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pain, dysmenorrhea, and fever. COX is a microsomal enzyme that converts arachidonic acid into the prostaglandin. It is a common molecular target of several antiinflammatory drugs like aspirin, indomethacin, and ibuprofen. Three members of
COX enzymes are identified: COX1, COX2, and COX3 (Rouzer and Marnett 2009).
COX1 is constitutively expressed in most of the tissues and produces antiinflammatory prostaglandins protecting the gastrointestinal tract, kidneys, and liver.
Therefore, COX1 inhibitors may adversely affect these organs. COX2 enzyme
emerged as the potential therapeutic target with lesser gastrointestinal side effects.
COX2 is responsible for the formation of proinflammatory prostanoids and is the
prominent enzyme with proinflammatory function. The traditional NSAIDs are
known to inhibit both isoforms of COX (1 and 2), which imparts grave side effects
on the gastrointestinal tract and cardiovascular system. However, the development
of selective COX2 inhibitors like celecoxib 3 (Celebrex) and rofecoxib 4 (Vioxx®)
has enabled more safety and potential anti-inflammatory activity. Treatment with
COX2 inhibitors has been implemented to ameliorate hyperimmune response
underlying many autoimmune, inflammatory, and hypersensitive diseases. They are
found effective in managing pain and inflammation associated with rheumatoid
arthritis and osteoarthritis. However, drugs based on inhibition of COX2 exhibit
many side effects, including cardiovascular complications that limit their use in ailments. Therefore, the development of potentially effective, safe, and economical
therapy for treating inflammatory conditions is on high demand. COX2 induction
appears to be mediated by cytokines (IL-1, TNF-α) and growth factors (FGF, PDGF,
EGF). Some of the COX2 inhibitors are found to modulate immune response by
regulating a variety of cytokines such as IFN-γ and IL-10 production (Ni et al.
2007) and modulating TH1 and TH2 activity (Wu et al. 2008). Many COX2 inhibitors are therefore considered for treating autoimmune disorders like systemic lupus
erythematosus (Zhang et al. 2007).
10.7.2 PLA 2 Inhibitors
Enzymes PLA2 are involved in biosynthesis of arachidonic acid from membranebound phospholipids, and their inhibitors could perform as potential antiinflammatory agents. PLA 2 is involved in the biosynthesis of the potent inflammatory
mediator platelet-derived factor, and promotes the production and release of a variety of cytokines and hence is implicated in many inflammatory diseases and in
cancer (Lam et al. 1988). Selective PLA 2 enzyme inhibitor or its receptor antagonists have been proved to have promising anti-inflammatory properties against
inflammatory diseases, including rheumatoid arthritis, lung inflammation, multiple
sclerosis (MS), atherosclerosis, and cancer as well, where the apparent undesired
and hyperimmune response acts as the major obstacle for effective treatment (See
Chap. 9).
10 Anti-inflammatory Molecules: Immune System Mediators
pain, dysmenorrhea, and fever. COX is a microsomal enzyme that converts arachidonic acid into the prostaglandin. It is a common molecular target of several antiinflammatory drugs like aspirin, indomethacin, and ibuprofen. Three members of
COX enzymes are identified: COX1, COX2, and COX3 (Rouzer and Marnett 2009).
COX1 is constitutively expressed in most of the tissues and produces antiinflammatory prostaglandins protecting the gastrointestinal tract, kidneys, and liver.
Therefore, COX1 inhibitors may adversely affect these organs. COX2 enzyme
emerged as the potential therapeutic target with lesser gastrointestinal side effects.
COX2 is responsible for the formation of proinflammatory prostanoids and is the
prominent enzyme with proinflammatory function. The traditional NSAIDs are
known to inhibit both isoforms of COX (1 and 2), which imparts grave side effects
on the gastrointestinal tract and cardiovascular system. However, the development
of selective COX2 inhibitors like celecoxib 3 (Celebrex) and rofecoxib 4 (Vioxx®)
has enabled more safety and potential anti-inflammatory activity. Treatment with
COX2 inhibitors has been implemented to ameliorate hyperimmune response
underlying many autoimmune, inflammatory, and hypersensitive diseases. They are
found effective in managing pain and inflammation associated with rheumatoid
arthritis and osteoarthritis. However, drugs based on inhibition of COX2 exhibit
many side effects, including cardiovascular complications that limit their use in ailments. Therefore, the development of potentially effective, safe, and economical
therapy for treating inflammatory conditions is on high demand. COX2 induction
appears to be mediated by cytokines (IL-1, TNF-α) and growth factors (FGF, PDGF,
EGF). Some of the COX2 inhibitors are found to modulate immune response by
regulating a variety of cytokines such as IFN-γ and IL-10 production (Ni et al.
2007) and modulating TH1 and TH2 activity (Wu et al. 2008). Many COX2 inhibitors are therefore considered for treating autoimmune disorders like systemic lupus
erythematosus (Zhang et al. 2007).
10.7.2 PLA 2 Inhibitors
Enzymes PLA2 are involved in biosynthesis of arachidonic acid from membranebound phospholipids, and their inhibitors could perform as potential antiinflammatory agents. PLA 2 is involved in the biosynthesis of the potent inflammatory
mediator platelet-derived factor, and promotes the production and release of a variety of cytokines and hence is implicated in many inflammatory diseases and in
cancer (Lam et al. 1988). Selective PLA 2 enzyme inhibitor or its receptor antagonists have been proved to have promising anti-inflammatory properties against
inflammatory diseases, including rheumatoid arthritis, lung inflammation, multiple
sclerosis (MS), atherosclerosis, and cancer as well, where the apparent undesired
and hyperimmune response acts as the major obstacle for effective treatment (See
Chap. 9).
10 Anti-inflammatory Molecules: Immune System Mediators