Inflammation is a fundamental biological response essential for protecting the body against pathogens and tissue injury.However, when dysregulated, it contributes to the development of chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis, substantially impairing quality of life and increasing the global healthcare burden. 1 Amidst the multiplicity of molecular agents involved in inflammation, activated B-cell nuclear factor kappa-light-chain enhancer (NF-κB) emerges as a key transcription factor that orchestrates the expression of numerous genes involved in inflammatory processes. 2spite its critical role, NF-κB remains an underexplored therapeutic target, partly due to the complexity of its signaling pathways and concerns about potential side effects. 3Since the early 20th century, anti-inflammatory pharmacology has focused predominantly on inhibiting cyclooxygenase enzymes (COX-1 and COX-2), a strategy that, while effective, is inherently limited by adverse gastrointestinal and cardiovascular effects. 4,5 contrast, NF-κB, despite regulating key inflammatory genes, including COX-2, remains a therapeutic target of remarkable potential that is still insufficiently explored in clinical pharmacology. 2,6is letter argues that the slow translation of NF-κB biology into drug development represents a significant gap in pharmaceutical innovation.The development of nonsteroidal anti-inflammatory drugs (NSAIDs) has been a mainstay of modern medicine for over a century, with their efficacy largely attributed to the inhibition of cyclooxygenase enzymes (COX-1 and COX-2) and, consequently, to the reduction of prostaglandin synthesis. 7,8is approach has revolutionized the management of pain and inflammation, but it is not without limitations.Chronic use of NSAIDs is associated with a significant burden of adverse effects, notably gastrointestinal (such as ulcers and bleeding) and cardiovascular (increased risk of thrombotic events), which restrict their long-term applicability and safety. 5erefore, the search for safer and more effective anti-inflammatory drugs remains an undeniable priority in pharmaceutical research. 9In parallel, nuclear factor kappa B (NF-κB) has emerged as a master regulator of the inflammatory response, orchestrating the expression of hundreds of pro-inflammatory genes, including cytokines, chemokines, adhesion molecules, and even COX-2 itself. 2,
Sousa et al. (Tue,) studied this question.