Cyclooxygenase-2 Inhibitors as a Therapeutic Target in Inflammatory Diseases

Abstract

Inflammation plays a crucial role in the development of many complex diseases and disorders including autoimmune diseases, metabolic syndrome, neurodegenerative diseases, and cardiovascular pathologies. Prostaglandins play a regulatory role in inflammation. Cyclooxygenases are the main mediators of inflammation by catalyzing the initial step of arachidonic acid metabolism and prostaglandin synthesis. The differential expression of the constitutive isoform COX-1 and the inducible isoform COX-2, and the finding that COX-1 is the major form expressed in the gastro-intestinal tract, lead to the search for COX-2-selective inhibitors as anti-inflammatory agents that might diminish the gastrointestinal side effects of traditional non-steroidal anti-inflamatory drugs (NSAIDs). COX-2 isoform is expressed predominantly in inflammatory cells and decidedly upregulated in chronic and acute inflammations, becoming a critical target for many pharmacological inhibitors. COX-2 selective inhibitors happen to show equivalent efficacy with that of conventional NSAIDs, but they have reduced gastrointestinal side effects. This review would elucidate the most recent findings on selective COX-2 inhibition and their relevance to human pathology, concretely in inflammatory pathologies characterized by a prolonged pro-inflammatory status, including autoimmune diseases, metabolic syndrome, obesity, atherosclerosis, neurodegenerative diseases, chronic obstructive pulmonary disease, arthritis, chronic inflammatory bowel disease and cardiovascular pathologies.

Laminar Inflammation Responses in the Oligofructose Overload Induced Model of Bovine Laminitis

“…Similar results were reported in OF-induced equine laminitis, indicating that these inflammatory molecules might play similar roles in the two laminitis models (18). COX-2 is known as a crucial mediator in the inflammatory response, as the various physiological effects of numerous prostanoids (the products downstream of COX-2), including platelet aggregation, vasomotor, and proinflammatory effects (59). As such, COX-2 is a therapeutic target for nonsteroidal anti-inflammatory drugs (NSAIDs).…”

Sex differences in nociceptor translatomes contribute to divergent prostaglandin signaling in male and female mice

“…Ptgds catalyzes the conversion of prostaglandin H 2 (PGH 2 ) to prostaglandin D2 (PGD 2 ) ( Figure 5A), which is known to be the most abundant prostaglandin in the brain (41, 42) and regulates nociception, sleep and temperature homeostasis (43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53). Prostaglandins are among the most widely studied of pain inducing molecules and many drugs are currently marketed as analgesics that target this class of molecules (54)(55)(56). We reasoned that previously unknown sex differences in prostaglandin signaling could have a dramatic impact on further our understanding of sex differences in pain.…”

Betanin as a multipath oxidative stress and inflammation modulator: a beetroot pigment with protective effects on cardiovascular disease pathogenesis

“…Betanin was more effective in inhibiting COX-2 than other phytochemicals, such as cyanidin-3-O-glycoside (anthocyanin), lycopene, chlorophyll, b-carotene and bixin. Since COX-2 is induced in injury and inflammation conditions, while COX-1 is constitutively expressed under physiological conditions in various tissues, catalyzing the cytoprotective prostaglandin biosynthesis (PGI 2 and PGE 2 ), mainly in the gastrointestinal system, the apparent selectivity of betanin over COX-2 resembles the COX-2 selective non-steroidal anti-inflammatory drugs (NSAIDs), which avoid the deleterious effects of unwanted COX-1 inhibition (gastrointestinal, renal and liver toxicity) (Ferrer et al 2019;Radi and Khan 2019;S€ uleyman, Demircan, and Karag€ oz 2007;Tai and McAlindon 2018;Cooper et al 2019).…”