Lipoxygenase inflammation role

Lastly, eicosanoids are important pro-inflammatory mediators derived from membrane metabolism. PLA2 plays a key role in the production of eicosanoids, derived from arachi-donic acid of the phospholipids contained in the cell membrane (40,41). As mentioned earlier, arachidonic acid is liberated from the membrane-bound phospholipids by several forms of PLA2 and is the substrate for COX-1, COX-2, and 12-lipoxygenases (LOX) involved in vascular inflammation. 

Besides 12-LOX in platelets, the 5-LOX isoforms are constitutive in neutrophils. Evidences indicate that LOXs are involved in inflammation diseases and in atherosclerosis. 5-LOX is the enzyme that catalyzes the formation of leukotrienes with potential role for leukocytes and platelets interaction and inflammation. After platelet and leukocyte stimulation, products of both COX-1 and 5-LOX pathways increase. COX-1 activity derivatives increase the vascular permeability mediated by prostaglandins and produce platelet aggregation mediated by TXA2. The product of the lipoxygenase pathway, 5-oxo-6,8,1 1,14-eicosatetraenoic acid (5-Oxo-ETE), induces leukocyte chemotaxis and inflammation. 5-Oxo-ETE is formed by the oxidation of 5S-hydroxy-ETE (5-HETE) by 5-hydroxyeicosanoid dehydrogenase (5-HEDH), a microsomal enzyme found in leukocytes and platelets (42). 

There are many articles that address the role of St. John s wort in inflammation. As previously mentioned, St. John s wort is an inhibitor of IL-6, which is an important cytokine involved in inflammation (14,15). Additionally, hyperforin was found to inhibit cyclooxygenase (COX)-1 and 5-lipoxygenase (5-LO), key enzymes in the formation of proinflammatory eicosanoids. Moreover, it inhibited both enzymes at IC50 concentrations of 0.09 to 3 pM, which is close to the plasma concentrations achieved with standard dosing. Hyperforin was three times more potent then aspirin in its ability to inhibit COX-1 and almost equipotent to zileuton in its ability to inhibit 5-LO. Hyperforin did not significantly inhibit COX-2, 12-LO, or 15-LO enzymes (32). St. John s wort s ability to act as a 5-LO inhibitor could lead to a future role in asthma. 

Jatrorrhizine was found to possess anti-inflammatory activity as measured in the cobra venom factor-induced (CVF) rat paw edema. CVF edema was used to examine jatrorrhizine and other substances in order to detect novel compounds, since it has been shown that joint cyclooxygenase and lipoxygenase inhibitors, as well as immunoreactive drugs, exhibit more pronounced inhibitory effects on CVF in comparison to carrageenin-induced edema. CVF edema is dependent on activation of the complement system which plays an important role in acute and chronic inflammatory reactions, mediating the activity of immune complexes. This test system represents a functionally new type of acute inflammation via activation of the alternative complement pathway [290]. 

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