not carcinogenic compound. Its mechanism of action is believed to be via the inhibition of cycloxygenase to reduce the presence of arachidonic acid metabolites produced during inflammation (93). 

As a class, PPs are considered active as antioxidant, antithrombogenic, and anti-inflammatory compounds. Many of them show an in vitro activity as scavengers of a wide range of RS, and also show inhibition of cycloxygenase and lipoxygenase (59,60), xantine oxidase (61), metalloproteases (62), and angiotensin II converting enzyme (63). All these activities are... 

Tetrahydro-2//-l,3,4-oxadiazin-2-ones <89EUP299449> and l-acyl-3-aryl-l//-4,l,2-benzoxa-diazines exhibit lipoxygenase inhibition <91EUP410834> the latter compounds are also cycloxygenase inhibitors. 

It is widely known that cyclic nucleotides are involved in fundamental processes, which include those related to platelet aggregation. In this way, the inhibition of the enzyme phosphodiesterase could be one such mechanism through its effect on cAMP (Cyclic Adenosin Monophosphate) and cGMP (Cyclic Guanosine Monophosphate) [117], Another mechanism might involve inhibition of cycloxygenase, with a consequent depression of thromboxane A2 biosynthesis [115] as well as some influence on the inhibition of the intracellular mobilization of Ca2+ flux and its influx across the plasma membrane, as happens with genistein [118]. 

Decrease lipid eicosanoid and prostaglandin (PG) generation by inhibiting the production of cytokines which specifically induce cycloxygenase-II in inflammatory cells. 

Subbaramaiah, K., Michaluart, R, Chung, W. J. and Dannenberg, A. J. 1998, Resveratrol inhibits the expression of cycloxygenase-2 in human mammary and oral epithelial cells , Pharmaceutical Biology, 36 Supplement 35-43. 

Mulabagal V, Subbaraju GV, Rao CV, Sivaramakrishna C, Dewitt DL, Holmes D, Sung B, Aggarwal BB, Tsay HS, M Nair (2009) Withanolide sulfoxide from Aswagandhga roots inhibits nuclear transcription factor- kappa-B, cycloxygenase and tumor cell proliferation. Phytother Res 23 987-992... 

Alkynoic fatty adds are toxic. It is assumed that they interfere with the metaboKsm of Kpids and fatty adds and inhibit Kpoxygenases and cycloxygenases. 

---